1. Cytokines
INTERLEUKIN 2
-
not directly cytotoxic - induces and expands a T-cell response cytolytic for tumour cells
- used either alone or with IL-2-stimulated autologous lymphocytes
("lymphokine-activated-killer" or LAK cells; cytokine induced killer or CIK cells)
- cells are produced by obtaining lymphocytes from the patient, culturing them with x-irradiated tumour cells in the prescence of IL-2 and added tumour antigens, and then reinjecting them into the patient with IL-2 - the LAK cells then kill tumour cells but not normal cells
- short half-life (t1/2 = 13 minutes) à either continously infused or given as multiple intermittent daily doses
- side effects of high doses:
- activation and expansion of lytic lymphocytes causes inflammation, vascular leak and secondary release of other cytokines (such as TNF, interferon α) = cytokine storm
- can produce mild/moderate symptoms such as fever/chills, diarrhea and weight gain or hand-foot syndrome (palmar-plantar erythrodysesthesia)
- serious toxicities such as thrombocytopenia, shock, respiratory distress, coma and fatal hypotension