title: [Conventional chemotherapy combined with the repetitive immune cell transfer for patients with refractory advanced gastric cancer].
abstract: 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.
authors.affiliation: Dept. of Surgery, Kurume University School of Medicine.
authors.forename: Uhi
authors.initials: U
authors.lastname: Toh
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Fujii
authors.forename: Mai
authors.initials: M
authors.lastname: Mishima
authors.forename: Takuya
authors.initials: T
authors.lastname: Imaizumi
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Koga
authors.forename: Shoujiro
authors.initials: S
authors.lastname: Yano
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shirouzu
authors.forename: Toshiro
authors.initials: T
authors.lastname: Yahara
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yamana
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D002478:Cells, Cultured; D003131:Combined Modality Therapy / Q000009:adverse effects; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010534:Peritoneal Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013274:Stomach Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell