ABSTRACT
Observations initially made in the early 1980s indicated that lymphoid cells activated with IL-2 (LAK) could lyse tumor cells and mediate tumor regression in mice. Human clinical trials demonstrated tumor regression in 15-20% melanoma and renal cancer patients treated with IL-2 as well as LAK plus IL-2. Subsequent studies demonstrated that the in vitro stimulation of lymphocytes from tumor-bearing hosts with specific tumor cells as well as the expansion of TIL in the presence of IL-2 could result in the generation of tumor-reactive T cells. Cultured CD8+
lymphocytes could be isolated from patients with a variety of malignancies that recognized autologous as well as allogeneic tumor cells expressing shared class I MHC restriction elements (Darrow et al., 1989; Horn et al., 1991; loannides et al., 1991; Finke et al., 1992). These T cells generally failed to recognize autologous or allogeneic normal cells, and thus appeared to recognize specific tumor antigens in a conventional class I restricted manner, as previously demonstrated in responses against viruses and other foreign antigens (Yewdell and Bennink, 1992). Tumorreactive T cells were found to release IFN-γ, TNF-α and GM-CSF in response to tumor stimulation and mediated tumor cell lysis (Schwartzentruber et al., 1991). In addition, class II restricted CD4+
T cells were identified that released the same set of cytokines as well as IL-2 in response to specific tumor stimulation. Although these cells were more effective than LAK cells at mediating tumor regressions in human clinical trials, complete long-term cures were found in only a small percentage of treated patients.
