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CANCER VACCINES

CANCER VACCINES. What are cancer vaccines?. Cancer vaccines are biological response modifiers. They prime the immune system to attack the cancer cells in the body. The goal is to prevent or to treat cancer or to prevent it from coming back. Types of vaccines?. Prophylactic cancer vaccines:

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CANCER VACCINES

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  1. CANCER VACCINES

  2. What are cancer vaccines? Cancer vaccines are biological response modifiers. They prime the immune system to attack the cancer cells in the body. The goal is to prevent or to treat cancer or to prevent it from coming back

  3. Types of vaccines? Prophylactic cancer vaccines: these vaccines are intended to prevent cancer from developing in healthy people Therapeutic cancer vaccines: these vaccines treat an existing cancer by strengthening the body’s natural defenses against cancer Potential antigen candidates • Tumor specific antigen: • these are the antigens present only on tumor cells. they • are unique as they are produced as a result of • somatic mutations in the original sequence of protein • Tumor associated antigen: • these antigens are normally present on tumor cells but are • also present on normal cells

  4. Problems? lack of tumor specific antigens (TSA) weakness of immune responses against tumor associated antigens (TAA) each tumor has different types of cell surface antigens Solution The common solution to all these modalities is the activation of APCs and the stimulation of an antigen specific CTL mediated immune response

  5. Criticism: myelosuppressiveness due to chemotherapy or any other prior treatment advanced stages of cancer can not be treated due to bulky tumor deposits sometimes the progress rate of tumors outpace the immune system lack of immunological data supporting the significant improvements in time to progression and overall survival observed

  6. Targetting the tumors Tumor specific antigen: Advantage: These antigens are ideal for vaccine preparation as many of these proteins have been demonstrated to be essential for tumorigenesis and cancer progression Disadvantage: Most of the mutations identified are unique to each tumor so this would require the development of personalized immunotherapy for individual patients • Tumor associated antigen: Advantage: TAAs are commonly expressed on antigens with same histology and are shared among tumors of different origin. This is useful for designing a generalized vaccine Disadvantage: TAAs are weakly immunogenic due to the tolerance for self antigens acquired by the immune system in its developmental stages

  7. Types of cancer vaccines Tumor cell vaccines: these vaccines are made from actual cancer cells removed during the surgery Antigen vaccines: these vaccines boost the immune system by using only one antigen rather than the whole tumor cell Dendritic cell vaccines: these are developed by removing some immune cells from the blood which are then exposed in lab to cancer antigens. These antigens turn them into dendritic cells and help them grow DNA vaccines: vectors can be given bits of DNA that codes for foreign antigen Vector based vaccines: these vaccines consists of an antigen in bacterial or viral vector

  8. Tumor cell vaccines Distinctive features: different and unknown antigens can be targeted at the same time the immune response is not HLA restricted the variety of both MHC class I and class II epitopes processed is likely to be able to stimulate both an innate (NK cells, macrophages, eosinophils) and adaptive (CD8+ and CD4+ T-cells) • Different forms of tumor cell vaccines: • vaccines can use autologous or allogenic tumor cells • the tumor cells may be modfied for expression of • MHC, costimulatorymolecules,cytokines or used in • combination with adjuvants • the tumor cells can be used in the form of tumor cell • lysates

  9. Mechanism of action the mechanism for priming naïve T-cells in response to whole cell or lysate vaccination is still unclear tumor cells are probably phagocytosed by DCs and cross presented to CD8+ cells by MHC class I molecules in some models CD4+ response seems to be required for effective tumor rejection it is also proposed that a cross priming mechanism mediated by professional APCs is involved in a post vaccination induction of CD8+ T cell responses

  10. OncoVAX (VACCINOGEN) it is composed of autologous irradiated tumor cells, with or without BCG as an adjuvant Its proposed mechanism of action is the presence of delayed cutaneoushypersenstivity response to tumor cells after the third and fourth OncoVAX treatment a multicenter phase III clinical trial, consisting of 254 patients with stage II and stage III colon cancer was carried out on cancer patients after curative resection of primary tumor a 5.8 year median follow up shows 20.4% reduction in risk of disease progression compared to the control group no significant benefit inn stage IIII disease whereas a statistically significant improvement in phase II patients with 41.4% reduction in risk of disease progression an increase in the OS rate of OncoVAX patients was observed

  11. THANKS!

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