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10 Cards in this Set
- Front
- Back
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Objectives
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1. Describe the current view of cancer immunosurveillance, especially the basis of T cell recognition of tumor cells
2. Understand the basis of therapeutic cancer vaccination and recent clinical results that have led to FDA approval of Provenge 3. Describe the potential of CD40 activation in cancer immune therapy, including mechanistic insights from genetically engineered mouse models of cancer 4. Understand the basis of immune checkpoint blockade, in particular CTLA-4 antibodies |
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Principle idea of immune response to cancer?
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1. Immune system uses the same strategies against tumors that it uses to fight infection
2. The immune system remembers |
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Describe cytotoxic recognition of T cells?
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1. Antigens are naturally processed by target cells
2. Peptides from antigen are presented by MHC 3. T cell receptor binding to peptide/MHC complex 4. Recognition leads to lysis of target |
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What are the two signals that prime CTL by antigen presenting cells? Can a tumor cell prime CTL?
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1.
i) Signal 1: TCR: peptide/MHC ii) Signal 2: CD28: B7 2. No, b/c there is no Signal 2, so it is anergic (helpless) |
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What is tumor immunity and the auto-immunity paradigm?
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1. Most tumor antigen are self antigens
2. Vaccines are required to break or overcome tolerance to self-antigens expressed on tumors 3. Expected consequences: tissue specific autoimmunity |
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What are the loading approaches??
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Take out dendritic cells of patient, load them with vaccine, and insert them back into humans
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Phase III study of Dendritic Cells for prostate cancer vaccination: what was the vaccine design? What were the results?
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1. Blood isolated autologous DC loaded ex vivo was PAP-GMCSF fusion protein (Sipuleucel-T/Dendreon). Immunity induced in nearly 100% of patients
2. Randomized double blind placebo controlled Phase III study in men with asymptomatic or minimally symptomatic, metastatic, hormone-resistant prostate cancer (N=512) -Included 3 I.V. vaccinations or placebo over four weeks 2. Results: -Vaccine extended median survival by 4.1 months vs. placebo -Improved 3 year survival by 38% -Minimal side effects |
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CD40 and the T cell hypothesis
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1. Agonist anti-CD40 mAb can substitute for helper T cells
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CD40 mAb-mediated tumor regression in mice depleted of T cells, but no regression in CD40 mediated tumor regression after systemic depletion of macrophages
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True
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Describe T cell infusion
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1. Remove the immune cells from blood
2. Engineer T cells to express chimeria antigen receptors (CAR) 3. Prepare cells for re-infusion 4. Give patient engineered T cells |
