Lollini PL, Cavallo F, Nanni P, Forni G. Vaccines for tumour prevention. Nature Reviews Cancer2006; 6(3):204–216.
Cancer vaccines Muhammad Uzair Shah Hashmi Ug-3, ASAB NUST, H-12 Submitted To : Dr. Sadia Rashid
Cancer vaccinesCancer vaccines are medicines that belong to a class of substances known as biological responsemodifiers. Biological response modifiers work by stimulating or restoring the immune system’sability to fight infections and disease. Two broad types of cancer vaccines•Preventive (or prophylactic) vaccines prevent cancer from developing in healthy people.•Treatment (or therapeutic) vaccines treat an existing cancer by strengthening the body’s natural defenses against the cancer. Lollini PL, Cavallo F, Nanni P, Forni G. Vaccines for tumour prevention. Nature Reviews Cancer2006; 6(3):204–216.
Antitumor response of prophylactic vaccine• Given to people who have very high risk of developing cancers that have been diagnosed with premalignant changes in tissues• Vaccine based antigen along with immunomodulatory is introduced that activate the Langerhans cells.• T cells are activated when the tumor antigen is presented to them along with B cells that produce tumor specific antibodies• Clonal expansion is the next process that occurs along with the memory cell formation.• In future if tumor start its growth tumor specific memoray cells wil be reactivated by the tumor antigen reaching lymph nodes• Secondary immune response1. Large no of effector T cells2. High titer of antibodies3. Continues activation of DC at the site• Tumor will not be allowed to grow large and is easiy eliminated as a result of secondary immune response. http://fog.its.uiowa.edu/~immuno/classMaterial/Advanced%20Topics%202004/Sept29Session%2011/Olivera.pdf
Anti tumor response of therapeutic vaccine• Administered after tumor diagnosis when tumor is interacting with immune system.• Vaccine (autologous/defined tumor antigen + immunomodulators) to activate Langerhan’s cells.• Taken up by activated Langerhans cells and presented to T cells• B-cell activated, clonal expansion, production of tumor specific antibodies.• Migration of tumor sensitive T cells at site of tumor metastasis.(attempt to kill tumor cells expressing vaccine Ag.)• Immunosuppressive tumor microenvironment suppresses their function.• Establishment of tumor heterogeneity. Leading to lost of tumor antigen expression or resistance immune effectors mechanism evading immune evasion.• Tumor cells with antigen not recognized by T-cells and Ab. They are resistant to immune destruction. http://fog.its.uiowa.edu/~immuno/classMaterial/Advanced%20Topics%202004/Sept29Session%2011/Olivera.pdf
Cancer vaccine types• Tumor cell vaccines Utilizes whole tumor cells rendered safe by irradiation. -Autologous vs. Allogenic• Dendritic cell vaccinesDendritic cells can be generated outside of the body. Cancers these vaccines are being studied in: prostate, melanoma, breast, lung, colorectal, kidney, leukemia, and non-Hodgkin lymphoma• Antigen vaccinesThis includes peptide vaccines: only one specific epitope is injected.Cancers these vaccines are being studied in include: kidney cancer, pancreatic cancer, melanoma, ovarian cancer, breast cancer, prostate cancer, and colorectal cancer. http://oncolink.org/treatment/article.cfm?c=11&s=80&id=252
Types contd…• 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.• 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. http://oncolink.org/treatment/article.cfm?c=11&s=80&id=252
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!!