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Cancer Vaccines: A novel approach to cancer Cancer Statistics • Cancer still remains a major cause of death worldwide despite many therapies and treatment modalities available. • ACS predicted in 2006: 565,000 Americans would die of cancer and approximately 1.4 million would be diagnosed. Immunotherapy: New class of cancer treatment • Considered by many to be the “fourth modality of cancer treatment” after chemotherapy, radiation, and surgery. • Based on utilizing the patient’s immune system to fight the cancer. • Cancer vaccines fall under this category of treatment. Cancer Vaccines • Majority used for treatment not prevention. • May offer method that can enhance the immune response against cancer. • Cancer Vaccines: Different than HPV vaccine and traditional prophylactic vaccines. • HPV Vaccine: Immunity to the virus, which causes cervical cancer. • Traditional prophylactic vaccines: As with the HPV vaccine, provide immunity to a particular disease. • At this time, cancer vaccines are only available in clinical trials. Science behind Cancer Vaccines Key players • Dendritic Cell: ~Remarkable ability to capture and process antigen. ~ Antigen presenting cell-presents antigen to T-cell to mount an immune response. • T-Cell: ~ Mediates immune response. 5 Main Types of Cancer Vaccines • Tumor cell vaccines -Autologous vs. Allogenic • Dendritic cell vaccines • Antigen vaccines • Anti-Idiotype vaccines • DNA vaccines Tumor Cell Vaccines • Utilizes whole tumor cells rendered safe by irradiation. • Specific immune response initiated when injected into body. • Body attacks similar cells that remain in body. • Autologous-removed tumor cells from patient’s own body. • Allogenic-removed tumor cells from someone other than the patient. • Many different epitopes are recognized. • Cancers these vaccines are being studied in: melanoma, colorectal, kidney, ovarian, breast, lung, and leukemia. Dendritic Cell Vaccines • Dendritic cells can be generated outside of the body. • Dendritic cells are made capable of recognizing antigen by gene therapy and exposure to antigen. • Dendritic cells injected into the individual stimulating an immune response. • Cancers these vaccines are being studied in: prostate, melanoma, breast, lung, colorectal, kidney, leukemia, and non-Hodgkin lymphoma. Antigen Vaccines • This includes peptide vaccines: only one specific epitope is injected. • Vast amounts of antigen can be created in laboratories. • Some antigens are specific for a certain type of cancer; others may induce an immune response in several cancers. • Cancers these vaccines are being studied in include: kidney cancer, pancreatic cancer, melanoma, ovarian cancer, breast cancer, prostate cancer, and colorectal cancer. Anti-Idiotype Vaccines • Based on the idea that antibodies can also act as antigens triggering an immune response. • This idea would be used to create a vaccine in which the antibodies (which resemble the cancer cells) would be injected into the cancer patient eliciting an immune response. • Primary target is lymphoma. DNA vaccines • Introduction of tumor genes instead of tumor antigen itself. • Cells in the body take up the injected DNA. Specific antigens would then be made on a continuous basis. • The idea of these vaccines is that the body would be provided with a constant supply of antigens to allow the immune response to continue against the cancer. • Cancers these vaccines are being studied in: prostate cancer, leukemia, melanoma, and head and neck cancer. OncoVAX by Intracel • • • • Autologous vaccine for Stage II colon cancer. Received fast-track status from FDA in 2006. Used in an adjuvant setting. Study: 254 patients received either OncoVAX or placebo. • Improves 5-year survival and recurrence-free interval. • 57.1% relative risk reduction. Sipuleucel-T (Provenge) by Dendreon • Dendritic cell vaccine for treatment of asymptomatic Androgen-Independent Prostate Cancer (AIPC). • Received fast-track status by FDA in 2005. • Target-prostatic acid phosphatase (PAP), which is found in 95% of prostate cancers. • Study of Provenge vs. Placebo. ~98 men with AIPC. ~3.3 month or 21% improvement in median survival. ~3-year follow-up: 32% of men that received Provenge alive compared to 21% placebo. ~52% increase in survival rate. Lung Cancer Vaccine at UK • • • • Dendritic cell vaccine. Treatment of non-small cell lung cancer (NSCLC). Study: Patients with Stage IA to IIIB were given vaccine. Patients treated prior with surgery, chemoradiation, or multimodality therapy. • Results published for 16 patients. ~5/16: no clear immunologic response. ~5/16: antigen-independent response. ~6/16: response may have been tumor specific. ~response shown in various stages of NSCLC. Conclusion • Clear that the immune system displays a highly developed response against cancer. • May be more effective in cancers that are not advanced. • Majority will probably be used as adjuvants. • Clinically not yet at our fingertips. • Much progress has been made in this area of research. • More research still needs to be done including larger studies. • Researchers are actively trying to overcome hurdles in the making of these vaccines. • Could make a big impact on our approach to cancer. • Most importantly these vaccines could mean better quality of life and longer survival for our patients!! References • • • • • • • • • • • • • • • • Armstrong ACª, Eaton D, Ewing JC. Cellular immunity for cancer. British Medical Journal. 2001;323:1289-1293. PMID 11731394. Armstrong ACb, Hawkins RE. Vaccines in oncology: background and clinical potential. The British Journal of Radiology. 2001;74: 991-1002. PMID 11709463. Berzofsky JA, Terabe M, Oh S, Belyakov IM, Ahlers JD, Janik JE, et al. Progess on new vaccine strategies for the immunotherapy and prevention of cancer. J. Clin. Interest. 2004; 113:1515-1525. PMID 15173875. Blattman JN., Greenberg PD. Cancer immunotherapy: A treatment for the masses. Science. 2004;305:200-205. PMID 15247469. Brand TC, Tolcher AW. Management of high risk metastatic prostate cancer: the case for novel therapies. The Journal of Urology. 2006;176: S76-S80. PMID 17084174. Cancer.org. [homepage on the Internet]. Atlanta: American Cancer Society, Inc.; c2006. [revised 2005 April 11]. Available from http://www.cancer.org/ Dendreon.com [homepage on the Internet]. Seattle: Dendreon Corporation c2006. Available from http://www.dendreon.com/ Department of Microbiology, Immunology, and Molecular Genetics Faculty Listing. Yannelli JR. University of Kentucky Chandler Medical Center c2004. Available from http://www.mc.uky.edu/microbiology/yannelli.asp Goldsby RA, Kindt TJ, Osborne BA, Kuby Janis. Immunology. Fifth Ed. New York: W.H. Freeman and Company; 2003. Groot CA, Vermorken JB, Hanna Jr MG, Verboom P, Groot MT, GJ Bonsel, et al. Immunotherapy with autologous tumor cell-BCG vaccine in patients with colon cancer: a prospective study of medical and economic benefits. ScienceDirect. 2005;23: 2379-2387. Hirschowitz EA, Foody T, Krysico R, Dickson L, Sturgill J, Yannelli J. Autolougous dendritic cell vaccines for nonsmall-cell lung cancer. Journal of Clinical Oncology. 2004;22: 2808-2815. Intracel.com. [homepage on the Internet] Frederick: Intracel Corporation c2006. Available from http://www.intracel.com/ Tabi Z a, Mann S. Challenges for cancer vaccine development. Science Direct. Advanced Drug Delivery Reviews. In press 2006. Tabi Zb, Mann S. Human Cancer vaccines. Science Direct. Advanced Drug Delivery Reviews. In press 2006. Tarassoff CP, Arlen PM, Gulley JL. Therapeutic vaccines for prostate cancer. The Oncologist. 2006;11:451-462. PMID 16720845.