Cancer Vaccines

1. Cancer Vaccines • Medicines that belong to a class of substances known as biological response modifiers. • Biological response modifiers stimulate or restore the immune system’s ability to fight against infectious diseases. • Cancer vaccines are designed to boost the body’s natural ability to protect itself, through the immune system, from dangers posed by damaged or abnormal cells such as cancer cells. • These vaccines have become a therapeutic possibility due to recognition of tumor antigens by the host’s immune system.

2. Types of cancer vaccines • There are 2 broad categories of cancer vaccines : • Preventive/ Prophylactic vaccines: to prevent cancer from developing in healthy people • Treatment/ Therapeutic vaccines: to treat an existing cancer by strengthening the body’s natural defenses against the cancer

3. Cancer Antigens • They are classified in 4 groups: • Unique antigens- series of neo-antigens that result from mutations that arise from the inherent genomic instability of tumors • Cancer –testis antigens- normally expressed in male germ cells and are silenced in healthy somatic cells, but are re-expressed in certain cancers • Differentiation antigens- present in both tumor cells and their normal cellular counterpart • Over-expressed antigens- present in healthy tissue, but are extensively represented in cancerous cells.

4. Challenges facing vaccines • Choosing the right antigen • Choosing the right adjuvant • Generating the right type of immune response • Elicitation of long-term memory • Aging immune system • Tumour-induced immunosuppression and immune evasion

5. Preventive/Prophylactic cancer vaccines • Administered before the occurrence of tumors to individuals who are at a high risk of developing tumors or have been diagnosed with premalignant changes in target tissues. • Vaccine based on antigen that is expressed by the tumor is administered in an immunostimulatory preparation (adjuvant) that can activate Langerhan cell (DCs) • Activated LCs take up the antigen, traffic draining lymph nodes and present antigen to t-cells • B-cells are also activated- expected outcome is generation of tumor specific antibodies and clonal expansion of tumor-specific T-cells • Clonal expansion is followed by generation of memory cells specific for the tumor antigens

6. If a tumor begins to grow, tumor antigens that reach the draining lymph nodes reactivate tumor specific memory cells and elicit a swift secondary immune response • Response is characterized by large number of effector t-cells, high titer of antibodies and continuous activation of the DCs

7. Incipient tumor has not been allowed to grow large and heterogenous • Easily eliminated by the prepared immune response • Memory compartment is further expanded by this tumour-mediated boost.

8. Therapeutic vaccines • Therapeutic vaccines are administered after the tumour is diagnosed at the time of interaction between tumour and the immune system

9. FDA approved vaccines • FDA approved preventive vaccines - vaccines against the hepatitis B virus, which can cause liver cancer, and vaccines against human papillomavirus types 16 and 18, which are responsible for about 70 percent of cervical cancer cases. • FDA approved treatment vaccines- for certain men with metastatic prostate cancer. • Researchers are developing treatment vaccines against many types of cancer and testing them in clinical trials.

10. Additional Research • Researchers have identified many cancer-associated antigens, these molecules vary widely in their capacity to stimulate a strong anticancer immune response. Two major areas of research aimed at developing better cancer treatment vaccines involve the identification of novel cancer-associated antigens that may prove more effective in stimulating immune responses than the already known antigens and the development of methods to enhance the ability of cancer-associated antigens to stimulate the immune system. Research is also under way to determine how to combine multiple antigens within a single cancer treatment vaccine to produce optimal anticancer immune responses • The most promising avenue of cancer vaccine research is aimed at better understanding the basic biology underlying how immune system cells and cancer cells interact. New technologies are being created as part of this effort. For example, a new type of imaging technology allows researchers to observe killer T cells and cancer cells interacting inside the body • Researchers are also trying to identify the mechanisms by which cancer cells evade or suppress anticancer immune responses. A better understanding of how cancer cells manipulate the immune system could lead to the development of new drugs that block those processes and thereby improve the effectiveness of cancer treatment vaccines . • For example, some cancer cells produce chemical signals that attract white blood cells known as regulatory T cells, or Tregs, to a tumor site. Tregs often release cytokines that suppress the activity of nearby killer T cells. The combination of a cancer treatment vaccine with a drug that would block the negative effects of one or more of these suppressive cytokines on killer T cells might improve the vaccine’s effectiveness in generating potent killer T cell antitumor responses.