Gene Therapy of Cancer

  • Kewal K. Jain


Gene therapy is defined as the transfer of defined genetic material to specific target cells of a patient for the ultimate purpose of preventing or altering a particular disease state (Jain 1998). It has three components: (1) identification of the gene that is mutated in a disease and obtaining a healthy copy of that gene, (2) carrier or delivery vehicle called vectors to deliver the healthy gene to a patient’s cells, and (3) additional DNA elements that turn on the healthy gene in the right cells and at the right levels. Gene therapy usually involves in situ production of therapeutic proteins but some approaches require suppression of gene expression to achieve therapeutic effects. Applications of gene therapy would be narrow if confined only to transfer of defined genetic material to specific target cells using vectors, which are usually viral but several nonviral vectors are used as well. Genes and DNA can be introduced without the use of vectors, and various techniques are being used to modify the function of genes in vivo without gene transfer, e.g., gene repair. Gene medicines may modify the effects of genes. If one includes cell therapy, particularly with the use of genetically modified cells, the scope of gene therapy becomes much broader. As a further extension, one can include genetically modified bacteria for delivery of therapeutic agents. Gene therapy can now be combined with antisense techniques and RNA interference (RNAi), further increasing the therapeutic scope. Details of gene therapy techniques are described in detail in a special report on this topic (Jain 2013). Cancer, the most important application of gene therapy currently, is the topic of this chapter.


Gene Therapy Cancer Vaccine Epidermal Growth Factor Receptor Expression Chimeric Antigen Receptor Autologous Hematopoietic Stem Cell Transplantation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Adams C, McCarthy HO, Coulter JA, et al. Nitric oxide synthase gene therapy enhances the toxicity of cisplatin in cancer cells. J Gene Med 2009;11:160-8.CrossRefGoogle Scholar
  2. Breitbach CJ, Arulanandam R, De Silva N, et al. Oncolytic Vaccinia Virus Disrupts Tumor-Associated Vasculature in Humans. Cancer Res 2013;73;1265-75.CrossRefGoogle Scholar
  3. Brentjens RJ, Santos E, Nikhamin Y, et al. Genetically targeted T cells eradicate systemic acute lymphoblastic leukemia xenografts. Clin Cancer Res 2007;13:5426-35.CrossRefGoogle Scholar
  4. Cerullo V, Koski A, Vähä-Koskela M, Hemminki A. Oncolytic adenoviruses for cancer immunotherapy: data from mice, hamsters, and humans. Adv Cancer Res 2012;115:265-318.Google Scholar
  5. Ciceri F, Bonini C, Marktel S, et al. Antitumor effects of HSV-TK-engineered donor lymphocytes after allogeneic stem-cell transplantation. Blood 2007;109:4698-707.CrossRefGoogle Scholar
  6. Cole C, Qiao J, Kottke T, et al. Tumor-targeted, systemic delivery of therapeutic viral vectors using hitchhiking on antigen-specific T cells. Nat Med 2005;11:1073-81.CrossRefGoogle Scholar
  7. Das SK, Sarkar S, Dash R, et al. Cancer terminator viruses and approaches for enhancing therapeutic outcomes. Adv Cancer Res 2012;115:1-38.Google Scholar
  8. Dufes C, Keith WN, Bilsland A, et al. Synthetic Anticancer Gene Medicine Exploits Intrinsic Antitumor Activity of Cationic Vector to Cure Established Tumours. Cancer Res 2005;65:8079-84.CrossRefGoogle Scholar
  9. Fisher PB. Is mda-7/IL-24 a “Magic Bullet” for Cancer? Cancer Research 2005;65:10128-38.CrossRefGoogle Scholar
  10. Grosel A, Sersa G, Kranjc S, et al. Electrogene Therapy with p53 of Murine Sarcomas Alone or Combined with Electrochemotherapy Using Cisplatin. DNA and Cell Biology 2006;25:674-83.CrossRefGoogle Scholar
  11. Grossardt C, Engeland CE, Bossow S, et al. GM-CSF-armed oncolytic measles virus is an effective therapeutic cancer vaccine. Hum Gene Ther 2013;24:644-54.CrossRefGoogle Scholar
  12. Han Z, Wang H, Hallahan DE. Radiation-Guided Gene Therapy of Cancer. TCRT 2006;5:437-444.Google Scholar
  13. Heo J, Reid T, Ruo L, et al. Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer. Nat Med 2013;19:329-36.CrossRefGoogle Scholar
  14. Jain KK. Textbook of Gene Therapy. Hogrefe & Huber, Toronto-Seattle-Göttingen, 1998.Google Scholar
  15. Jain KK. Gene therapy: technologies, markets and companies. Jain PharmaBiotech Publications, Basel, 2013.Google Scholar
  16. Kuruppu D, Brownell AL, Zhu A, et al. Positron emission tomography of herpes simplex virus 1 oncolysis. Cancer Res 2007;67:3295-300.CrossRefGoogle Scholar
  17. Maier P, Veldwijk MR, Wenz F. Radioprotective gene therapy. Expert Opin Biol Ther 2011;11:1135-51.CrossRefGoogle Scholar
  18. Meng Lin M, Kim HH, et al. Iron oxide-based nanomagnets in nanomedicine: fabrication and applications. Nano Rev 2010;1. doi:  10.3402/nano.v1i0.4883.
  19. Plog MS, Guyre CA, Roberts BL, et al. Preclinical Safety and Biodistribution of Adenovirus-Based Cancer Vaccines After Intradermal Delivery. Hum Gene Ther 2006;17:705-16.CrossRefGoogle Scholar
  20. Rai R, Dai H, Multani AS, et al. BRIT1 regulates early DNA damage response, chromosomal integrity, and cancer. Cancer Cell 2006;10:1-13.CrossRefGoogle Scholar
  21. Ramos CA, Dotti G. Chimeric antigen receptor (CAR)-engineered lymphocytes for cancer therapy. Expert Opin Biol Ther 2011;11:855-73.CrossRefGoogle Scholar
  22. Samaranayake H, Määttä AM, Pikkarainen J, Ylä-Herttuala S. Future prospects and challenges of antiangiogenic cancer gene therapy. Hum Gene Ther 2010;21:381-96.CrossRefGoogle Scholar
  23. Samaranayake H, Wirth T, Schenkwein D, et al. Challenges in monoclonal antibody-based therapies. Ann Med 2009;41:322-31.CrossRefGoogle Scholar
  24. Sarkar D, Lebedeva IV, Su Z, et al. Eradication of Therapy-Resistant Human Prostate Tumors Using a Cancer Terminator Virus. Cancer Res 2007;67:5434-42.CrossRefGoogle Scholar
  25. Su N, Pan YX, Zhou M, et al. Correlation between asparaginase sensitivity and asparagine synthetase protein content, but not mRNA, in acute lymphoblastic leukemia cell lines. Pediatr Blood Cancer 2008;50:274-9.CrossRefGoogle Scholar
  26. Thorne SH, Negrin RS, Contag CH. Synergistic Antitumor Effects of Immune Cell-Viral Biotherapy. Science 2006;311:1780-4.CrossRefGoogle Scholar
  27. Toth K, Dhar D, Wold WS. Oncolytic (replication-competent) adenoviruses as anticancer agents. Expert Opin Biol Ther 2010;10:353-68.CrossRefGoogle Scholar
  28. van den Pol AN, Davis JN. Highly attenuated recombinant vesicular stomatitis virus VSV-12′GFP displays immunogenic and oncolytic activity. J Virol 2013;87:1019-34.CrossRefGoogle Scholar
  29. Waldner MJ, Neurath MF. Gene therapy using IL 12 family members in infection, auto immunity, and cancer. Curr Gene Ther 2009;9:239-47.CrossRefGoogle Scholar
  30. Wang Y, Liu S, Li CY, Yuan F. A Novel Method for Viral Gene Delivery in Solid Tumors. Cancer Research 2005;65:7541-5.Google Scholar
  31. Ye S, Yang W, Wang Y, et al. Cationic liposome-mediated nitric oxide synthase gene therapy enhances the antitumor effects of cisplatin in lung cancer. Int J Mol Med 2013;31:33-42.Google Scholar
  32. Zhou G, Roizman B. Construction and properties of a herpes simplex virus 1 designed to enter cells solely via the IL-13α2 receptor. PNAS 2006;103:5508-13.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Kewal K. Jain
    • 1
  1. 1.Jain PharmaBiotechBaselSwitzerland

Personalised recommendations