Treatment of subcutaneous tumor with adoptively transferred T cells.
Adoptive immunotherapy with T cells directed at tumor antigens has been demonstrated to result in the regression of malignant tumors in humans. These encouraging results have prompted the further exploration of parameters necessary to treat tumor in various locations in animal models. We have demonstrated that T cells that are sensitized to tumor antigens and then ex vivo cultured are capable of eradicating pulmonary metastases. In this report, we demonstrate that these T cells are capable of eliminating subcutaneous tumor deposits. Critical to the successful treatment of subcutaneous tumor was treatment with a large number of adoptively transferred T cells and pretreatment of the mice with irradiation. The transfer of T cells from tumor-bearing mice into irradiated mice failed to inhibit the therapeutic effect of ex vivo cultured T cells, suggesting that irradiation was not acting only as an immunosuppressant. Irradiation resulted in increased expression of the F4/80 and 33D1 epitopes on antigen-presenting cells within the tumor. The therapeutic effect of the adoptively transferred T cells was eliminated if either CD4 cells or CD8 cells were depleted. Naive T cells subjected to the same culture conditions were completely ineffective at eliminating tumor. These results demonstrate that adoptively transferred T cells derived from tumor-bearing hosts can treat subcutaneous tumor deposits, and they define the conditions necessary for the elimination of tumor in this location.
Peng
L
L
Center for Surgery Research, Cleveland Clinic Foundation, Ohio 44195, USA.
Shu
S
S
Krauss
J C
JC
D000818:Animals; D017951:Antigen Presentation / Q000528:radiation effects; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D005260:Female; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000494:pharmacology; D012513:Sarcoma, Experimental / Q000276:immunology / Q000628:therapy*; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000637:transplantation*; D014916:Whole-Body Irradiation
D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma