Long-term survival of adoptively transferred tumor-infiltrating lymphocytes in mice.
We examined the long term survival of adoptively transferred, cultured tumor-infiltrating lymphocytes (TIL) in sublethally irradiated nontumor-bearing mice. TIL were produced by culturing Thy-1-enriched single cell suspensions from a variety of murine tumors in exogenous IL-2 along with irradiated tumor cells and splenocytes. TIL were adoptively transferred i.v. to mice and such animals demonstrated a statistically significant degree of protection from a subsequent i.v. tumor challenge. This protection lasted up to 6 wk and occurred in the absence of exogenous IL-2 administration in vivo. Using congenic B6.PL Thy-1 alpha/CY mice we demonstrated directly that TIL can survive in vivo for up to 6 wk and that the adoptively transferred TIL were the source of the relative immunity to subsequent tumor challenge. We conclude that TIL contain cells with substantial functional longevity in vivo even in the absence of exogenous IL-2. These studies are relevant to ongoing clinical trials of TIL as a therapy for patients with advanced cancer.
Alexander
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RB
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Rosenberg
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SA
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D007116:Immunization, Passive; D007165:Immunosuppression Therapy / Q000379:methods; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012513:Sarcoma, Experimental / Q000276:immunology; D018800:Thy-1 Antigens; D014916:Whole-Body Irradiation
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D007376:Interleukin-2; D018800:Thy-1 Antigens