Chapter 21

Question 1

describe a tumor associated agn. what criteria are critical to differentiate these agn from others and t/f make them a good target for therapy?

Answer 1

tumor agns that can be recognized by the immune system and used as a target for therapy.
The agn are either expressed on the cell surface or intracellular but displayed on MHC. The agns must be tumor specific (product of activated oncogene or mutated oncogene) or can be oncofetal (not expressed by normal adult tissues)

Question 2

give ex of at least 5 TAA in people and 1 well documented in dogs

Answer 2

BCR-ABL, E7 (HPV), tyrosinase, MART1, Her2/Neu

Dogs - PTHrp

Question 3

obviously most cancers dont trigger an IR. What T cell phenomenon is responsible for the lack of IR?

Answer 3

tolerance or anergy

Question 4

gene transfer is accomplished by 2 methods. what are they are what are the +/- of each

Answer 4

physical methods: 100-1000x less efficient. some cells fragile or resistant to this technique

infection w/ virus (transduction)

Question 5

transduction uses many different classes of virus. name at least 2 and +/- of each

Answer 5

RETROVIRUS
insertional mutagenesis, replication defective needs helper virus, efficient process, only infects proliferating cells, can only insert small amt DNA material

ADENOVIRUS
DNA remains episomal, not incorp in to host DNA, generates immune response, transfers genes to replicating AND non replicating cells, efficient. No insertional mutagenesis, only carries small amt DNA, episomes lost from cells in 2-4 weeks.

Question 6

Explain how anti-sense therapy can be used to treat cancer. What are the disadvantages associated w/ this treatment?

Answer 6

Exogenous administration of antisense oligos to interfere w/ gene expression. For optimal effect must get into target cells and enter nucleus. Permeation is low, they are degraded by cellular nucleases, must pick a gene that is preferentially expressed in the cancer

Question 7

describe passive immunotherapy and give 1 example of how this is being used clinically

Answer 7

Includes the use of anti-tumor reagents that have been generated in vitro such as Mab (herceptin) or cytokines (IFN, IL-2)

Question 8

How do interferons work against cancer?

Answer 8

inhibit cell proliferation, increase gene expression, augment proliferation and cytotoxicity of CTLs and NK cells

Question 9

how is IL-2 used for cancer treatment? what is the major disadvantage of this therapy?

Answer 9

stimulates t cell proliferation, NK cells and LAK cells tx of melanoma and renal CA

TOXIC esp causing capillary leak syndrome w/ hypotension, wt gain and edema

Question 10

How is IL-12 used in cancer therapy

Answer 10

mediates anti-tumor activity by helping generate TH cells and NK cells

Question 11

describe adoptive therapy, give example

Answer 11

adoptive transfer of sensitized lymphs

efficacy varies w/ # of cells infused

Question 12

Mabs were initially made in mice but humans could develop an anti-mouse aby response. What are some ways that newer Mab techniques to help avoid this unwanted IR?

Answer 12

Chimeric Abys have a human constant region and murine variable regions - clones only the variable region of the murine heavy and light chain bound to agn, rest of aby is human.

Question 13

How do mabs stimulate an IR in a patient (list 3)

Answer 13

Bind target and mediate lysis of tumor cell through:
1- complement mediated lysis
2- aby dependent cellular cytotoxicity (which is mediated by Mac or NK binding to Fc region of Ab)
3- Aby can bind a receptor for growth factor blocking stimulation

Question 14

what do the following Mabys target?

Rituximab, Bevacizumab, Trastuzumab, Cetuximab

Answer 14

Rituximab - CD20
Bevacizumab - VEGF
Trastuzumab - HER2/neu
Cetuximab (Erbitux) - EGFR

Question 15

Mabs can also be labeled w/ a radioactive component for added cellular toxicity. what type of radiation is used or emitted from these compounds? Gamma or beta?

Answer 15

beta (short distance of penetration)

Question 16

describe active immunotherapy

Answer 16

strategies to generate an anti-tumor response in vivo. requires a tumor associated antigen presented on MHC I or II

Question 17

For a THI immune response, what cytokines are release? what cells are stimulated? what cytokines are released in a TH2 response? what cells are stimulated?

Answer 17

TH1 - release IL-2 and iFNy promoting CTLs

TH2 - secretes IL4, IL10 and supports B cell class switching and humoral response

Question 18

There are 4 major types of functional assays used for immune monitoring in cancer trials. The gold standard for functional detection of activation is called the ___. What does this test tell us?

Answer 18

Elispot.

Measures (quantitatively) correlates w/ CTL function. In some reports it also correlates w/ clinical outcome.

Question 19

TAAs prepared as lysates or purified proteins can be used as vax to stimulate the immune system. What is BCG and how is it used in a tumor vax.

Answer 19

BCG - Bacillus Calmette-guerin is an adjuvant (from bacteria) and can enhance vaccine activity. GM-CSF is also commonly used in this fashion.

Question 20

What is 1 advantage to using a DNA plasmid injection into muscle or other tissue as a way to generate a tumor IR? Explain 1 way that DNA vax have enhanced to produce even better anti-tumor IRs.

Answer 20

DNA plasmids have been documented to express DNA for up to 1 year. Studies have shown immune tolerance can be broken. Can include genes that will encode for genes for cytokines that will direct the type of IR you want.
ex: encode for PSA against the prostate and IL-2 to stimulate T cells

Question 21

Describe what an allogeneic tumor cell vax is and what is 1 major negative to the theory of using this tx against cancer. What is a positive feature of this type of tx?

Answer 21

Allogeneic means from a tumor of the same species but not THAT patient’s tumor specifically. Cells are rendered nonviable such as w/ RT and then given to patient. Problem is that cells are not likely to share same MHC haplotypes so cells cant interact w APCs. Unless the foreign cells are processed as foreign agn and then presented on the p own MHC. The vax may not have the same TAAs as the patient’s tumor. Esp in melanoma.
Positive- easy to make, mass produced, readily available. Not needed from own tumor.

Question 22

What are some disadvantages and advantages of autologous vax?

Answer 22

ADV - will have all the TAAs of that patient’s tumor, will express p own MHC

DIS - difficult to make clinical grade vax for each patient. may not overcome tolerance unless modified or adjuvant added