Tumour Immunology And Immunotherapy

Question 1

Describe the basis (summary) of immunosurveilance and the evidence that supports

Answer 1

Certain tumours can express antigens that are absent from corresponding normal tissues and so the immune system detects the abnormally expressed antigen and launches an attack as an autoimmune destruction of normal somatic tissues.

Malignant cells are generally controlled by the action of the immune system. The evidence that supports how the immune system controls malignancy is:

1. Autopsy shows cancerous cells but the individual showed no symptoms
2. When transplanting a melanoma arises
3. Deliberate immunosuppression increases risk of malignancy
4. Men are more likely to die of malignancy because they have weaker immune system

Question 2

How does the immune system control cancer

Answer 2

1. The release of cancer cell antigens (cancer cell death)
2. These antigens are captured by APCs like dendritic cells which migrate to lymph node
3. If the environment is sufficiently inflammatory and there is enough costimulation then you will get an activation of the T-cell response which will bring antibody response
4. T cells will travel via blood (intracellular) back to tumour
5. T cells activated and infiltrate tumour (TIL)
6. Recognition of cancer cells by T-cells
7. Killing of cancer cells

Question 3

Describe cancer pathogenesis of tumours

Answer 3

Initiation of cancer usually result from multiple sporadic complications events over time. Aberrant regulation of apoptosis and the cell cycle results I. Tumour growth.

Tumour cells don’t have lots of inflammation so more likely to be missed by immune system, once there is sufficient inflammation there will be sufficient recruitment of inmate immune cells and thus expression and recognition of tumour antigens.

Question 4

What are the problems in immune surveillance of cancer

Answer 4

1. It takes the tumour a while to cause local inflammation

2. Antigenic differences between normal and tumour cells can be very subtle

Question 5

What is cancer immunotherapy

Answer 5

Patients who have cancer will not have generated a good immune response to tumour cells, there hasn’t been enough inflammation trigger antigens, immunotherapy conditions a patients immune system to stimulate a response.

Question 6

What are the cancers of viral origin and which antigens are they associated to

Answer 6

Opportunistic malignancy - immunosuppression

EBV - lymphoma
HIV - HIV
HPV - cervical cancer (induced and maintained by E6 AND E7 Oncoprotiens of HPV

Question 7

What are the problems with targeting associated auto antigens for immunotherapy

Answer 7

1. Auto immune response against normal tissue

2. Immunological tolerance (normal tolerance to auto antigens and tumour induced tolerance)

Question 8

What are the approaches to tumour immunotherapy

Answer 8

1. Antibody based
2. Therapeutic vaccine
3. Immune checkpoint blockade
4. Adoptive transfer of immune cells
5. Combination

Question 9

What are the monoclonal antibody based therapy

Answer 9

1. Naked eg trastuzumab anti HER2, anti CD20, anti CD52 and antiEGFR
2. Conjugated eg radioactive particle. Anti cd20
3. Bi specific antibodies - genetically engineered to combine 2 specifities eg anti CD3 AND CD19