Combination immunotherapy of cancer

摘要: Abstract The interaction of cancer with the immune system has long been established. Modernapproaches to immunotherapy concentrate on boosting host resistance by vaccines, killer cells or cytokines, such as interleukin-2 interferons. Little attention paid possibility sensitizing tumor mediated attack. non-steroidal antiestrogenic agents, tamoxifen (TX) and toremifene (TO) are widely used for treatment estrogen receptor positive mammary carcinomas other sex hormone dependent tumors. We discovered that TX TO sensitize killing natural (NK), lymphokine activated (LAK) cytotoxic T lymphocytes (CTL). also demonstrated potentiated lethal in syngeneic murine tumor-host system. DBA/2 C3H mice were injected doses subcutaneously. Combination therapy NK, LAK CTL effector antiestrogens could cure up 75% mice. Lymphocytes freshly isolated from ascites patients ovarian had no lytic effect autologous cells. Activation associated (TAL) infiltrating (TIL) hrIL-2 presence induced detectable cytotoxicity most cell cultures. A highly significant increase lysis was found when both target treated antiestrogens. Additional interferon-alpha resulted further enhancement a number cases. It is clear our results capable increasing susceptibility ofhuman lung about 60% cases so examined. Sensitization requires active metabolic participation suggesting amplification programmed death underlying mechanism. Both Fas/Fas-L perforin/granzyme pathways, which can trigger apoptosis, affected This supported observations Fas expression carcinoma Fas-antibody upregulated antiestrogen treatment. In contrast, did not stimulate Fas-L lack correlation between expresion drug kille cytolysis suggest pathway. K562 negative susceptible anti-Fas cytolysis. However, significantly inceased NK total abrogation chelation extracellular Ca++ indicates perforin/grenzyme Similar obtained carcinomas. reder more forkiller destruction, thereby potentiate defence against cancer. On basis combination experiments bearing we now conduct feasibility trials development protocols man.