In vivo antitumor activity of tumor-infiltrating lymphocytes expanded in recombinant interleukin-2.
A method was described for the generation of cells from tumor-bearing mice; these cells were capable of exhibiting significant antitumor reactivity when adoptively transferred into tumor-bearing hosts. Tumor cell suspensions from a variety of tumors were able to be separated using enzymatic techniques and they were cultured in medium containing recombinant interleukin-2. Activated infiltrating lymphocytes within these tumors expanded; and, by 6-8 days after initiation of culture, lymphocytes predominated and were able to grow to large numbers. The adoptive transfer of these tumor-infiltrating lymphocytes (TILs) made possible mediation of the reduction of established 3-day pulmonary micrometastases from 5 of 7 tumors tested, including two 3-methylcholanthrene (CAS: 56-49-5)-induced sarcomas, one 1,2-dimethylhydrazine (CAS: 540-73-8)-induced colon carcinoma, and the B16 melanoma, all in C57BL/6 mice, as well as the 1660 bladder carcinoma in BALB/c mice. Approximately 2-4 X 10(6) transferred cells were capable of totally eliminating 3-day established metastases. These cells were thus 50 to 100 times more effective than lymphokine-activated killer cells in reducing established metastases; however, they could not be generated from all tumors. The concomitant administration of recombinant interleukin-2 enhanced, by approximately fivefold, the in vivo activity of these cells. The specificity of action of TILs in vivo was different from that determined by classic amputation rechallenge experiments. The tumor-infiltrating lymphocytes that developed this antitumor reactivity appeared to be Thy-1+ and did not bear the asialo GM1 antigen. The potent antitumor effect of these TILs, when transferred in vivo to tumor-bearing hosts, raises the possibility of utilizing similar approaches for the isolation and therapeutic use of lymphocytes with antitumor reactivity from human tumors.
D000818:Animals; D003520:Cyclophosphamide / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D007116:Immunization, Passive; D007376:Interleukin-2 / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000556:secondary; D008214:Lymphocytes / Q000145:classification / Q000276:immunology*; D008222:Lymphokines / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D011994:Recombinant Proteins / Q000627:therapeutic use
D007376:Interleukin-2; D008222:Lymphokines; D011994:Recombinant Proteins; D003520:Cyclophosphamide