Rod Dunbar 5 Flashcards
How might antibodies to cancer cells be effective?
They could inhibit their binding to other cells preventing metastasis
Label them for uptake by macrophages
Kill them through activation of complement
Label them for killing by NK cells
What is the issue with the immune system developing its own antibodies to cancer cells?
Most extracellular domains in cancer cells are wild type
Most anticancer antibodies are against intracellular proteins most likely due to the large amounts of intracellular proteins not typically exposed to the immune system released by tumour cells which undergo necrosis
How can the paraneoplastic syndromes give insight into patients developing their own antibodies to fight cancer?
In this syndrome antibodies to cancer cells cross react with normal proteins inducing autoimmunity often causing the first sign of cancer in these patients to be neurological
How do antibodies offer a new class of therapeutic agents?
Patients cannot make good antibodies to the extracellular proteins of cancer cells but other animals do allowing us to use them to develop antibodies to antigens
These then have to humanized in order to prevent the patient’s immune system from degrading the drug
What are the target molecules for monoclonal antibody therapies?
They can be anything on a cell surface often being strange and having nothing to do with the cancer process but are simply proteins that are expressed more on cancer cells than normal cells
What role could cytotoxic T cells play in cancer?
They have been proven in animal models to be essential for tumour rejection with recognition of tumours by human CD8 cells being beyond doubt
These can kill cells through the release of granules containing perforin and granzymes, or through the use of TNF-family ligands such as fas-ligand and provide cytokine release which is proinflammatory and anti-angiogenic
What are the two key methods of T cell cancer therapy?
Immunomodulators which increase T cell activity
Direct T cell therapy
How does direct T cell therapy work?
There is generation of highly active and avid lymphocyte cultures in vivo with multiple cultures subcloned and IFN-gamma released causing rapid expansion of a selected lymphocyte population the patients bone marrow is then partially ablated and the lymphocytes infused
How do immunomodulaters work?
They target one of the two checkpoints in the immune tolerance system to prevent lymphocytes effective at killing cancer being killed by this system
Anti CTLA4 blocks the first checkpoint in the lymph node stimulates a new cytotoxic lymphocyte attack while blocking at the second check point (ant PD1) increases the effect of an already existing attack the second checkpoint is a better target as it has less autoimmune effects compared to the first check point
