Cytotoxic T lymphocytes generated by short-term in vitro TCR stimulation in the presence of IL-4 are therapeutically effective against B16 melanoma.
P14 TCR transgenic CD8+ T cells (LCMV gp33-specific) were activated by antigen in the presence of either IL-2 or IL-2 + IL-4 to generate effector cytotoxic T lymphocytes (CTLs). The therapeutic effectiveness of such IL-2- or IL-2 + IL-4-grown CTLs was tested in mice that had received intravenous inoculations of B16.gp33 melanoma cells 7 days previously. Administration of P14 CTLs activated by antigen + IL-2 + IL-4 was significantly more effective at reducing melanoma colony formation in the lung than those grown in the presence of antigen + IL-2. Highly significant improvement in survival was observed with 80% of B16.gp33-inoculated mice showing long-term survival after therapy with 10 x 10(6) antigen + IL-2 + IL-4-activated P14 CTLs. Similar therapeutic effectiveness of antigen + IL-2 + IL-4-activated P14 CTLs against subcutaneously inoculated B16.gp33 melanoma cells was also found. There was significant reduction in P14 CD8+ T cells in the peripheral blood of B16.gp33-inoculated mice than in mice that did not receive B16.gp33 melanoma cells, indicating possible homing of P14 CD8+ T cells to the site of tumor growth or antigen-induced apoptotic cell death. These results may have implications in tumor therapy using CTLs grown ex vivo, especially during early stages of tumor formation. They also support the concept that the therapeutic effectiveness of CTLs can be governed by the cytokine context in which they are activated.
Institute of Molecular Biology, Academia Sinica, Nankang District, Taipei, Taiwan.
Mei-Ling
ML
Chang
Yi-Ting
YT
Chen
Yu-Chia
YC
Su
John T
JT
Kung
D000818:Animals; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology*; D008168:Lung / Q000276:immunology; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4