Biology 207Spring 2004

Biology of Cancer

Lectures 21 and 22: " IMMUNOLOGY AND IMMUNOTHERAPY"

Readings: King Chap. 5; National Cancer Institute, Biological therapies

Scientific American: Immunotherapy for cancer

Outline:

1. Review of immunology

2. The immune system in cancer

3. Fighting off virally caused cancers

4. Cytokine treatment strategies

5. Cancer antigens

6. Monoclonal antibody treatments

7. Cancer vaccines

Lecture:

1. Review of immunology

Immunology--Study of the immune system, which provides protection from foreign invaders.

Natural immunity---Inborn protection from disease.

Acquired immunity--Further protection provided by having cells of the immune system encounter foreign antigens and having these reproduce.

Antigens are proteins or other molecules that can initiate an immune response.

Antibodies are highly specific proteins that recognize antigens.

Humoral immunity--Production of circulating antibodies by B lymphocytes.

Cellular immunity--Different T lymphocyte cells specialize in recognizing foreign cells and assist in response (helper T) or in killing foreign cells (cytotoxic T).

2. Role of immune system in cancer

Ways cancer cells evade the immune system:

--altering their characteristics

--suppressing the immune system

--hiding from the immune response

--outpacing the immune response

Cellular immunity: Many cancer cells are recognized as abnormal and are targeted for cell death.

Key components of process:

--Normal p53 genes in cancer cell; p53 protein regulates genes essential for apoptosis.

--Cytotoxic T cells (T-killer cells)

In metastatic cancer: lose p53 function; cell death pathway not initiated.

Gene therapy: Replace mutant p53 gene with normal gene; restore apoptosis response.

3. Fighting off viral infections: Cancers caused by viruses

a. Cell infected by virus.

b. Some of the viral proteins are broken down by the cell and “displayed” on the cell surface.

c. This display is recognized by cytotoxic T cells that initiate the cell death pathway (=apoptosis) mediated by Fas receptor. Fas receptor binds a growth inhibitor at the cell surface.

d. Tumor viruses often express anti-apoptotic proteins to avoid triggering cell death.

Vaccines to hepatitis B prevent liver cancer; new vaccine against papilloma virus in trials for prevention of cervical cancer.

4. Cytokine treatment strategies: The cancer “cures” of the 1980’s.

Cytokines are growth factors that activate cells of the immune system. Tested as anti-cancer agents that might “wake up” the body’s natural immune response.

Cytokines that have been tested as possible anti-cancer agents:

interferons

interleukins

tumor necrosis factor

Few cancers respond to these treatments when used alone; still some testing done with certain cytokines and in combination therapies.

5. Cancer antigens

--Cancer cells often express new proteins (antigens) on their surfaces or overexpress normal proteins (Her-2 receptor/breast cancer).

--Antibodies made to these proteins can be used for diagnosis or monitoring of some types of cancer.

6. Antibody treatments: “magic bullets” for cancer

--examples: Her-2 for breast cancer, rituxin (CD20 therapy) for non-Hodgkins lymphoma

monoclonal antibody: recognizes one feature of a protein; highly specific; easily mass produced

Drawbacks:

--Monoclonal antibodies are made in mouse cells->immune reaction.

--Takes 10 yrs. to develop these therapies.

Ways these can work on cancer

--block binding of growth factor (Her-2 antibody)

--mark cells so they are targetted for cell death (rituxin)

--bring in a toxic agent or radioactive atom to kill the cancer cells (A33:still in early testing phases)

7. Cancer vaccines:

--Prevent cancer or its spread by sensitizing the immune system to particular proteins expressed on normal cells, but not on cancer cells.

Two types of cancer vaccines

  • Custom vaccines: Individuals are sensitized to the markers on their own tumor cells.
  • Non-patient specific vaccines: cells secrete cytokine (such as GM-CSF) that stimulate body’s immune response to vaccines.A vaccine for pancreatic cancer is being developed at John’s HopkinsUniversity using this approach. See

--Still in research, development or early clinical testing for the following cancers:

breast cancer, prostate cancer (phase III), colon cancer, kidney cancer, melanoma (phase III), non-small cell lung cancer, leukemia, pancreatic cancer

--universal cancer vaccine in development against telomerase (enzyme that replicates ends of chromosomes)

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