Autologous tumor specific immunotherapy of refractory cancers with ex vivo-generated T cells stimulated by autologous tumor cell

摘要

OBJECTIVES: Autologous tumor-cell stimulated cytotoxic T lymphocytes (AuTLs) were prepared from peripheral blood T cells and the T cells were activated ex vivo over a 2-week culturing process in the presence of IL-2 and autologous biopsied tumor-cells from advanced cancer patients. These AuTLs may have potential for efficacy as a locoregional therapy in patients with refractory cancer. METHODS: Twenty-nine of 35 cancer patients (13 esophagus, 5 lung, 3 stomach, 4 breast, 1 melanoma) were enrolled in an early Phase II clinical trial. The patients received direct locoregional intratumoral injection of AuTLs biweekly through medical endoscope or intraarterial infusion reservoir system. Mean 0.25 x 10(9) AuTLs were injected 1 x /2 weeks for 6 weeks. RESULTS: Adverse events related to AuTL were minimal. AuTLs specific for autologous tumor cells were observed in 12 of 29 patients. Seven of these 12 patients (58.3%) had partial response (PR) or stable disease (SD). In contrast, 8 of 23 (34.8%) remaining patients treated by non-specific AuTLs had SD. Infiltration of T effector cells was significantly increased on the biopsied tumor specimens in the immunohistological studies. Furthermore, 11 patients receiving systemic infusion of non-specific LAK/NK T cells without autologous tumor-cell stimulation only had 2 SDs (18.2%). CONCLUSIONS: Our results demonstrated the clinical potential of intra-peritumoral administration of AuTLs. Thus, locoregional immunotherapy with autologous tumor specific AuTLs may be more effective than systemic adoptive immunotherapy using intravenous infusion of autologous tumor non-specific LAK/NK T cells for the treatment of solid cancers.