tumors

Question 1

2 mechanisms of cancer cells to evade immune mediated destruction

Answer 1

1- cancer cells fail to produce or present tumor antigen on their surface and therefore cannot be recognized by T cells
2- secretion of immunosuppressive proteins or expression of inhibitory surface proteins (CTLA-4, PD-1/2)

Question 2

role of cytotoxic T cells vs. tumor

Answer 2

more active against cells that display tumor antigen in MHC

Question 3

role of NK cells vs. tumor

Answer 3

more active against tumors that are MHC-loss variant

Question 4

tumor assoc macrophages (TAMs) and prognosis

Answer 4

poor- breast, ovarian, glioma, lymphoma
better- colon, stomach
others variable

Question 5

CSF1/CSF1R Blockade

Answer 5

reprograms TAMs and improves T cell response

pancreatic CA

Question 6

role of microglia in breast CA mets

Answer 6

microglia will promote colonization of brain tissue by breast CA cells via wnt pathway

Question 7

TAMs and sorafenib

Answer 7

sorafenib is an inhibitor of tyrosine kinases, used in metastatic liver CA; depletion of TAMs enhanced the effects of sorafenib (antimetastatic and anti-angiogenic)

Question 8

describe elimination phase/immune surveillance

Answer 8

when immune cells recognize and kill tumor cells

Question 9

describe equilibrium phase/immunoediting

Answer 9

variant tumor cells arise that are more resistant to killing

Question 10

describe escape phase

Answer 10

1 of the variants may escape killing mechanisms OR recruit Tregs for protection and are able to spread unchallenged

Question 11

2 methods of passive immunity transfer for CA treatment

Answer 11

1- extract tumor specific T cells from patient, expand in vivo and then re-introduce
2- use monoclonal antibodies specific to tumor antigen

Question 12

how do dendritic cell vaccines treat cancer?

Answer 12

tumor antigen is presented to dendritic cell, dendritic cell is re-introduced to patient and T cells against tumor antigen are formed

Question 13

MOA of Provenge

Answer 13

autologous cancer cell vaccine- extract pts DCs, stimulate with combo of PAP/GM-CSF, reintroduce to pt, DCs then stimulate T cells

Question 14

4 problems with antibody directed therapy

Answer 14

1- tumor heterogeneity
2- low density of tumor antigen for extraction
3- human anti-mouse antibody response
4- antibodies must bind every tumor cell (no bystander effect)

Question 15

-omab

Answer 15

fully mOuse

Question 16

-umab

Answer 16

fully hUman

Question 17

-ximab

Answer 17

chImeric

Question 18

-Zumab

Answer 18

hUmaniZed

Question 19

3 mechanisms of “magic bullet” therapy

Answer 19

1- tumor specific antibody, killing by NK cells
2- tumor-spec antibody+toxin
3- tumor-spec antibody+radiation

Question 20

what is ADEPT

Answer 20

antibody directed enzyme/pro-drug therapy

mab-enzyme conjugate/pro-drug given, when deus is metabolized to active form it is cytotoxic at tumor site

Question 21

3 ways to decrease immunogenicity of anti-tumor mab

Answer 21

1- humaize
2- make smaller
3- make bifunctional or fusion proteins (1 molecule with multiple actions)

Question 22

Rituximab

Answer 22

anti-CD20

NH B cell lymphoma

Question 23

Trastuzumab

Answer 23

anti-Her2

her2-neu breast CA

Question 24

Cetuximab

Answer 24

blocks EGFR

colon CA

Question 25

bevacizumab

Answer 25

anti-VEGF + anti-EGFR + chemo

colon CA, glioblastoma

Question 26

ipilimumab

Answer 26

anti-CTLA4

melanoma

Question 27

basis for “transitional” cancer vaccines

Answer 27

irradiated tumor with non-specific activating agent (like BCG), minimal success

Question 28

basis for cytokine CA vaccine

Answer 28

IL-2 given to generate LAK (lymphocyte active killer) and TIL (tumor-infiltrating lymphocytes), failed due to too many Tregs generated

Question 29

how can you generate anti-tumor T cells of a desired specificity for adaptive T cell immunotherapy?

Answer 29

use viral vector to introduce desired TCR a/b chains