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79 Cards in this Set
- Front
- Back
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what is a tumor specific AG, what about tumor associated?
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Tumor Specific (TSA): dont occur on other cells, encoded by tumor genes. Maybe from virus (HPV, EBV, HTLV1) or a BCR in CLL. variant forms of normal genes that have been mutated with carcinogens
Tumor Associated (TAA): not unique to tumor cells. things like fetal genes that are expressed in adult life (AFP-liver, testicular cancer). CEA. colon, lung, breast, stomach. OVER expression. Her2 in breast. PSA in prostate. aid in tumor dx and prognisos |
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in CLL is there a TSA or TAA
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TSA
**all of the same B cells with the same AG that this specific to the tumor **monoclonal transformation of a single B cell so they ALL ahve hte same BCR that is AG |
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there is a mutation that generates a NEW peptide displayed in MCH I
its this TSA or TAA |
TSA
viral proteins or virally induced mutations (chemical, UV) in oncogenes |
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there is inappropriate expression of an embryionic gene
is this TSA or TAA |
TAA
AFP: liver testicular CEA: colon, lung, breast, stomach |
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what are oncofetal AG
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they are TAA
expressed normally in fetus but then it shoutl be transcriptionally silent in adults, we see activation in cancres AFP: liver, testicular CEA: colon, lung, breast, stomach |
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what are AFP and CEA
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TAA, they are fetal AG that are abnormally expressed in adults and associated with cancers
AFP: liver, testicular CEA: stomach, colon, breast, lung |
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what are some examples of TSA
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thse are SPECIFIC to tumors, not found elsewhere
**it can be virally induced (HTLV1, EBV, HPV) **Can be a BCR as seen in CLL (in CLL there is a monoclonal mutation that makes all B cells have the same AG sepcificity) **mutated normal genes. chemical carcinogens, UV light etc |
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we know one category of TAA are oncofetal AG, what other kinds of TAA can we see
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overexpressed, abarrently expressed AG
Oncoproteins like EGF receptor (HER2) is seen in breast cancer and others PSA- normal in seminal fluid and low in plasma, increased with malignancy **its just an overexpression of a normal AG |
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are TAA or TSA helpful in dx and prognosis
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they same TAA (i dont see why TSA couldne also)
there are several canvers associated with AFP and CEA so better for recurrence, prognosis and less for dx |
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there is an overexpression of normal protein expressed in MHC I
TAA or TSA |
TAA
products of oncogenes, EGF R, HER2, PSA |
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CEA is commonly elevated in colon cancer, how is it associated with malignancy, why are CEA levels drawn after resection,
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CEA is a surface cell adhesion moclcuse expressed fetally. when expressed in adult it may help metastisis
CEA is not good for dx bc its also associated with lung, breast, and stomach cancer. BUT after resection it can be used to detect recurrence |
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what cell types can create an IR to tumor AG
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CTL
NK Macrophage |
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what is the main killer for tumor cells
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CTL CD8
**the bind to AG in MHC I and apoptose |
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how do NK kill tumors
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tumors that downregulate MHC are killed with NK
no MCH leads to apoptosis via NK ALSO, NK kill through ADCC, AB dependent |
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how are macrophages used to kill tumors
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T and NK secrete IFNg which recruits macrophages!!!
activated macro help with ADCC, ROI, TNFa |
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what does IFNg do in IR
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T and NK secrete it to call macrophages in
macro does ADCC, ROI, TNFa |
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how do AB combat tumors
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enhance innate immunity
**opsinins to activate compliment and ADCC |
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what activated CLT and NK
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IL2
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CTL recognize TSA and TAA in what MHC ?
what about NK |
MCH I
NK dont need MHC and so are a first line defense. like to kill tumors with LESS MHC I |
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so T and NK secrete IFNg to call out macro, once there what do macro do to combat tumor
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1. ADCC
2. ROI 3. TNFa 4. Present AG to T cells |
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so if a tumor cell is ingested by an APC how can we get CTL
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we know APC uses MHC II nad CLT need MHC I so the APC will cross present
we also need B7 CD28 co stimulation for activation |
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must we have a professional APC for CTL activation
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yep
not sure why, but we need that dendritic cell with cross presentation and a 2 signal for CTL activation |
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waht cancers have evaded the immune system
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any tht have proliforated
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how does the IR actually promote tumor development
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well we kill all of the cells with AG, this leaves some of the FEW cells that dont have AG. essentially we are selectiong for AG negative cell division
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what are 3 things the tumor does to evade the immune system
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1. loose AG: can be endocytosis, shedding, antitumor AB,
2. Decrease MHC 3. Secretion of Immunosupressive things: Prostaglandin E2, TGFb, IL10, FasL |
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if a tumor has less MHC or lost its AG how has it evaded us/
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we cant use T cells to kill it
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what immunosupressive things to tumors secrete
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Prostaglandin E2
TGFb IL10 FasL |
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we know tumors can evade the IR by loosing AG, decreasing MHC, adn secreting immunosupressents. doe the tumor have any other tricks up its sleeve
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1. Sequestering: tumor will grow where the immune system cant get it: eye, testes, ovary, uterus, brain
2. AG Masking: hide AG with lots of carbs that we cant see (T needs peptide) 3. Lack of Co-Stim: not enought APC for presentation, not enough cytokines for CLT to mature. |
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what are the 3 general categories to treat cancer (immuhnotherapy)
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1. Cytokines
2. Monoclonal AB: SPECIFIC 3. Vaccines |
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are cancer vaccines more successful in prevention or treatmetn
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prevention
HPV HBV |
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what is a drawback of using cytokeins for cancer treatemnt
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hard to dose, they create a cascade of events
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what are 2 cytokines that are used to treat cancer and how are they used
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1. IFN: increase MHC I so CTL can see them
2. IL2: activate T cells and NK cells |
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how can we increase MHC I to help kill cancers
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IFN
rIFNa: tx for CML, hariy cell leukemia, follicilar lymphoma, MM, advanced renal cell carcinoma, metastatic melanoma |
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wht does rINFa do for cancer tx
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incerase MHC I
CML, hairy cell leukemia, follicular lymphoma, MM, advanced renal cell carcinoma, metastatic melanoma |
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what is used to activate T and NK cells
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IL2
*LAK: get cells from blood nad then incubate with IL2 and then put back in body *TIL: get cells from TUMOR, incubate with IL2 and then put back |
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so IL2 is great to activate T and NK, what can this cause
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release of lots of secondary cytokines
can be super toxic to the body, this is why dosing is so hard. starts a huge cascade of events |
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what is Aldesleukin
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recombinant form of IL2
tx for metastatic melanoma, advanced renal cell carcinoma |
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what is a more specific way to target the adoptive immune system
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with TIL
get cells FROM the tumor so they are tumor specific CTL ad NK |
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does LAK give tumor specific, why or why not
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NOT specific, mainly NK
they are from plasma, not the tumor Can be good bc tumor can display otehr AG and can also metastisize |
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what is rituximab?
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anti CD20
kills B cells leaves HCS alone bc they dont have CD20, so new B cells can be regenerated |
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what drug targets CD20 with NO radiolabel, what about WITH a radiolabel
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Rituximab
Zevalin |
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what is herceptin
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targers HER2 for breast cancer
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what drug targets breast cancer
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herceptin
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what drug can kill myeloid lineage cells
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campath
CD33 the WBC that ARENT lymphocte **basophile, eosinophil, neutrophile |
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what does mylotarg do
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kills CD33 myeloid cells
Granulocytes, basophiles, neutrophiles AML tx |
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what does campath do?
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targets lymphocytes but not HCS
CLL tx |
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what drug targets lymphoctyes
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campath
CD52 |
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what is zevalin
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radiolabeled CD20
Kill be cells nad some surrounding cells |
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what drug will kill b calls and the cells that surround that b
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zevlin
radiolabeled anti CD20 Bexxar |
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what drug does the same thing as zevalin?
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bexxar
**radiolabeled CD20 to kill the B and the surrounding B's |
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what does avastin do
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tx metastatic colon cancer
vascular endothelium (VEGF) |
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what drug targets metastatic colon cancer
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avastin
*VEGF |
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what does erbitux do
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EGFR1
tx for metastatic colon cancer, squamous carcinoma and HNSCC |
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what class of vaccines are cancer vaccines, whats the basis
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whole cell
**implant a non cancer causing cancer AG, this increases the amt of AG seen so that we can fight it |
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how do whole cell tumor vaccines work
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inject killed tumor cells into the body with non specific adjuvants
this gives the immune system more AG to see to mount its response against. some success with melanoma and renal cell carcinoma |
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what do gene modified tumor vaccines do
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auto tumor cells are mixed with immuno stimulatory genes
IL2, IFNg, B7, GM CSF *we then inject a tumor cell that already has co stimulators on it! |
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what is the vaccine that works by adding co stim molecules to tumor cells and then giving them to the body with some IL2 and otehr stimulatroy molecules
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gene modified tumor vaccines
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what are the immunostimulatory genes used in gene modified timor vaccines
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B7
IL2 IFNg GM CSF **put a costim on the tumor cell and then activate it to get a proliforation/activation of tumor specific T cells |
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whats GVAX
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autologous whole cell vaccine. pts cancer cells are modified to produce GM CSF and returned to pt with prostate or lung cancer
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whats the drug that is a cancer vaccine thta puts GM CSF on a pts tumor cell
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GVAX
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other than T cells what other cell is used in tumor vaccine
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dendritic
((dendrite displayes tumor AG so it can activate T cells |
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if you pulse dendritic cell with tumor AG what are you hoping to accomplish
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activate CTL
**used for prostate nad melanoma |
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dendritic cells pulsed with tumor AG are being used for what cancers
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prostate
melanoma |
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IFNa and g do what in malignant melanoma
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increase MHC I
g also activated NK and Macrophages |
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wht things are combined to make melanoma vaccine
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CD34: stem cell
IL4: dendritic MAGE: the melanoma thing GM CSF: make WBC **make dendritic cells! you cant make them directly so you stim the stem cells and then provide the cytokines for dendritic cells |
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how are dendritic cells make for vaccines? use melanoma tx as an example
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we cant jsut take them from the serum
we use a MAGE (the melanoma AG) and CD34 (HCS) GM CSF and IL4. this aids differentiation of dendritic cells |
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tumor AG incluse TSA, give 2 examples
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1. BCR in pts with CML
2. Viral protein expression in virally indiced tumors |
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what are 4 types of TAA
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AG not specific to tumor
AFP CEA **inappropriate expression of oncofetal AG EGFR PSA *increased level of expression |
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what can detect early recurrence of colon cancer
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CEA monitoring
**a TAA, tumor assoiated AG (inapproiate expression of embryionic gene) |
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what do CTL do in theior IR against tumoes
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direct killing of tumors
most effectiv ewith viral involvement |
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with what tumors are CTL most effective
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can get this direct killing of tumor with viral tumors
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what role does NK cell play in the roleof IR in tumor
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ADCC, direct killing of tumor with decreased MHC I
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hwo do AB play to kill tumors
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opsinization nad ADCC
*helps NK and macrophages |
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what do macrophages do to kill tumors
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ROI
TNFa Opsiniazation/ADCC with the help of AB |
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what are the 2 cytokins usd to tx cancer
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IL2
IFN |
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what does this drug do? what does it tx
1. Rituximab 2. Herceptin 3. Mylotarg 4. Campath 5. Zevalin/Bexxar 6. Avastin 7. Erbitux |
1. Rituximab: CD20: B cell lymphoma, CLL
2. Herceptin: ERFR2 (HER2), breast 3. Mylotarg: CD33. AML 4. Campath: CD52. CLL 5. Zevalin/bexxar: CD20 radiolabel. NHL 6. Avastin: VEGF. Colorectal Carcinoma 7. Erbitux: EGFR1, colon, HNSCC |
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what in a whole cell tumor vaccine
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dead cncer cell
adjuvant |
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whats in a gene modified tumor vaccine
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auto tumor cells
cell lines: IL2, IFNg, B7, GM SCF |
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what an example of dendritic cell pulsed with tumor AG that leads to activation of CTL
malanoma, prostate |
CD34 cells
GMCSF IL4 pulsed with MAGE to tx melanoma Pulsed with PSMA to tx prostate cancer |
