CAR T Cell therapy Flashcards
What is immunotherapy?
A biological therapy that stimulates or suppresses the immune system to fight cancer, infection and other diseases.
What substances are used?
Cytokines, vaccines, antibodies and engineered immune cells.
How is immunotherapy used in cancer?
Detecting cancer cells using antibodies or engineered immune cells. Targeting proteins on T cells. The fifth pillar of cancer treatment (surgery, chemo, radiation, targeted therapy and immunotherapy).
What are the types of immunotherapy in cancer?
Immune checkpoint inhibitors (CTLA-4 and PD-1), T-cell transfer therapy, therapeutic antibody using monoclonal antibodies, treatment vaccines, immune system modulators.
What is the role of T cells?
Recognise non-self (e.g., bacteria and virus). Receptor on T cells that binds to non self structures. Receptors on T cell acts as accelerators (trigger immune response) and some as brakes (stop immune activation).
What is the evidence that immune T cells can be used as an efficient therapy in cancer?
Efficient immune response after temporal adoptive transfer in mice and regression of melanoma in patients with auto immune disease. Molecular and biochemical advances that identified tumour specific immune responses.
What is the mechanism cytotoxic T lymphocyte antigen 4?
CTLA-4 is expressed on activated T cells and regulatory T cells. CTLA-4 competes with CD28 for binding to B7-1 and B7-2 but CTLA-4 has a much higher affinity. Acts as a break on the immune system.
What is the mechanism of PD1 axis inhibition?
PD (programmed cell death)-1 binds to PD-L1 on target cells e,g., tumour cells. Sends an inhibitory signal to the T cell. Dampens its activation, proliferation and cytokine production. Don’t really get this.
What are limitations of immune checkpoint inhibitors?
Effective initially but relapse, selection pressure (some tumour cells evade immunomodulation recognition) through new pathways. Acquired PD-1 or or anti CTLA-4 treatment may also cause upregulation of other inhibitory receptors.
What are the principles of CAR design and T cell engineering?
T cells or selected T cell subsets from blood. T cell activation and gene transfer. Expansion. Lymphodepletion and infusion CAR T cells.
What are the barriers to CAR T cell therapy for solid tumours?
Immunosuppressive factors, immunosuppressive cells, inhibitory checkpoints, trafficking to tumours.
What are the two categories of cancer vaccines?
Prophylactic and therapeutic.
What are prophylactic vaccines?
Hapaptitis B and human papillomavirus. Against hepaptocellular carcinoma and cervical cancer. Prevent infection by oncogenic viruses.
What are therapeutic vaccines?
Aim to harness the immune system to eliminate cancer cells. e.g., BCG vaccine repurpose for bladder cancer.
What are the adverse effects of cancer vaccines?
Challenges remain because individual tumours can harbour thousands of somatic mutations. Predicting which neoantigens can elicit strong anti-tumour responses remains an imperfect art. Time and cost. Development and production of vaccines takes too long and shortening the time span to personalized treatment is critical.
