Apr5 M1-Cancer Immunology Flashcards
proof of the existence of tumor specific transplantation antigens (TSTA)
- mouse with cancer, resect cancer. it lives
- inject small part of resected cancer to previously sick mouse = it lives
- inject it to healthy sibling = it dies (bc tumor has immunosuppressive quality)
Coley’s toxin is what
- head and neck cancers: Coley would inject a toxin mixture including strep
- pts often die from septicemia
- pts sometimes heal from their cancer
cell-based therapies (vaccines) in cancer immunotherapy def
- take lymphocytes and dendritic cells of pts and expose them to a tumor part resected from surgery
- this stimulates and expands the putatively cancer-activated dendritic cells and lymphocytes
- the 2 cell types are reinjected to fight the cancer
cell-based cancer therapy used in treatment of prostate cancer nowadays
Dendreon’s Provenge
humoral Abs in tx of cancer: who discovered monoclonal Abs + 2 popular monoclonal Ab therapies
- Kohler and Milstein
- herceptin in her2+ breast cancers
- rituximab in B cell leukemias and B cell lymphomas + lupus
pro-inflam cytokines used in cancer therapy + their effect
in vitro or in vivo:
- IFN-a, TNF, IL-2
- effect = expand the putative anti-tumour T cell population
checkpoint inhibitor blockade in cancer immunotherapy
- CTLA4 and PD1 are checkpoint molecules that act to stop the immune response
- use monoclonal Abs to CTLA4 or PD1
2 things that have to happen to APC in lymph node and how it relates to checkpoint inhibition
- MHC+peptide interacts with TCR
- coreception between B7 and CD28
- T cells can express CTLA4 after some time so it binds B7 and so B7 DOESN’T bind CD28
- costim doesn’t occur bc CD28 not bound = no T cell activation
BITE Ab how it works (bispecific T cell engager)
2 Abs sticked together : one against CD3 on T cells, other against CEA Ag on cancer cells
chimeric antigen T receptors (CAR-T cells) how it works
- remove T cells from pts
- grow them in vitro and modify them genetically with a retrovirus so their TCR recognizes specific tumor Ag
- put back at tumor site
example of CAR-T treatment
PVS-RIBO construct (half polio half rhinovirus). not neurotoxic. oncolytic. injected in glioblastomas in the brain. kills tumor cells
3 types of tumor markers and Ags
- ones produced where they shouldn’t be (paraneoplastic syndrome with ACTH, ADH from small cell CA of the lung. also the bcr-abl kinase in CML)
- ones overproduced (M peak of multiple myeloma, Bence-Jones proteinuria and L chain dimers)
- ones produced at moment in life where shouldn’t be (oncofetal antigen like CEA, AFP)
tolerance technique experiments in rabbits
- inject with normal human colon and wait 3 months for them to tolerate it
- inject 3 months later with human CRC (colon cancer) to see if they react to something (would react to cancer Ags only)
conclusion of rabbit experiments with CRC extracts injections
- found a tumor specific Ab in the rabbit that was against the tumor extract ONLY
- this tumor Ag is also expressed in first 2 trimesters of gestation in humans so called it CEA
CEA location in the body and normal distribution in colonic mucosa
- sits in the glycocalyx of enterocytes and so is NOT a transmembrane protein.
- as you go up from BM towards the lumen, enterocytes express CEA less and less
