Abstract
Current treatment modalities of surgical resection and chemotherapy against cancers have improved survival. However, mortality from tumor recurrence remains high. Immunotherapy and gene therapy are potential additions to the treatment arsenal in the care of cancer patients. These novel therapeutic approaches need further investigation in in vitro and in vivo models as they are developed for potential use in humans. Here we reviewed immunotherapies and gene therapies that included clinical trials against cancers (mainly focusing on pancreatic cancer) suggesting the strong possibility of using these novel approaches.
Similar content being viewed by others
References
Wingo PA, Tong T, Bolden S. Cancer statistics, 1995. CA Cancer J Clin 1995;45:8–30.
Brennan MF. Surgical therapy and prognosis of soft tissue sarcoma (in German). Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen 1993;64:449–454.
Geer RJ, Brennan MF. Prognostic indicators for survival after resection of pancreatic adenocarcinoma. Am J Surg 1993;165:68–72; discussion 72–3.
Conlon KC, Klimstra DS, Brennan MF. Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann Surg 1996;223:273–279.
Yeo CJ, Cameron JL. Improving results of pancreaticoduodenectomy for pancreatic cancer. World J Surg 1999;23:907–912.
Yeo CJ, Abrams RA, Grochow LB, Sohn TA, Ord SE, Hruban RH, et al. Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience. Ann Surg 1997;225:621–633; discussion 633–6.
Kalser MH, Ellenberg SS. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 1985;120:899–903.
Gastrointestinal Tumor Study Group. Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Cancer 1987;59:2006–2010.
Saito I. Gene therapy vector: adenovirus vector (in Japanese). Tanpakushitsu Kakusan Koso 1997;42:1798–1805.
Brody SL, Crystal RG. Adenovirus-mediated in vivo gene transfer. Ann NY Acad Sci 1994;716:90–101; discussion 101–3.
Crystal RG. In vivo and ex vivo gene therapy strategies to treat tumors using adenovirus gene transfer vectors. Cancer Chemother Pharmacol 1999;43:suppl:S90–S99.
Wu Q, Moyana T, Xiang J. Cancer gene therapy by adenovirus-mediated gene transfer. Curr Gene Ther 2001;1:101–122.
Varda-Bloom N, Shaish A, Gonen A, Levanon K, Greenbereger S, Ferber S, et al. Tissue-specific gene therapy directed to tumor angiogenesis. Gene Ther 2001;8:819–827.
Freeman SM, Whartenby KA, Freeman JL, Abboud CN, Marrogi AJ. In situ use of suicide genes for cancer therapy. Semin Oncol 1996;23:31–45.
Hassan W, Sanford MA, Woo SL, Chen SH, Hall SJ. Prospects for herpes-simplex-virus thymidine-kinase and cytokine gene transduction as immunomodulatory gene therapy for prostate cancer. World J Urol 2000;18:130–135.
Nasu Y, Kusaka N, Saika T, Tsushima T, Kumon H. Suicide gene therapy for urogenital cancer: current outcome and prospects. Mol Urol 2000;4:67–71.
van Dillen IJ, Mulder NH, Vaalburg W, de Vries EF, Hospers GA. Influence of the bystander effect on HSV-tk/GCV gene therapy. A review. Curr Gene Ther 2002;2:307–322.
Bi WL, Parysek LM, Warnick R, Stambrook PJ. In vitro evidence that metabolic cooperation is responsible for the bystander effect observed with HSV tk retroviral gene therapy. Hum Gene Ther 1993;4:725–731.
Freeman SM, Abboud CN, Whartenby KA, Packman CH, Koeplin DS, Moolten FL, et al. The “bystander effect”: tumor regression when a fraction of the tumor mass is genetically modified. Cancer Res 1993;53:5274–5283.
Schwarzenberger P, Harrison L, Weinacker A, Gaumer R, Theodossiou C, Summer W, et al. Gene therapy for malignant mesothelioma: a novel approach for an incurable cancer with increased incidence in Louisiana. J LA State Med Soc 1998;150:168–174.
Rosenfeld ME, Vickers SM, Raben D, Wang M, Sampson L, Feng M, et al. Pancreatic carcinoma cell killing via adenoviral mediated delivery of the herpes simplex virus thymidine kinase gene. Ann Surg 1997;225:609–618; discussion 618–20.
Aoki K, Yoshida T, Matsumoto N, Ide H, Hosokawa K, Sugimura T, et al. Gene therapy for peritoneal dissemination of pancreatic cancer by liposome-mediated transfer of herpes simplex virus thymidine kinase gene. Hum Gene Ther 1997;8:1105–1113.
Oldfield EH, Ram Z, Culver KW, Blaese RM, DeVroom HL, Anderson WF, et al. Gene therapy for the treatment of brain tumors using intra-tumoral transduction with the thymidine kinase gene and intravenous ganciclovir. Hum Gene Ther 1993;4:39–69.
Hwang HC, Smythe WR, Elshami AA, Kucharczuk JC, Amin KM, Williams JP, et al. Gene therapy using adenovirus carrying the herpes simplex-thymidine kinase gene to treat in vivo models of human malignant mesothelioma and lung cancer. American J Respir Cell Mol Biol 1995;13:7–16.
Nakada Y, Saito S, Ohzawa K, Morioka CY, Kita K, Minemura M, et al. Antisense oligonucleotides specific to mutated K-ras genes inhibit invasiveness of human pancreatic cancer cell lines. Pancreatology 2001;1:314–319.
Wickstrom E. Oligonucleotide treatment of ras-induced tumors in nude mice. Mol Biotechnol 2001;18:35–55.
Tsuchida T, Kijima H, Hori S, Oshika Y, Tokunaga T, Kawai K, et al. Adenovirus-mediated anti-K-ras ribozyme induces apoptosis and growth suppression of human pancreatic carcinoma. Cancer Gene Ther 2000;7:373–383.
Barton CM, Staddon SL, Hughes CM, Hall PA, O’sullivan C, Klöppel G, et al. Abnormalities of the p53 tumour suppressor gene in human pancreatic cancer. Br J Cancer 1991;64:1076–1082.
Bischoff JR, Kirn DH, Williams A, Heise C, Horn S, Muna M, et al. An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science 1996;274:373–376.
Heise C, Sampson-Johannes A, Williamu A, McCormick F, Von Hoff DD, Kirn DH. ONYX-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and antitumoral efficacy that can be augmented by standard chemotherapeutic agents. Nat Med 1997;3:639–645.
Mulvihill S, Warren R, Venook A, Adler A, Randlev B, Heise C, et al. Safety and feasibility of injection with an E1B-55 kDa gene-deleted, replication-selective adenovirus (ONYX-015) into primary carcinomas of the pancreas: a phase I trial. Gene Ther 2001;8:308–315.
Cohen EE, Rudin CM. ONYX-015. Onyx Pharmaceuticals. Curr Opin Invest Drugs 2001;2:1770–1775.
Greten TF, Jaffee EM. Cancer vaccines. J Clin Oncol 1999;17:1047–1060.
Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, Brose K, et al. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA 1993;90:3539–3543.
Toes RE, Bloom RJ, van der Voort E, Offringa R, Melief CJ, Kast WM. Protective antitumor immunity induced by immunization with completely allogeneic tumor cells. Cancer Res 1996;56:3782–3787.
Thomas MC, Greten TF, Pardoll DM, Jaffee EM. Enhanced tumor protection by granulocyte-macrophage colony-stimulating factor expression at the site of an allogeneic vaccine. Hum Gene Ther 1998;9:835–843.
Simons JW. Bioactivity of human GM-CSF gene therapy in metastatic renal cell carcinoma and prostate cancer. Hinyokika Kiyo 1997;43:821–822.
Soiffer R, Lynch T, Mihm M, Jung K, Rhuda C, Schmallinger JC, et al. Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma. Proc Natl Acad Sci USA 1998;95:13141–13146.
Simons JW, Mikhak B, Chang JF, DeMarzo AM, Carducci MA, Lim M, et al. Induction of immunity to prostate cancer antigens: results of a clinical trial of vaccination with irradiated autologous prostate tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor using ex vivo gene transfer. Cancer Res 1999;59:5160–5168.
Jaffee EM, Schtte M, Gossett J, Morsberger LA, Adler AJ, Thomas M, et al. Development and characterization of a cytokine-secreting pancreatic adenocarcinoma vaccine from primary tumors for use in clinical trials. The cancer journal from Sci Am 1998;4:194–203.
Jaffee EM, Hruban RH, Biedrzycki B, Laheru D, Schepers K, Sauter PR, et al. Novel allogeneic granulocyte-macrophage colony-stimulating factor-secreting tumor vaccine for pancreatic cancer: a phase I trial of safety and immune activation. J Clin Oncol 2001;19:145–156.
Thomas AM, Santarsiero LM, Lutz ER, Armstrong TD, Chen YC, Huang LQ, et al. Mesothelin-specific CD8(+) T cell responses provide evidence of in vivo cross-priming by antigen-presenting cells in vaccinated pancreatic cancer patients. J Exp Med 2004;200:297–306.
Laheru D, Lutz E, Burke J, Biedrzycki B, Solt S, Onners B, et al. Allogeneic granulocyte macrophage colony-stimulating factor-secreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer: a pilot study of safety, feasibility, and immune activation. Clin Cancer Res 2008;14:1455–1463.
Egen JG, Kuhns MS, Allison JP. CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nat Immunol 2002;3:611–618.
Small EJ, Tchekmedyian NS, Rini BI, Fong L, Lowy I, Allison JP. A pilot trial of CTLA-4 blockade with human anti-CTLA-4 in patients with hormone-refractory prostate cancer. Clin Cancer Res 2007;13:1810–1815.
Langer LF, Clay TM, Morse MA. Update on anti-CTLA-4 antibodies in clinical trials. Expert Opin Biol Ther 2007;7:1245–1256.
Morse MA, Hobeika AC, Osada T, Serra D, Niedzwiecki D, Lyerly HK, et al. Depletion of human regulatory T cells specifically enhances antigen-specific immune responses to cancer vaccines. Blood 2008;112:610–618.
Kondo H, Hazama S, Kawaoka T, Yoshino S, Yoshida S, Tokuno K, et al. Adoptive immunotherapy for pancreatic cancer using MUC1 peptide-pulsed dendritic cells and activated T lymphocytes. Anticancer Res 2008;28:379–387.
Heemskerk B, Heemskerk B, Liu K, Dudley ME, Johnson LA, Kaiser A, et al. Adoptive cell therapy for patients with melanoma, using tumor-infiltrating lymphocytes genetically engineered to secrete interleukin-2. Hum Gene Ther 2008;19:496–510.
Adams S, O’Neill DW, Nonaka D, Hardin E, Chiriboga L, Siu K, et al. Immunization of malignant melanoma patients with full-length NY-ESO-1 protein using TLR7 agonist imiquimod as vaccine adjuvant. J Immunol 2008;181:776–784.
Bargou R, Leo E, Zugmaier G, Klinger M, Goebeler M, Knop S, et al. Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science 2008;321:974–977.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Yoshimura, K., Olino, K., Edil, B.H. et al. Immuno- and gene-therapeutic strategies targeted against cancer (mainly focusing on pancreatic cancer). Surg Today 40, 404–410 (2010). https://doi.org/10.1007/s00595-009-4120-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00595-009-4120-8