Immunotherapy in Hematology

Question 1

Describe the normal function of CTLA-4 and how it can be targeted for use in therapy

Answer 1

CTLA-4 inhibits B7. Since B7 is an inhibitory receptor, if we have antibodies to CTLA-4, we are inhibiting the inhibitor, thus activating the T cell and augmenting the body’s natural immune response

Question 2

Describe the normal function of PD1/PD1Land how it can be targeted for use in therapy

Answer 2

APC has PD-L while T cell has PD-1If there is a PD-1 agonist, we can better fight autoimmunity, allergy, transplant rejection, etc. This increases negative feedback and promotes immune toleranceIf we antagonize PD-1, we can better fight cancer and infectious diseases

Question 3

How do tumors escape cellular immunity?

Answer 3

Withdrawing HLA molecules renders them invisible to our T cellsWe can help our T cells to overcome this restriction by using chimeric antigen receptors (CAR)

Question 4

Explain the properties and uses of interferons and cytokines.

Answer 4

Interferons
* Naturally occurring protiens
* Antiviral, antiproliferative, cytostatic, immunomodulatory, differentiating, and inhibitory of cellular genes
* Can act directly on tumor cells as well as effector cells (ex: NK cells, T cells, macrophages)
Cytokines (Interleukins)
* Secreted by white cells
* Involved in cell to cell talk
* Enhance tumor identification
* Enhance tumor cell kill Uses IL2: Renal cell carcinoma Treatment of graft vs. host disease