Gene therapy for cancer: present status and future perspective

  • Magid Amer
Keywords: Adenoviruses, Clinical trials, Electroporation, Gene silencing, Gene transfer technique, Immunomodulation, Molecular targeted therapy, Oncolytic viruses, Retroviruses, Suicide transgenes

Abstract

Advancements in human genomics over the last two decades have shown that cancer is mediated by somatic aberration in the host genome. This discovery has incited enthusiasm among cancer researchers; many now use therapeutic approaches in genetic manipulation to improve cancer regression and find a potential cure for the disease. Such gene therapy includes transferring genetic material into a host cell through viral (or bacterial) and non-viral vectors, immunomodulation of tumor cells or the host immune system, and manipulation of the tumor microenvironment, to reduce tumor vasculature or to increase tumor antigenicity for better recognition by the host immune system. Overall, modest success has been achieved with relatively minimal side effects. Previous approaches to cancer treatment, such as retrovirus integration into the host genome with the risk of mutagenesis and second malignancies, immunogenicity against the virus and/or tumor, and resistance to treatment with disease relapse, have markedly decreased with the new generation of viral and non-viral vectors. Several tumor-specific antibodies and genetically modified immune cells and vaccines have been developed, yet few are presently commercially available, while many others are still ongoing in clinical trials. It is anticipated that gene therapy will play an important role in future cancer therapy as part of a multimodality treatment, in combination with, or following other forms of cancer therapy, such as surgery, radiation and chemotherapy. The type and mode of gene therapy will be determined based on an individual’s genomic constituents, as well as his or her tumor specifics, genetics, and host immune status, to design a multimodality treatment that is unique to each individual’s specific needs.

Downloads

Download data is not yet available.

References

Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C: Initial sequencing and analysis of the human genome. Nature. 2001, 409 (6822): 860-921. 10.1038/35057062.

PubMedGoogle Scholar

Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wortman JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N: The sequence of the human genome. Science (New York, NY). 2001, 291 (5507): 1304-1351. 10.1126/science.1058040.

Google Scholar

Dulbecco R: A turning point in cancer research: sequencing the human genome. Science (New York, NY). 1986, 231 (4742): 1055-1056. 10.1126/science.3945817.

Google Scholar

Strachan T, Read A: Gene therapy and other molecular genetic-based therapeutic approaches. Human Molecular Genetics. Edited by: Strachan T, Read AP. 1999, New York: Wiley-Liss, 2

Google Scholar

Miller AD: Retroviral vectors. Curr Top Microbiol Immunol. 1992, 158: 1-24.

PubMedGoogle Scholar

Weichselbaum RR, Kufe D:Gene therapy of cancer. Lancet. 1997, 349 (Suppl 2): SII10-2.

PubMedGoogle Scholar

DeVita VT, Rosenberg SA: Two hundred years of cancer research. N Engl J Med. 2012, 366 (23): 2207-2214. 10.1056/NEJMra1204479.

PubMedGoogle Scholar

Curie P, Curie M, Bémont G: On a new, strongly radioactive substance contained in pitchblende. CR (East Lansing, Mich). 1898, 127: 1215-1217.

Google Scholar

Lage H: Bacterial delivery of RNAi effectors. Gene Therapy of Cancer. Edited by: Lattime EC, Gerson SL. 2013, San Diego (CA): Elsevier, 67-75. 3

Google Scholar

Goodman LS, Wintrobe MM, Dameshek W, Goodman MJ, Gilman A, McLennan MT: Landmark article Sept. 21, 1946: nitrogen mustard therapy: use of methyl-bis(beta-chloroethyl)amine hydrochloride and tris(beta-chloroethyl)amine hydrochloride for Hodgkin's disease, lymphosarcoma, leukemia and certain allied and miscellaneous disorders by Louis S. Goodman, Maxwell M. Wintrobe, William Dameshek, Morton J. Goodman, Alfred Gilman and Margaret T. McLennan. JAMA. 1984, 251 (17): 2255-2261. 10.1001/jama.1984.03340410063036.

PubMedGoogle Scholar

Farber S, Diamond LK: Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid. N Engl J Med. 1948, 238 (23): 787-793. 10.1056/NEJM194806032382301.

PubMedGoogle Scholar

Hemminki O, Hemminki A: Oncolytic adenoviruses in the treatment of cancer in humans. Gene Therapy of Cancer. Edited by: Lattime EC, Gerson SL. 2013, San Diego (CA): Elsevier, 153-170. 3

Google Scholar

Kelly E, Russell SJ: History of oncolytic viruses: genesis to genetic engineering. Mol Ther. 2007, 15 (4): 651-659.

PubMedGoogle Scholar

Maloney DG, Grillo-Lopez AJ, White CA, Bodkin D, Schilder RJ, Neidhart JA, Janakiraman N, Foon KA, Liles TM, Dallaire BK, Wey K, Royston I, Davis T, Levy R: IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma. Blood. 1997, 90 (6): 2188-2195.

PubMedGoogle Scholar

Sheridan C: Gene therapy finds its niche. Nat Biotechnol. 2011, 29 (2): 121-128. 10.1038/nbt.1769.

PubMedGoogle Scholar

Chiocca EA, Abbed KM, Tatter S, Louis DN, Hochberg FH, Barker F, Kracher J, Grossman SA, Fisher JD, Carson K, Rosenblum M, Mikkelsen T, Olson J, Markert J, Rosenfeld S, Nabors LB, Brem S, Phuphanich S, Freeman S, Kaplan R, Zwiebel J: A phase I open-label, dose-escalation, multi-institutional trial of injection with an E1B-Attenuated adenovirus, ONYX-015, into the peritumoral region of recurrent malignant gliomas, in the adjuvant setting. Mol Ther. 2004, 10 (5): 958-966. 10.1016/j.ymthe.2004.07.021.

PubMedGoogle Scholar

Block SL, Nolan T, Sattler C, Barr E, Giacoletti KE, Marchant CD, Castellsague X, Rusche SA, Lukac S, Bryan JT, Cavanaugh PF, Reisinger KS, Protocol 016 Study Group: Comparison of the immunogenicity and reactogenicity of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in male and female adolescents and young adult women. Pediatrics. 2006, 118 (5): 2135-2145. 10.1542/peds.2006-0461.

PubMedGoogle Scholar

Kantoff PW, Schuetz TJ, Blumenstein BA, Glode LM, Bilhartz DL, Wyand M, Manson K, Panicali DL, Laus R, Schlom J, Dahut WL, Arlen PM, Gulley JL, Godfrey WR: Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol. 2010, 28 (7): 1099-1105. 10.1200/JCO.2009.25.0597.

PubMedCentralPubMedGoogle Scholar

Robinson DR, Wu YM, Vats P, Su F, Lonigro RJ, Cao X, Kalyana-Sundaram S, Wang R, Ning Y, Hodges L, Gursky A, Siddiqui J, Tomlins SA, Roychowdhury S, Pienta KJ, Kim SY, Roberts JS, Rae JM, Van Poznak CH, Hayes DF, Chugh R, Kunju LP, Talpaz M, Schott AF, Chinnaiyan AM: Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet. 2013, 45 (12): 1446-1451. 10.1038/ng.2823.

PubMedCentralPubMedGoogle Scholar

Toy W, Shen Y, Won H, Green B, Sakr RA, Will M, Li Z, Gala K, Fanning S, King TA, Hudis C, Chen D, Taran T, Hortobagyi G, Greene G, Berger M, Baselga J, Chandarlapaty S: ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet. 2013, 45 (12): 1439-1445. 10.1038/ng.2822.

PubMedCentralPubMedGoogle Scholar

Koboldt DC, Fulton RS, McLellan MD, Schmidt H, Kalicki-Veizer J, McMichael JF, Fulton LL, Dooling DJ, Ding L, Mardis ER, Wilson RK, Ally A, Balasundaram M, Butterfield YS, Carlsen R, Carter C, Chu A, Chuah E, Chun HJ, Coope RJ, Dhalla N, Guin R, Hirst C, Hirst M, Holt RA, Lee D, Li HI, Mayo M, Moore RA, Mungall AJ: Comprehensive molecular portraits of human breast tumours. Nature. 2012, 490 (7418): 61-70. 10.1038/nature11412.

Google Scholar

Shirley S, Heller R, Heller L: Electroporation gene therapy. Gene Therapy of Cancer. Edited by: Lattime EC, Gerson SL. 2013, San Diego (CA): Elsevier, 93-106. 3

Google Scholar

Baranyi L, Slepushkin V, Dropulic B: Ex vivo gene therapy: utilization of genetic vectors for the generation of genetically modified cell products for therapy. Gene Therapy of Cancer. Edited by: Lattime EC, Gerson SL. 2013, San Diego (CA): Elsevier, 3-18. 3

Google Scholar

Yuan Z, Pastoriza J, Quinn T, Libutti S: Targeting tumor vasculature using adeno-associated virus page vector coding tumor necrosis factor-a. Gene Therapy of Cancer. Edited by: Lattime EC, Gerson SL. 2013, San Diego (CA): Elsevier, 19-33. 3

Google Scholar

Zabner J, Fasbender AJ, Moninger T, Poellinger KA, Welsh MJ: Cellular and molecular barriers to gene transfer by a cationic lipid. J Biol Chem. 1995, 270 (32): 18997-19007. 10.1074/jbc.270.32.18997.

PubMedGoogle Scholar

Tagami T, Suzuki T, Matsunaga M, Nakamura K, Moriyoshi N, Ishida T, Kiwada H: Anti-angiogenic therapy via cationic liposome-mediated systemic siRNA delivery. Int J Pharm. 2012, 422 (1–2): 280-289.

PubMedGoogle Scholar

Yang W, Sun T, Cao J, Liu F: Survivin downregulation by siRNA/cationic liposome complex radiosensitises human hepatoma cells in vitro and in vivo. Int J Radiat Biol. 2010, 86 (6): 445-457. 10.3109/09553001003668006.

PubMedGoogle Scholar

Wagner E, Plank C, Zatloukal K, Cotten M, Birnstiel ML: Influenza virus hemagglutinin HA-2 N-terminal fusogenic peptides augment gene transfer by transferrin-polylysine-DNA complexes: toward a synthetic virus-like gene-transfer vehicle. Proc Natl Acad Sci U S A. 1992, 89 (17): 7934-7938. 10.1073/pnas.89.17.7934.

PubMedCentralPubMedGoogle Scholar

Soltani F, Sankian M, Hatefi A, Ramezani M: Development of a novel histone H1-based recombinant fusion peptide for targeted non-viral gene delivery. Int J Pharm. 2013, 441 (1–2): 307-315.

PubMedGoogle Scholar

Di Martino MT, Leone E, Amodio N, Foresta U, Lionetti M, Pitari MR, Cantafio ME, Gulla A, Conforti F, Morelli E, Tomaino V, Rossi M, Negrini M, Ferrarini M, Caraglia M, Shammas MA, Munshi NC, Anderson KC, Neri A, Tagliaferri P, Tassone P: Synthetic miR-34a mimics as a novel therapeutic agent for multiple myeloma: in vitro and in vivo evidence. Clin Cancer Res. 2012, 18 (22): 6260-6270. 10.1158/1078-0432.CCR-12-1708.

PubMedCentralPubMedGoogle Scholar

Soliman M, Nasanit R, Abulateefeh SR, Allen S, Davies MC, Briggs SS, Seymour LW, Preece JA, Grabowska AM, Watson SA, Alexander C: Multicomponent synthetic polymers with viral-mimetic chemistry for nucleic acid delivery. Mol Pharm. 2012, 9 (1): 1-13. 10.1021/mp200108q.

PubMedGoogle Scholar

Nie Y, Schaffert D, Rodl W, Ogris M, Wagner E, Gunther M: Dual-targeted polyplexes: one step towards a synthetic virus for cancer gene therapy. J Control Release. 2011, 152 (1): 127-134. 10.1016/j.jconrel.2011.02.028.

PubMedGoogle Scholar

Hackett PB, Largaespada DA, Switzer KC, Cooper LJ: Evaluating risks of insertional mutagenesis by DNA transposons in gene therapy. Transl Res. 2013, 161 (4): 265-283. 10.1016/j.trsl.2012.12.005.

PubMedCentralPubMedGoogle Scholar

Kwon S, Min J: Genetically engineered Salmonella typhimurium for targeted cancer therapy. Gene Therapy of Cancer. Edited by: Lattime EC, Gerson SL. 2013, San Diego (CA): Elsevier, 443-452. 3

Google Scholar

Benoit MR, Mayer D, Barak Y, Chen IY, Hu W, Cheng Z, Wang SX, Spielman DM, Gambhir SS, Matin A: Visualizing implanted tumors in mice with magnetic resonance imaging using magnetotactic bacteria. Clin Cancer Res. 2009, 15 (16): 5170-5177. 10.1158/1078-0432.CCR-08-3206.

PubMedCentralPubMedGoogle Scholar

Baban CK, Cronin M, O'Hanlon D, O'Sullivan GC, Tangney M: Bacteria as vectors for gene therapy of cancer. Bioeng Bugs. 2010, 1 (6): 385-394. 10.4161/bbug.1.6.13146.

PubMedCentralPubMedGoogle Scholar

Thomas CE, Ehrhardt A, Kay MA: Progress and problems with the use of viral vectors for gene therapy. Nat Rev Genet. 2003, 4 (5): 346-358. 10.1038/nrg1066.

PubMedGoogle Scholar

Kuroda S, Kagawa S, Fujiwara T: Selectively replicating oncolytic adenoviruses combined with chemotherapy, radiotherapy, or molecular targeted therapy for treatment of human cancers. Gene Therapy of Cancer. Edited by: Lattime EC, Gerson SL. 2013, San Diego (CA): Elsevier, 171-183. 3

Google Scholar

Wu E, Nemerow GR: Virus yoga: the role of flexibility in virus host cell recognition. Trends Microbiol. 2004, 12 (4): 162-169. 10.1016/j.tim.2004.02.005.

PubMedGoogle Scholar

Mathis JM, Stoff-Khalili MA, Curiel DT: Oncolytic adenoviruses - selective retargeting to tumor cells. Oncogene. 2005, 24 (52): 7775-7791. 10.1038/sj.onc.1209044.

PubMedGoogle Scholar

Zemp FJ, Corredor JC, Lun X, Muruve DA, Forsyth PA: Oncolytic viruses as experimental treatments for malignant gliomas: using a scourge to treat a devil. Cytokine Growth Factor Rev. 2010, 21 (2–3): 103-117.

PubMedGoogle Scholar

Balvers R, Gomez-Manzano C, Jiang H, Piya S, Klein S, Lamfers M, Driven C, Fueyo J: Advances on oncolytic virotherapy for brain tumors. Gene Therapy of Cancer. Edited by: Lattime EC, Gerson SL. 2013, San Diego (CA): Elsevier, 137-151. 3

Google Scholar

Kaliberova LN, Krendelchtchikova V, Harmon DK, Stockard CR, Petersen AS, Markert JM, Gillespie GY, Grizzle WE, Buchsbaum DJ, Kaliberov SA: CRAdRGDflt-IL24 virotherapy in combination with chemotherapy of experimental glioma. Cancer Gene Ther. 2009, 16 (10): 794-805. 10.1038/cgt.2009.23.

PubMedCentralPubMedGoogle Scholar

Nuesch JP, Lacroix J, Marchini A, Rommelaere J: Molecular pathways: rodent parvoviruses–mechanisms of oncolysis and prospects for clinical cancer treatment. Clin Cancer Res. 2012, 18 (13): 3516-3523. 10.1158/1078-0432.CCR-11-2325.

PubMedGoogle Scholar

White E, Gill S: Selectively replicating Herpes simplex viral vectors. Gene Therapy of Cancer. Edited by: Lattime EC, Gerson SL. 2013, San Diego (CA): Elsevier, 199-211. 3

Google Scholar

Sharp PM: Origins of human virus diversity. Cell. 2002, 108 (3): 305-312. 10.1016/S0092-8674(02)00639-6.

PubMedGoogle Scholar

Hu JC, Coffin RS, Davis CJ, Graham NJ, Groves N, Guest PJ, Harrington KJ, James ND, Love CA, McNeish I, Medley LC, Michael A, Nutting CM, Pandha HS, Shorrock CA, Simpson J, Steiner J, Steven NM, Wright D, Coombes RC: A phase I study of OncoVEXGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor. Clin Cancer Res. 2006, 12 (22): 6737-6747. 10.1158/1078-0432.CCR-06-0759.

PubMedGoogle Scholar

Liu TC, Zhang T, Fukuhara H, Kuroda T, Todo T, Canron X, Bikfalvi A, Martuza RL, Kurtz A, Rabkin SD: Dominant-negative fibroblast growth factor receptor expression enhances antitumoral potency of oncolytic herpes simplex virus in neural tumors. Clin Cancer Res. 2006, 12 (22): 6791-6799. 10.1158/1078-0432.CCR-06-0263.

PubMedGoogle Scholar

Bryson P, Wang P: Lentivector vaccines. Gene Therapy of Cancer. Edited by: Lattime EC, Gerson SL. 2013, San Diego (CA): Elsevier, 345-361. 3

Google Scholar

Breckpot K, Aerts JL, Thielemans K: Lentiviral vectors for cancer immunotherapy: transforming infectious particles into therapeutics. Gene Ther. 2007, 14 (11): 847-862. 10.1038/sj.gt.3302947.

PubMedGoogle Scholar

Hu B, Yang H, Dai B, Tai A, Wang P: Nonintegrating lentiviral vectors can effectively deliver ovalbumin antigen for induction of antitumor immunity. Hum Gene Ther. 2009, 20 (12): 1652-1664. 10.1089/hum.2009.012.

PubMedCentralPubMedGoogle Scholar

Michelini Z, Negri DR, Baroncelli S, Spada M, Leone P, Bona R, Klotman ME, Cara A: Development and use of SIV-based Integrase defective lentiviral vector for immunization. Vaccine. 2009, 27 (34): 4622-4629. 10.1016/j.vaccine.2009.05.070.

PubMedCentralPubMedGoogle Scholar

Comins C, Simpson G, Relph K, Harrington K, Melcher A, Pandha H: Reoviral therapy for cancer: strategies for improving antitumor efficacy using radio- and chemotherapy. Gene Therapy of Cancer. Edited by: Lattime EC, Gerson SL. 2013, San Diego (CA): Elsevier, 185-198. 3

Google Scholar

Pachnis V, Brannan CI, Tilghman SM: The structure and expression of a novel gene activated in early mouse embryogenesis. EMBO J. 1988, 7 (3): 673-681.

PubMedCentralPubMedGoogle Scholar

Matouk I, Raveh E, Ohana P, Lail RA, Gershtain E, Gilon M, De Groot N, Czerniak A, Hochberg A: The increasing complexity of the oncofetal h19 gene locus: functional dissection and therapeutic intervention. Int J Mol Sci. 2013, 14 (2): 4298-4316. 10.3390/ijms14024298.

PubMedCentralPubMedGoogle Scholar

Ohana P, Matouk I, Amit D, Gilon M, Hochberg A: Toxin-based cancer gene therapy under the control of oncofetal H19 regulatory sequences. Gene Therapy of Cancer. Edited by: Lattime EC, Gerson SL. 2013, San Diego (CA): Elsevier, 107-122. 3

Google Scholar

Li Y, McCadden J, Ferrer F, Kruszewski M, Carducci M, Simons J, Rodriguez R: Prostate-specific expression of the diphtheria toxin A chain (DT-A): studies of inducibility and specificity of expression of prostate-specific antigen promoter-driven DT-A adenoviral-mediated gene transfer. Cancer Res. 2002, 62 (9): 2576-2582.

PubMedGoogle Scholar

Fung H, Gersson S: Viral insertion site detection and analysis in cancer gene therapy. Gene Therapy of Cancer. Edited by: Lattime EC, Gerson SL. 2013, San Diego (CA): Elsevier, 35-46. 3

Google Scholar

Gujrati M, Lu Z: Targeted systemic delivery of therapeutic siRNA. Gene Therapy of Cancer. Edited by: Lattime EC, Gerson SL. 2013, San Diego (CA): Elsevier, 47-65. 3

Google Scholar

Sato Y, Murase K, Kato J, Kobune M, Sato T, Kawano Y, Takimoto R, Takada K, Miyanishi K, Matsunaga T, Takayama T, Niitsu Y: Resolution of liver cirrhosis using vitamin A-coupled liposomes to deliver siRNA against a collagen-specific chaperone. Nat Biotechnol. 2008, 26 (4): 431-442. 10.1038/nbt1396.

PubMedGoogle Scholar

Davis ME: The first targeted delivery of siRNA in humans via a self-assembling, cyclodextrin polymer-based nanoparticle: from concept to clinic. Mol Pharm. 2009, 6 (3): 659-668. 10.1021/mp900015y.

PubMedGoogle Scholar

Tabernero J, Shapiro GI, LoRusso PM, Cervantes A, Schwartz GK, Weiss GJ, Paz-Ares L, Cho DC, Infante JR, Alsina M, Gounder MM, Falzone R, Harrop J, White AC, Toudjarska I, Bumcrot D, Meyers RE, Hinkle G, Svrzikapa N, Hutabarat RM, Clausen VA, Cehelsky J, Nochur SV, Gamba-Vitalo C, Vaishnaw AK, Sah DW, Gollob JA, Burris HA: First-in-humans trial of an RNA interference therapeutic targeting VEGF and KSP in cancer patients with liver involvement. Cancer Discov. 2013, 3 (4): 406-417. 10.1158/2159-8290.CD-12-0429.

PubMedGoogle Scholar

Geng J, Xiao S, Zhang S, Liu C, Li Y, Ji J, Fang Z, Sun Y, Su X, Cai Y, Xu G, Li D, Zhu G, Xu B: Clinical effectiveness of recombinant adenovirus-p53 combined with radiotherapy in advanced soft tissue sarcoma: a report of 37 cases. J Clin Oncol. 2014, 32 (suppl; abstr e21514):

Google Scholar

Pan JJ, Zhang SW, Chen CB, Xiao SW, Sun Y, Liu CQ, Su X, Li DM, Xu G, Xu B, Lu YY: Effect of recombinant adenovirus-p53 combined with radiotherapy on long-term prognosis of advanced nasopharyngeal carcinoma. J Clin Oncol. 2009, 27 (5): 799-804. 10.1200/JCO.2008.18.9670.

PubMedGoogle Scholar

Lai SY, Koppikar P, Thomas SM, Childs EE, Egloff AM, Seethala RR, Branstetter BF, Gooding WE, Muthukrishnan A, Mountz JM, Lui VW, Shin DM, Agarwala SS, Johnson R, Couture LA, Myers EN, Johnson JT, Mills G, Argiris A, Grandis JR: Intratumoral epidermal growth factor receptor antisense DNA therapy in head and neck cancer: first human application and potential antitumor mechanisms. J Clin Oncol. 2009, 27 (8): 1235-1242. 10.1200/JCO.2008.17.8251.

PubMedCentralPubMedGoogle Scholar

Greenberger JS: Radioprotection. In Vivo. 2009, 23 (2): 323-336.

PubMedCentralPubMedGoogle Scholar

Cai Y, Bak RO, Mikkelsen JG: Targeted genome editing by lentiviral protein transduction of zinc-finger and TAL-effector nucleases. eLife. 2014, 3: e01911-

PubMedCentralPubMedGoogle Scholar

Uhde-Stone C, Sarkar N, Antes T, Otoc N, Kim Y, Jiang YJ, Lu B: A TALEN-based strategy for efficient bi-allelic miRNA ablation in human cells. RNA (New York, NY). 2014, 20 (6): 948-955. 10.1261/rna.042010.113.

Google Scholar

Sakuma T, Woltjen K: Nuclease-mediated genome editing: at the front-line of functional genomics technology. Develop Growth Differ. 2014, 56 (1): 2-13. 10.1111/dgd.12111.

Google Scholar

Cobleigh MA, Vogel CL, Tripathy D, Robert NJ, Scholl S, Fehrenbacher L, Wolter JM, Paton V, Shak S, Lieberman G, Slamon DJ: Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol. 1999, 17 (9): 2639-2648.

PubMedGoogle Scholar

McLaughlin P, Grillo-Lopez AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, Bence-Bruckler I, White CA, Cabanillas F, Jain V, Ho AD, Lister J, Wey K, Shen D, Dallaire BK: Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998, 16 (8): 2825-2833.

PubMedGoogle Scholar

Foon KA, Yang XD, Weiner LM, Belldegrun AS, Figlin RA, Crawford J, Rowinsky EK, Dutcher JP, Vogelzang NJ, Gollub J, Thompson JA, Schwartz G, Bukowski RM, Roskos LK, Schwab GM: Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody. Int J Radiat Oncol Biol Phys. 2004, 58 (3): 984-990. 10.1016/j.ijrobp.2003.09.098.

PubMedGoogle Scholar

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004, 350 (23): 2335-2342. 10.1056/NEJMoa032691.

PubMedGoogle Scholar

Glassman PM, Balthasar JP: Mechanistic considerations for the use of monoclonal antibodies for cancer therapy. Cancer Biol Med. 2014, 11 (1): 20-33.

PubMedCentralPubMedGoogle Scholar

Boon T, Van der Bruggen P: Human tumor antigens recognized by T lymphocytes. J Exp Med. 1996, 183 (3): 725-729. 10.1084/jem.183.3.725.

PubMedGoogle Scholar

Steinman RM, Banchereau J: Taking dendritic cells into medicine. Nature. 2007, 449 (7161): 419-426. 10.1038/nature06175.

PubMedGoogle Scholar

De Souza AP, Bonorino C: Tumor immunosuppressive environment: effects on tumor-specific and nontumor antigen immune responses. Expert Rev Anticancer Ther. 2009, 9 (9): 1317-1332. 10.1586/era.09.88.

PubMedGoogle Scholar

Gajewski TF, Schreiber H, Fu YX: Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 2013, 14 (10): 1014-1022. 10.1038/ni.2703.

PubMedCentralPubMedGoogle Scholar

Mlecnik B, Tosolini M, Kirilovsky A, Berger A, Bindea G, Meatchi T, Bruneval P, Trajanoski Z, Fridman WH, Pages F, Galon J: Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol. 2011, 29 (6): 610-618. 10.1200/JCO.2010.30.5425.

PubMedGoogle Scholar

Mahmoud SM, Paish EC, Powe DG, Macmillan RD, Grainge MJ, Lee AH, Ellis IO, Green AR: Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Oncol. 2011, 29 (15): 1949-1955. 10.1200/JCO.2010.30.5037.

PubMedGoogle Scholar

Rusakiewicz S, Semeraro M, Sarabi M, Desbois M, Locher C, Mendez R, Vimond N, Concha A, Garrido F, Isambert N, Chaigneau L, Le Brun-Ly V, Dubreuil P, Cremer I, Caignard A, Poirier-Colame V, Chaba K, Flament C, Halama N, Jäger D, Eggermont A, Bonvalot S, Commo F, Terrier P, Opolon P, Emile JF, Coindre JM, Kroemer G, Chaput N, Le Cesne A: Immune infiltrates are prognostic factors in localized gastrointestinal stromal tumors. Cancer Res. 2013, 73 (12): 3499-3510. 10.1158/0008-5472.CAN-13-0371.

PubMedGoogle Scholar

Rosenberg SA, Dudley ME: Adoptive cell therapy for the treatment of patients with metastatic melanoma. Curr Opin Immunol. 2009, 21 (2): 233-240. 10.1016/j.coi.2009.03.002.

PubMedCentralPubMedGoogle Scholar

Brown IE, Blank C, Kline J, Kacha AK, Gajewski TF: Homeostatic proliferation as an isolated variable reverses CD8+ T cell anergy and promotes tumor rejection. J Immunol. 2006, 177 (7): 4521-4529. 10.4049/jimmunol.177.7.4521.

PubMedGoogle Scholar

Watkins SK, Zhu Z, Riboldi E, Shafer-Weaver KA, Stagliano KE, Sklavos MM, Ambs S, Yagita H, Hurwitz AA: FOXO3 programs tumor-associated DCs to become tolerogenic in human and murine prostate cancer. J Clin Invest. 2011, 121 (4): 1361-1372. 10.1172/JCI44325.

PubMedCentralPubMedGoogle Scholar

Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbé C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ: Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010, 363 (8): 711-723. 10.1056/NEJMoa1003466.

PubMedCentralPubMedGoogle Scholar

Wolchok JD, Hodi FS, Weber JS, Allison JP, Urba WJ, Robert C, O'Day SJ, Hoos A, Humphrey R, Berman DM, Lonberg N, Korman AJ: Development of ipilimumab: a novel immunotherapeutic approach for the treatment of advanced melanoma. Annals of the New York Academy of Sciences. 2013, 1291: 1-13. 10.1111/nyas.12180.

PubMedCentralPubMedGoogle Scholar

Burnette BC, Liang H, Lee Y, Chlewicki L, Khodarev NN, Weichselbaum RR, Fu YX, Auh SL: The efficacy of radiotherapy relies upon induction of type i interferon-dependent innate and adaptive immunity. Cancer Res. 2011, 71 (7): 2488-2496. 10.1158/0008-5472.CAN-10-2820.

PubMedCentralPubMedGoogle Scholar

Balachandran VP, Cavnar MJ, Zeng S, Bamboat ZM, Ocuin LM, Obaid H, Sorenson EC, Popow R, Ariyan C, Rossi F, Besmer P, Guo T, Antonescu CR, Taguchi T, Yuan J, Wolchok JD, Allison JP, DeMatteo RP: Imatinib potentiates antitumor T cell responses in gastrointestinal stromal tumor through the inhibition of Ido. Nat Med. 2011, 17 (9): 1094-1100. 10.1038/nm.2438.

PubMedCentralPubMedGoogle Scholar

Frederick DT, Piris A, Cogdill AP, Cooper ZA, Lezcano C, Ferrone CR, Mitra D, Boni A, Newton LP, Liu C, Peng W, Sullivan RJ, Lawrence DP, Hodi FS, Overwijk WW, Lizée G, Murphy GF, Hwu P, Flaherty KT, Fisher DE, Wargo JA: BRAF inhibition is associated with enhanced melanoma antigen expression and a more favorable tumor microenvironment in patients with metastatic melanoma. Clin Cancer Res. 2013, 19 (5): 1225-1231. 10.1158/1078-0432.CCR-12-1630.

PubMedCentralPubMedGoogle Scholar

Liang H, Deng L, Chmura S, Burnette B, Liadis N, Darga T, Beckett MA, Lingen MW, Witt M, Weichselbaum RR, Fu Y: Radiation-induced equilibrium is a balance between tumor cell proliferation and T cell-mediated killing. J Immunol. 2013, 190 (11): 5874-5881. 10.4049/jimmunol.1202612.

PubMedCentralPubMedGoogle Scholar

Zeng J, See AP, Phallen J, Jackson CM, Belcaid Z, Ruzevick J, Durham N, Meyer C, Harris TJ, Albesiano E, Pradilla G, Ford E, Wong J, Hammers HJ, Mathios D, Tyler B, Brem H, Tran PT, Pardoll D, Drake CG, Lim M: Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas. Int J Radiat Oncol Biol Phys. 2013, 86 (2): 343-349. 10.1016/j.ijrobp.2012.12.025.

PubMedCentralPubMedGoogle Scholar

Reardon DA, Wucherpfennig KW, Freeman G, Wu CJ, Chiocca EA, Wen PY, Curry WT, Mitchell DA, Fecci PE, Sampson JH, Dranoff G: An update on vaccine therapy and other immunotherapeutic approaches for glioblastoma. Expert Rev Vaccines. 2013, 12 (6): 597-615. 10.1586/erv.13.41.

PubMedCentralPubMedGoogle Scholar

Hinrichs CS, Stevanovic S, Draper L, Somerville R, Wunderlich J, Restifo NP, Sherry R, Giao PQ, Kammula US, Yang JC, Rosenberg SA: HPV-targeted tumor-infiltrating lymphocytes for cervical cancer. J Clin Oncol. 2014, 32 (suppl; abstr LBA3008):

Google Scholar

Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF: Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010, 363 (5): 411-422. 10.1056/NEJMoa1001294.

PubMedGoogle Scholar

Varela-Rohena A, Carpenito C, Perez EE, Richardson M, Parry RV, Milone M, Scholler J, Hao X, Mexas A, Carroll RG, June CH, Riley JL: Genetic engineering of T cells for adoptive immunotherapy. Immunol Res. 2008, 42 (1–3): 166-181.

PubMedCentralPubMedGoogle Scholar

Johnson LA, Heemskerk B, Powell DJ, Cohen CJ, Morgan RA, Dudley ME, Robbins PF, Rosenberg SA: Gene transfer of tumor-reactive TCR confers both high avidity and tumor reactivity to nonreactive peripheral blood mononuclear cells and tumor-infiltrating lymphocytes. JImmunol. 2006, 177 (9): 6548-6559. 10.4049/jimmunol.177.9.6548.

Google Scholar

Wang X, Nishimura M: Genetically engineered (T cell receptor) T cells for adoptive therapy. Gene Therapy of Cancer. Edited by: Lattime EC, Gerson SL. 2013, San Diego (CA): Elsevier, 259-271. 3

Google Scholar

Choi Y, Yuen C, Maiti SN, Olivares S, Gibbons H, Huls H, Raphael R, Killian TC, Stark DJ, Lee DA, Torikai H, Monticello D, Kelly SS, Kebriaei P, Champlin RE, Biswal SL, Cooper LJ: A high throughput microelectroporation device to introduce a chimeric antigen receptor to redirect the specificity of human T cells. Biomed Microdevices. 2010, 12 (5): 855-863. 10.1007/s10544-010-9440-3.

PubMedGoogle Scholar

Singh H, Manuri PR, Olivares S, Dara N, Dawson MJ, Huls H, Hackett PB, Kohn DB, Shpall EJ, Champlin RE, Cooper LJ: Redirecting specificity of T-cell populations for CD19 using the sleeping beauty system. Cancer Res. 2008, 68 (8): 2961-2971. 10.1158/0008-5472.CAN-07-5600.

PubMedCentralPubMedGoogle Scholar

Hoyos V, Savoldo B, Quintarelli C, Mahendravada A, Zhang M, Vera J, Heslop HE, Rooney CM, Brenner MK, Dotti G: Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety. Leukemia. 2010, 24 (6): 1160-1170. 10.1038/leu.2010.75.

PubMedCentralPubMedGoogle Scholar

Xu Y, Zhang M, Ramos CA, Durett A, Liu E, Dakhova O, Liu H, Creighton CJ, Gee AP, Heslop HE, Rooney CM, Savoldo B, Dotti G: Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15. Blood. 2014, 123 (24): 3750-3759. 10.1182/blood-2014-01-552174.

PubMedCentralPubMedGoogle Scholar

Turtle CJ: Chimeric antigen receptor modified T cell therapy for B cell malignancies. Int J Hematol. 2014, 99 (2): 132-140. 10.1007/s12185-013-1490-x.

PubMedGoogle Scholar

Kochenderfer JN, Dudley ME, Feldman SA, Wilson WH, Spaner DE, Maric I, Stetler-Stevenson M, Phan GQ, Hughes MS, Sherry RM, Yang JC, Kammula US, Devillier L, Carpenter R, Nathan DA, Morgan RA, Laurencot C, Rosenberg SA: B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood. 2012, 119 (12): 2709-2720. 10.1182/blood-2011-10-384388.

PubMedCentralPubMedGoogle Scholar

Marcus A, Eshhar Z: Allogeneic chimeric antigen receptor-modified cells for adoptive cell therapy of cancer. Expert Opin Biol Ther. 2014, 14 (7): 947-954. 10.1517/14712598.2014.900540.

PubMedGoogle Scholar

Torikai H, Reik A, Liu PQ, Zhou Y, Zhang L, Maiti S, Huls H, Miller JC, Kebriaei P, Rabinovitch B, Lee DA, Champlin RE, Bonini C, Naldini L, Rebar EJ, Gregory PD, Holmes MC, Cooper LJ: A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR. Blood. 2012, 119 (24): 5697-5705. 10.1182/blood-2012-01-405365.

PubMedCentralPubMedGoogle Scholar

Boudreau JE, Bonehill A, Thielemans K, Wan Y: Engineering dendritic cells to enhance cancer immunotherapy. Mol Ther. 2011, 19 (5): 841-853. 10.1038/mt.2011.57.

PubMedCentralPubMedGoogle Scholar

Pinder-Schenck M, Antonia S: Genetically modified dendritic cell vaccines for solid tumors. Gene Therapy of Cancer. Edited by: Lattime EC, Gerson SL. 2013, San Diego (CA): Elsevier, 273-282. 3

Google Scholar

Jonuleit H, Giesecke-Tuettenberg A, Tuting T, Thurner-Schuler B, Stuge TB, Paragnik L, Kandemir A, Lee PP, Schuler G, Knop J, Enk AH: A comparison of two types of dendritic cell as adjuvants for the induction of melanoma-specific T-cell responses in humans following intranodal injection. Int J Cancer. 2001, 93 (2): 243-251. 10.1002/ijc.1323.

PubMedGoogle Scholar

Tsao H, Millman P, Linette GP, Hodi FS, Sober AJ, Goldberg MA, Haluska FG: Hypopigmentation associated with an adenovirus-mediated gp100/MART-1-transduced dendritic cell vaccine for metastatic melanoma. Arch Dermatol. 2002, 138 (6): 799-802.

PubMedGoogle Scholar

Marshall JL, Gulley JL, Arlen PM, Beetham PK, Tsang KY, Slack R, Hodge JW, Doren S, Grosenbach DW, Hwang J, Fox E, Odogwu L, Park S, Panicali D, Schlom J: Phase I study of sequential vaccinations with fowlpox-CEA(6D)-TRICOM alone and sequentially with vaccinia-CEA(6D)-TRICOM, with and without granulocyte-macrophage colony-stimulating factor, in patients with carcinoembryonic antigen-expressing carcinomas. J Clin Oncol. 2005, 23 (4): 720-731. 10.1200/JCO.2005.10.206.

PubMedGoogle Scholar

Wolff JA, Budker V: The mechanism of naked DNA uptake and expression. Adv Genet. 2005, 54: 3-20.

PubMedGoogle Scholar

Kutzler MA, Weiner DB: DNA vaccines: ready for prime time?. Nat Rev Genet. 2008, 9 (10): 776-788. 10.1038/nrg2432.

PubMedCentralPubMedGoogle Scholar

McNeel DG, Dunphy EJ, Davies JG, Frye TP, Johnson LE, Staab MJ, Horvath DL, Straus J, Alberti D, Marnocha R, Liu G, Eickhoff JC, Wilding G: Safety and immunological efficacy of a DNA vaccine encoding prostatic acid phosphatase in patients with stage D0 prostate cancer. J Clin Oncol. 2009, 27 (25): 4047-4054. 10.1200/JCO.2008.19.9968.

PubMedCentralPubMedGoogle Scholar

Norell H, Poschke I, Charo J, Wei WZ, Erskine C, Piechocki MP, Knutson KL, Bergh J, Lidbrink E, Kiessling R: Vaccination with a plasmid DNA encoding HER-2/neu together with low doses of GM-CSF and IL-2 in patients with metastatic breast carcinoma: a pilot clinical trial. J Transl Med. 2010, 8: 53-10.1186/1479-5876-8-53.

PubMedCentralPubMedGoogle Scholar

Staff C, Mozaffari F, Haller BK, Wahren B, Liljefors M: A Phase I safety study of plasmid DNA immunization targeting carcinoembryonic antigen in colorectal cancer patients. Vaccine. 2011, 29 (39): 6817-6822. 10.1016/j.vaccine.2010.12.063.

PubMedGoogle Scholar

Rosa DS, Ribeiro SP, Almeida RR, Mairena EC, Postol E, Kalil J, Cunha-Neto E: A DNA vaccine encoding multiple HIV CD4 epitopes elicits vigorous polyfunctional, long-lived CD4+ and CD8+ T cell responses. PLoS One. 2011, 6 (2): e16921-10.1371/journal.pone.0016921.

PubMedCentralPubMedGoogle Scholar

Garcia F, Petry KU, Muderspach L, Gold MA, Braly P, Crum CP, Magill M, Silverman M, Urban RG, Hedley ML, Beach KJ: ZYC101a for treatment of high-grade cervical intraepithelial neoplasia: a randomized controlled trial. Obstet Gynecol. 2004, 103 (2): 317-326. 10.1097/01.AOG.0000110246.93627.17.

PubMedGoogle Scholar

Auci D, Cecil D, Herendeen D, Broussard E, Liao J, Holt G, Disis M: Clinical application of plasmid-based cancer vaccines. Gene Therapy of Cancer. Edited by: Lattime EC, Gerson SL. 2013, San Diego (CA): Elsevier, 335-343. 3

Google Scholar

Karjoo Z, Ganapathy V, Hatefi A: Gene-directed enzyme prodrug cancer therapy. Gene Therapy of Cancer. Edited by: Lattime EC, Gerson SL. 2013, San Diego (CA): Elsevier, 77-91. 3

Google Scholar

Nicholas TW, Read SB, Burrows FJ, Kruse CA: Suicide gene therapy with Herpes simplex virus thymidine kinase and ganciclovir is enhanced with connexins to improve gap junctions and bystander effects. Histol Histopathol. 2003, 18 (2): 495-507.

PubMedGoogle Scholar

Agard C, Ligeza C, Dupas B, Izembart A, El Kouri C, Moullier P, Ferry N: Immune-dependent distant bystander effect after adenovirus-mediated suicide gene transfer in a rat model of liver colorectal metastasis. Cancer Gene Ther. 2001, 8 (2): 128-136. 10.1038/sj.cgt.7700281.

PubMedGoogle Scholar

Edelstein ML, Abedi MR, Wixon J, Edelstein RM: Gene therapy clinical trials worldwide 1989-2004-an overview. J Gene Med. 2004, 6 (6): 597-602. 10.1002/jgm.619.

PubMedGoogle Scholar

Alauddin MM, Shahinian A, Gordon EM, Bading JR, Conti PS: Preclinical evaluation of the penciclovir analog 9-(4-[(18)F]fluoro-3-hydroxymethylbutyl)guanine for in vivo measurement of suicide gene expression with PET. J Nucl Med. 2001, 42 (11): 1682-1690.

PubMedGoogle Scholar

Lin Y, Gerson S: Clinical trials using LB-P140K-MGMT for gliomas. Gene Therapy of Cancer. Edited by: Lattime EC, Gerson SL. 2013, San Diego (CA): Elsevier, 379-391. 3

Google Scholar

Maier P, Herskind C, Fleckenstein K, Spier I, Laufs S, Zeller WJ, Fruehauf S, Wenz F: MDR1 gene transfer using a lentiviral SIN vector confers radioprotection to human CD34+ hematopoietic progenitor cells. Radiat Res. 2008, 169 (3): 301-310. 10.1667/RR1067.1.

PubMedGoogle Scholar

Maier P, Spier I, Laufs S, Veldwijk MR, Fruehauf S, Wenz F, Zeller WJ: Chemoprotection of human hematopoietic stem cells by simultaneous lentiviral overexpression of multidrug resistance 1 and O(6)-methylguanine-DNA methyltransferase(P140K). Gene Ther. 2010, 17 (3): 389-399. 10.1038/gt.2009.133.

PubMedGoogle Scholar

Arai T, Miyoshi Y, Kim SJ, Akazawa K, Maruyama N, Taguchi T, Tamaki Y, Noguchi S: Association of GSTP1 expression with resistance to docetaxel and paclitaxel in human breast cancers. Eur J Surg Oncol. 2008, 34 (7): 734-738. 10.1016/j.ejso.2007.07.008.

PubMedGoogle Scholar

Oguri T, Fujiwara Y, Katoh O, Daga H, Ishikawa N, Fujitaka K, Yamasaki M, Yokozaki M, Isobe T, Ishioka S, Yamakido M: Glutathione S-transferase-pi gene expression and platinum drug exposure in human lung cancer. Cancer Lett. 2000, 156 (1): 93-99. 10.1016/S0304-3835(00)00447-X.

PubMedGoogle Scholar

Matranga C, Tomari Y, Shin C, Bartel DP, Zamore PD: Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell. 2005, 123 (4): 607-620. 10.1016/j.cell.2005.08.044.

PubMedGoogle Scholar

Seiradake E, Henaff D, Wodrich H, Billet O, Perreau M, Hippert C, Mennechet F, Schoehn G, Lortat-Jacob H, Dreja H, Ibanes S, Kalatzis V, Wang JP, Finberg RW, Cusack S, Kremer EJ: The cell adhesion molecule "CAR" and sialic acid on human erythrocytes influence adenovirus in vivo biodistribution. PLoS Pathog. 2009, 5 (1): e1000277-10.1371/journal.ppat.1000277.

PubMedCentralPubMedGoogle Scholar

Howe SJ, Mansour MR, Schwarzwaelder K, Bartholomae C, Hubank M, Kempski H, Brugman MH, Pike-Overzet K, Chatters SJ, de Ridder D, Gilmour KC, Adams S, Thornhill SI, Parsley KL, Staal FJ, Gale RE, Linch DC, Bayford J, Brown L, Quaye M, Kinnon C, Ancliff P, Webb DK, Schmidt M, von Kalle C, Gaspar HB, Thrasher AJ: Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. J Clin Invest. 2008, 118 (9): 3143-3150. 10.1172/JCI35798.

PubMedCentralPubMedGoogle Scholar

Schmidt M, Zickler P, Hoffmann G, Haas S, Wissler M, Muessig A, Tisdale JF, Kuramoto K, Andrews RG, Wu T, Kiem HP, Dunbar CE, von Kalle C: Polyclonal long-term repopulating stem cell clones in a primate model. Blood. 2002, 100 (8): 2737-2743. 10.1182/blood-2002-02-0407.

PubMedGoogle Scholar

Bartholomae CC, Glimm H, Von Kalle C, Schmidt M: Insertion site pattern: global approach by linear amplification-mediated PCR and mass sequencing. Methods Mol Biol. 2012, 859: 255-265. 10.1007/978-1-61779-603-6_15.

PubMedGoogle Scholar

Gillet NA, Malani N, Melamed A, Gormley N, Carter R, Bentley D, Berry C, Bushman FD, Taylor GP, Bangham CR: The host genomic environment of the provirus determines the abundance of HTLV-1-infected T-cell clones. Blood. 2011, 117 (11): 3113-3122. 10.1182/blood-2010-10-312926.

PubMedCentralPubMedGoogle Scholar

Novartis: Investigational New Drug Development Program. 2014, [http://www.novartisoncology.com/ct/pipelineHome]

Google Scholar

Published
2019-01-30
Section
Review