Cancer Immunotherapies

Question 1

List categories of cancer immunotherapies

Answer 1

1. cytokine based
2. cancer vaccines
3. antibody based
4. engineered T cells

Question 2

What is the goal of cancer immunotherapies?

Answer 2

Enhance the natural immune system mechanisms to target cancer cells

Question 3

What are the categories of cytokine based immunotherapies?

Answer 3

1. Immunostimulatory - often associated with toxicities, low efficacy
2. Hematopoiesis enhancers - to accelerate chemotherapy recovery but tends to be toxic to replicating cells in the bone marrow

Question 4

What is an example of an immunostimulatory cytokine based therapy?

Answer 4

IL-2 administered to patients with advanced kidney cancer or advanced melanoma.
IFN-alpha for some cancers, but low efficacy

Question 5

What are some examples of hematopoiesis enhancing cytokine based therapy?

Answer 5

G-CSF (granulocyte-colony stimulating factor)
GM-CSF (granulocyte-macrophage-colony stimulating factor)
Both are glycoproteins that function as cytokines

Question 6

List categories of cancer vaccines

Answer 6

1. preventative for virus associated cancers

2. therapeutic vaccines that stimulate an immune response to tumor antigens

Question 7

Give an example of a preventative cancer vaccine

Answer 7

1. HPV (cervical cancer)

2. HepB (liver cancer)

Question 8

Give an example of a therapeutic cancer vaccine

Answer 8

BCG (attenuated TB vaccine) - used to treat patients with bladder cancer because BCG can activate anti-tumor immunity by triggering TLR9 receptors.

Question 9

What are some strategies for therapeutic vaccines?

Answer 9

1. Using purified tumor antigens for immunization
2. Whole cell inactivated tumor vaccines
3. tumor derived heat shock proteins

Question 10

What is sipucel-T?

Answer 10

A prostate cancer vaccine derived from a patient’s own dendritic cells that were activated in vitro and loaded with a dominant prostate-specific antigen then transferred back into the patient.
Modest efficacy.
Significant because first and only approved therapeutic cancer vaccine

Question 11

What are the types of antibody based cancer therapies?

Answer 11

1. humanized antibodies
2. conjugated antibodies
3. monoclonal

Question 12

Explain humanized antibodies for cancer therapy

Answer 12

1. they block growth signaling receptors on cancer cells
2. they induce ADCC and complement activation for cancer cell destruction
3. they block angiogenesis to deprive cancer cells of oxygen and nutrients
4. they target immune inhibitory receptors

Question 13

Explain conjugated antibodies for cancer therapy

Answer 13

Antibodies are tagged with toxins or radioactive agents that hone in on cancer cells to deliver poison

Question 14

Explain monoclonal antibodies for cancer therapy

Answer 14

Monoclonal therapies target T cell inhibitory molecules, including CTLA-4 and PD-1 (AKA programmed cell death protein, a T cell surface protein expressed after activation with a function to block further activation)

Question 15

What is PD-1?

Answer 15

Programmed cell death protein.
On the surface of T, B and NK cells
Down-regulates immune system
Promotes self-tolerance by suppressing effector T cell inflammatory activity in peripheral tissues
Binds to it’s ligand - PD-1L, which has broader tissue distribution, including on hematopoietic and non-hematopoietic cells like vascular endothelial, heart, lung, pancreas and skeletal muscle cells

Question 16

What is CTLA-4?

Answer 16

Cytotoxic T-lymphocyte-associated protein
High affinity binding to B7 on APCs
Inhibits further early activation of T cells in secondary lymphoid tissue

Question 17

What is anti-CTLA-4

Answer 17

A humanized monoclonal antibody that blocks CTLA-4 from binding to B7 on APCs, countering the inhibitory effects of CLTA-4 which can lead to enhanced overall immune response
Since they don’t specifically target cancer T cells, they’re associated with autoimmune hypersensitivities
Approved for treatment of malignant melanoma

Question 18

What is CART Therapy?

Answer 18

=Chimeric antigen receptor T cells (CAR T cells)
Genetically engineered hybrid receptor with a cytoplasmic signaling domain with segments from CD3 and CD28 and a tumor antigen specific domain derived from antibody heavy and light chain variable regions.
The artificial receptor is transferred into a sample of a patient’s T cells, giving the T cells the ability to specifically bind to and attack the cancer cells following their transfer back to the patient