Overview of the immune response to tumors and immunotherapy Flashcards
What are some general categories of tumor antigens?
mutated proteins, viral antigens expressed by virus associated tumors, cancer/testis antigens, over expression or abnormal expression of cellular proteins, differentiation antigens
What is the biggest challenge when trying to eliminate a tumor?
the tumor is self (created by cells from the organism), and we are tolerant to self
What are the important innate cellular immune response to tumor cells?
NK cells and macrophages
How do NK cells recognize cells to kill by?
decreased MHC I presentation, the binding of stress proteins, ADCC (bound antibody to tumor)
What are M1 macrophages activated by?
interferon gamma
How do macrophages kill tumor cells?
via cytokines, lysosomal enzymes, and nitric oxide and oxide radicals
What are important adaptive cellular immune response mechanisms that contribute to killing tumor cells?
host APCs take up tumor cells to present to MHC I and II, CTLs, and T-helper 1 cytokines
What is the role of antibodies in killing tumor cells?
they do not actually do the killing, but they mark the cell to be killed
What are the three ways that tumor cells evade being detected by the immune system?
tolerance, inhibition of T cell activation, lack of T cell recognition of the tumor
How do tumor cells inhibit T cell activation?
with PDL1
How do monoclonal antibodies work?
monoclonal antibodies bind to PD1 or PDL1 to block the inhibition of T cell activation and allow CTLs to kill
What type of ‘vaccine’ is the canine melanoma vaccine?
xenogeneic DNA vaccine
What is the tumor antigen that canine melanoma vaccine targets?
tyrosinase
How does the canine melanoma vaccine work?
the human tyrosinase gene is inserted into a bacterial expression plasmid, the tyrosinase protein is made and presented on both MHC I and MHC II which are then recognized by CTLs and TH cells as foreign because the trosinase is human, and there is enough simularity that they attack both the human and canine tyrosinase in the dog