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
CEA location in cancer
expressed everywhere on all levels of enterocytes in the mucosa (not less and less as approach the lumen)
charact of CEA molecule
- 180 kD
- 28 potential N-linked glycosylation sites
- membrane anchored but not transmembrane
conference on CEA epitopes concluded what
CEA is part of a family of molecules called CEACAM (and there are 9 major epitopes of either peptide or glycopeptide structure)
CEA gene structure
- 3 identical repeats
- part of the Ig supergene family
- looks like an Ig gene
function of CEA
- intercellular adhesion
- adhesion of colon wall to bacterial cell surfaces
- stem cell maturation involvement
function of the 18 active genes coding for the CEACAM adhesion molecules
- many different functions (apoptosis, dev, neogenesis)
- function in METASTASIS
what kind of molecule CEA is specifically
tumor ASSOCIATED antigen (not tumor specific bc expressed in small amounts in normal tissues)
ability of screening for cancer with CEA
- can’t do that
- because CEA can be elevated and stable in the blood in many inflam conditions that are benign
meaning of elevated and RISING CEA levels
this occurs in 70% of human cancers (including GIT cancers)
