Adoptive immunotherapy of murine hepatic metastases with lymphokine activated killer (LAK) cells and recombinant interleukin 2 (RIL 2) can mediate the regression of both immunogenic and nonimmunogenic sarcomas and an adenocarcinoma.
The incubation of normal murine splenocytes in recombinant interleukin 2 (RIL 2) gives rise to lymphokine-activated killer (LAK) cells that are specifically cytotoxic to fresh noncultured, autologous, syngeneic, and allogeneic primary and metastatic tumor cells, but are not toxic to normal cells. We have recently shown that the systemic injection of RIL 2 given alone or in conjunction with LAK cells can reduce the number of established pulmonary and hepatic micrometastases from a weakly immunogenic sarcoma in mice. In this report we have analyzed the response of hepatic metastases (HM) induced from both a nonimmunogenic sarcoma (MCA-102) and an adenocarcinoma (MCA-38). Treatment of mice bearing HM from the MCA-102 and MCA-38 tumors revealed that low doses of RIL 2 (5000 to 25,000 U t.i.d.) had little if any anti-tumor effect when given alone (mean percent reduction over control for the MCA-102 tumor: 14%, for the MCA-38 tumor: 10%, p, not significant). Doses of 100,000 U of RIL 2 affected a 38 and 53% reduction in the number of metastases over control for the MCA-102 and MCA-38 tumors, respectively (p less than 0.05). However, when LAK cells were added to the same doses of RIL 2, the corresponding mean percent reduction over control was 90% (p less than 0.005) and 61% (p less than 0.05) for MCA-102 and MCA-38, respectively, at RIL 2 doses of 5000 to 25,000 t.i.d. At doses of 100,000 U of RIL 2 administered with LAK cells, the corresponding percent reductions were 98 and 99%, respectively (p less than 0.005). Therapy with LAK cells plus RIL 2 can also prolong the survival of these mice. In addition, the intraportal administration of LAK cells is more effective than the i.v. administration of these cells. Thus, treatment of established HM from a nonimmunogenic sarcoma and an adenocarcinoma can be successfully mediated by the systemic infusion of LAK cells with RIL 2. These findings provide a rationale for clinical trials of infusion of LAK cells with RIL 2 in the therapy of HM in humans.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004306:Dose-Response Relationship, Immunologic; D007116:Immunization, Passive / Q000379:methods; D007263:Infusions, Parenteral; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology / Q000528:radiation effects / Q000637:transplantation*; D008113:Liver Neoplasms / Q000276:immunology / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000627:therapeutic use; D012513:Sarcoma, Experimental / Q000276:immunology / Q000401:mortality / Q000556:secondary / Q000628:therapy*
D000970:Antineoplastic Agents; D007376:Interleukin-2; D008222:Lymphokines; D011994:Recombinant Proteins