[Conventional chemotherapy combined with the repetitive immune cell transfer for patients with refractory advanced...

In order to take advantage by both the anticancer effects and reconstruction of antitumor immunity, we compared the feasibility of a combination of CTL transfer and chemotherapy (ChT) for patients (pts) with malignant ascites due to carcinomatous peritonealitis of refractory gastric cancer to that of ChT only and/or cellular immunotherapy after failing ChT. A total of 22 pts, 8 underwent only conventional ChT (Group A), 6 performed cellular IT after failing ChT (Group B) and 8 underwent combination therapy (Group C), were enrolled in this retrospective study. ChT was based on conventional conditioning regimen with a standard dose for gastric cancer cases: S-1 (80-120 mg/body) plus paclitaxel (60-80 mg/m2), or CPT-11 (70-80 mg/m2) plus CDDP (80 mg/m2). Autologous tumor cells stimulated with T lymphocytes (AuTL), a kind of CTL, were generated ex vivo from peripheral blood lymphocytes over a two-week co-culturing process with autologous tumor cells separating from the ascites. IT was performed for pts of Group B and C. AuTLs were administered twice prior to ChT for pts of Group C, and were injected 1 x /2 weeks directly into the peritoneal cavity. The treatment was repeated at least three cycles with one-week interval. The mean survival period of Group A, B and C was 8.4, 5.2 and 11.3 months, respectively, and 1 pt in Group A and 3 pts in Group C survived over one year. Adverse events related to both of the ChT and AuTL transfer at all doses were minimal. Ascites had decreased or disappeared in 8 pts in this study. Lymphocytes of ascites were evaluated for cytokine production and subset of CD4+CD25+ T cell before the treatment, and after 3 treatments. The group C pts had increased IFN-gamma and IL-12 production with no TGF-beta1 responses by their ascites after 3 treatments. In contrast, the group A and B had no IFN-gamma, IL-12 or TGF-beta1 responses. These data show that combination therapy of CTL transfer and ChT is a feasible option for patients with refractory peritoneal carcinomatous of gastric cancer without serious adverse events. Although it depends on each mechanism of IT and ChT, a more stringent evaluation of CTL transfer combined with ChT for refractory gastric cancer should be performed.