腫瘍とくに白血病の免疫化学療法に関する研究

DOI Web Site Web Site

書誌事項

タイトル別名
  • Experimental Studies on Chemo-Immunotherapy against Tumors, Especially those Associated with the Leukemias
  • 腫瘍とくに白血病の免疫化学療法に関する研究--腫瘍細胞の耐性獲得に伴なう抗原性の変化について
  • シュヨウ トクニ ハッケツビョウ ノ メンエキ カガク リョウホウ ニカンスル
  • Antigenic Changes in Tumor Cells Accompanying their Acquisition of Resistance against Anti-Tumor Drug s
  • 腫瘍細胞耐性獲得に伴なう抗原性の変化について

この論文をさがす

抄録

For active chemo-immunotherapy against leukemia, leukemic cells are harvested and stored to be used as immunogen. If, therefore, chemotherapy induces marked antigenic changes in the leukemic cells, an adequate effectiveness of the succeeding immunotherapy cannot, theoretically at least, be expected. From this point of view, the author designed a series of studies on the antigenic changes occurring in tumor cells in concomitance with their acquisition of resistance against anti-tumor drugs. The experimental materials consisted of Donryu rats and Yoshida sarcoma (YS) cells, which are allogeneic to this species. YS strains made resistant t o cyclophosphamide (CPM) (Endoxan) or to nitrogen mustard-N-oxide hydrochloride (NMO) (Nitromin) were examined as to their antigenicity in comparison with the original sensitive strain.<BR>1) Comparison between the antigen icities of the CPM-resistant YS (E-YS) cells and the original YS (S-YS) cells: Rats bearing the E-YS cells survived slightly longer than those bearing the S-YS cells after intraperitoneal implantation of the tumor cells. Following subcutaneous implantation, the growth of the E-YS tumor was slower than that of S-YS tumor, showing a tendency to regress 10 days after implantation, but this regression could scarcely be observed when the hosts had been treated with corticosteroid (βmethasone). The generation time of E-YS cells was found to be shorter than that of S-YS cells. “Weak immunization” studies (subcutaneous implantation of 102 cells) revealed that transplantation immunity was more quickly established with the E-YS cells than with the S-YS cells. Although attempts to demonstrate the specific cell-mediated immune response by the blast formation test or the cytotoxicity test using spleen cells from the tumor-bearing rats proved unsuccessful, seral examination revealed specific cytotoxic activity in vitro against the target cells. Serial estimation of this activity revealed that the titers of the anti-EYS sera rose earlier and reached much higher levels than those of the anti-S-YS ones. This finding was coincident with the growth rates of the subcutaneous tumors produced by cell implantation at the “weak-immunization” rate. On the other hand, no significant difference could be observed between the immunosensitivities of the E-YS cells and the S-YS cells against the cytotoxic sera. These findings seem to suggest that the CPM-resistant YS cells acquired an altered and a strOnger antigenicity compared with the original sensitive cells. Concerning the mechanism of this antigenic alteration, some genetic change in the cells appears to be the most probable, since chromosomal deviation was more frequently detected among the E-YS cells than among the S-YS cells.<BR>2) Comparison between the antigenicities of the NMO-resistant YS (N-YS) and the original YS (S-YS): The N-YS cells were obtained by treating the S-YS with NMO through four generations in vivo. The growths of the subcutaneously implanted N-YS cells were slower than those of the S-YS cells and they tended to regress similarly to the E-YS cells. The cytotoxic activity of the immune sera was more efficiently absorbed by the cells of the same strain as that used for immunization than by those of the other strain, and the titers of the cytotoxic activity of the sera immunized with the N-YS strain rose more quickly than did those immunized with the S-YS strain. These findings suggest, as did the E-YS findings, that the antigenicity of the YS cells are partially altered and intensified, so far as their humoral immunity is concerned, when they become resistant to NMO. Changes in the cytotoxic titers of the sera correlated to considerable extent with the growth curves of the subcutaneously implanted tumors. Cells of both strains, N-YS and S-YS, show ed similar immunosensitivity against the cytotoxic sera. The resu lts of further investigations suggested that

収録刊行物

詳細情報 詳細情報について

問題の指摘

ページトップへ