cancer immunology Flashcards
what is used in the basics of immunology
inbred mice for 20 generations
what are tsta
tumor specific transplatation antigens
how does tumor transplantation work
you take a tumor and you induce it in the mice
-take out the tumor
-cut it into lil pieces and give it to the mice
-it will survive
what is putitative
generally considered or reputed to be
what is coley’s toxin
basically a mix of attenuated bacteria that he injected in patients that had neck and head tumors and he observed a regression of the tumor that he said was cured
cancer vaccines had what in them
it involved exposure of patients own lymphocytes and or dendritic cells to her tumor cells after removal of that tumor at surgery
what was hoped with cancer vaccines
that such exposure would then further stimulate an expand the already putitatively cancer activated debdritic cells and or t lymphocytes
-these cells were then reinfused into the patients often with significant regressionb of the tumor
name one cancer vaccine
dendreons provenge which has been employed in the treatment of prostate cancer with some success
who and when discovered humoral antibodies
in the 70’s kohler and milstein
what is one of the most successful monoclonal antibody therapies
herceptin
widely used in her2 positive breast cancers
what is rituximab
-monoclonal anti b cd20 lymphocyte antibody
-used with significant success in b cell leukemias and lymphomas
is pro-inflammatory cytokines a sly for cancer treatment in nivo
it fucks u up
Which cytokines are used in cancer therapy
-infa, tnf1 and il2
whar does the in vitro thing do for cytokine treatmnet of cancer
avoids the significant adverse side effects seen in vivo therapy by expanding the putative anti tumor t cell population which is then re-infused into the patient
what are the molecules used in checkpoint inhibition blockade
ctla4 and pd1
what happens in checkpoint inhibition blockade?
hese molecules normally interfere with the
activation linkage that occurs between dendritic cells and CD4-positive helper T
(Th) cells that initiate immune reactivity. Hence, by using monoclonal
antibodies against either CTLA4 or PD1, any ongoing anti-tumour immune
response is allowed to go forward without inhibition.
what does ipilimumab block
-it blocks ctla4 which usually blocks co stimulation
what is a bispecific t cell engager
basically hald an antibody that binds to cd3 and the cea
true or false: engineered cart t cells are expensive
true, it’s super expensive because they are engineered for the person
what is the poliovirus cancer treatment
-pvs ripo
what does pvs ripo do
it has been shown to infect glioblastoma tumors through cd155/necl5 binding (oncofetal molecule), signaling the immune system to destroy the tumor
what is an oncofetal molecule
it is a molecule that is supposed to only be present when you are a kid but is present when you have a cabncer ex: cea or afp
what are the 3 tumor markers
-out of place
-out of wack
-out of time
example of out of place
-paraneoplastic syndromes ex: acth and adh
-chromosomal translocation
example of out of wack
over production ex: m peak of multiple myeloma
what are tumot specific antigens
they appear on the surface of most and perhaps all cancer cells as a consequence of the malignant transformation
application of tumor markers
detection
diagnosis
monitoring
classification
staging
pathology
localization
therapy
deficiencies in early immunologic studies
-lack of adequate control tissues leading to the inability to differenciate tumor specific from individual specific antigens aka allogens
-production of antihumor antisera by only one technique aka antiserum absorbtion
-only one or 2 procedures were employed for the demonstration of tumor specific antigens
correcting the deficiencies
-the study of colorectal cancers where both tumor and normal tissues could be obtained from the same patients
-the production of antitumor antisera by the use of both: immunologic tolerance and immunologic absorbtion
-the use of multiple procedures to detect antitumor antibodies ex: immunoprecipitation. passive hemagglutination, immunofluorescent labeling and immunoelectrophoresis
what is the tolerance technique
inject in rabbit normal bowel tissue extract
-inject sane patient just cancer bowel tissue 3 months later
-bleeding for tumor specific antiserum
what is the absorbtion technique
-inject patient sick tissue in bunny
-bleed for anti tumor antiserum
-put the normal tissue extract in the anti tumor antiserum
how were cea names
-they analized tissues from the colon cancer
-some constituents found in fetal and embryonic gut/pancreas/liver in the first 2 trimesters of gestatoon
-so they called it carcinoembryonic antigens
who identified cea and when
phil gold and samuel freedman in 1965
true or false: most science in cancerbiology is reproducible
false it is not
what is the reproducibility project aka with jocelyn kaiser
it is a an ambitious ooen science effort to test if the key findings in top journals can be reproducible and everyone agreed that it was not reproducible
true or false: there is more cea in cancer
true
what is the chemistry of the cea molecule
-molecular mass 180 kd
-carbohydrate side chains constitute over 50% of the molecular mass with 28 potential N linked glycosylation sites
-a membrane glycoprotein probably membrane anchored rather than transmembrane in nature
cea: -carbohydrate side chains constitute over 50% of the molecular mass with … potential N linked glycosylation sites
28
who made the monoclonal antibody technology
kohler and milstein
basically you fuse b lymphocytes with myeloma cells and you get hybrids and then you get monoclonal antibodies
what is the consensus conference on cea epitopes
-9 major epitope of either peptide or glycopeptide structure
-cea is one of a family of molecules ceacam
what is the structure of the immunoglobulin like superfamily if ceacam genes
3 large amino acids stuck together
how many genes in the cea gene family
29
18 active and 11 pseudogenes in 2 cluster at chromosome 19q13.1
what are the primary functions of cea
-intercellular adhesion: reciprocal 2 point adhesion, interaction with integrins and fibronectins
-adhesion between bowel cell mucus-bacterial surfaces
-activity in stem cell maturation-positive or negative
true or false: many of the 18 active genes code for adhesion molecules ceacams with one function
false iut is with varying functions for different members in a myriad of ideas of areas like function in metastasis, insulin metabolism and apoptosis
what is the number of cea bound to an antibody with the standard cea
when you have a ratio abpve 10
true or false: cea is tumor associated not tumor specific, since it is founbd in small amounts in normal tissues
true
true or false: cea is a screening test
false it is not a screening test since elevated but stable, blood levels may be found in a variety of inflammatory
elevated and rising levels of cea are found not only in….
gastrointestinal cancers but may be found in 70% of all human cancers
asco guidelines for colorectal cancer
-useful giude for pre op staging, surgicalplanning and chemotherapy
-quaterly monitoring for 3 years for patients with dukes stages 2 and 3 of colorectal cancer who have had surgery or chemotherapy
national comprehensive cancer network
-serial testing for 5 years in patients with T2 or higher disease if patient may be candidate for resection or isolated metastases in the future
-the pattern of cea decline post op an indicator for the need of adjuvant chemotherapy or second look surgery
5 years prospective study- pre operative cea levels us a….
predictor of subsequent disease free interval
true or false: cea is an independant pronostic factor
true
major roles in monitoring, staging and pronostic of cea
-asco guidelines for colorectal cancer
-national comorehensive cancer network
-american joint comission on cancer
what is the role of carcino embryonic antigen
aid in management and pronostic used in immuno assays and is fda approved
cea as a target
-1. Radioactive monoclonal anti-CEA therapy (RAIT) +/- chemotherapy (e.g. prior to hepatic metastasis resection)
2. Pentacea (bispecific anti-CEA and radioactive molecular receptor) in lung cancer
3. Vaccinia virus/Fowlpox-CEA/MUC1 immunization +/- B7.1, ICAM-1 and LFA-3 (TRICOM)
4. Anti-CEA antibody directed enzyme prodrug therapy (ADEPT)
