Araki K, Noguchi Y, Hirouchi T, Yoshikawa E, Kataoka S, Silverni L, Miyazawa H, Kuzuhara H, Suzuki C, Shimada Y, Hamasato S, Maeda N, Shimamura Y, Ogawa Y, Ohtsuki Y, Fujimoto S
Department of Medicine, Atago General Hospital, Kochi-shi, Kochi 780-0056, Japan.
Int J Oncol. 2000 Dec;17(6):1107-18. doi: 10.3892/ijo.17.6.1107.
Autologous cancer-specific bulk CTLs are unlikely to be induced by in vitro CTL generation (ivtCTLG) using peripheral blood mononuclear cells (PBMCs) of cancer patients when autologous cancer cells are used as in vitro stimulators. However, autologous cancer-specific bulk CTLs are frequently activated when allogeneic cancer cells are used as in vitro stimulators, regardless of the type of cancer cell. We have developed a cancer-specific immunotherapy called modified CTL therapy, which involves adoptive immunotherapy of autologous cancer-specific bulk CTLs after active immunization of autologous or allogeneic cancer cells screened as in vitro stimulators according to their ability to induce autologous cancer-specific CTLs (ACS. CTLs). Cancer did not regress in patients in whom ACS.CTLs were not induced by ivtCTLG using the patients' PBMCs in therapy. Cancer regression, albeit temporary, occurred solely in patients under the immunological condition that ACS.CTLs were induced by ivtCTLG using PBMCs through the therapy. The induction of ACS.CTLs by ivtCTLG using patient PBMCs in therapy was related to patients' HLA class II antigens. HLA DR8 was seen more frequently in ACS.CTL-inducible patients than in ACS.CTL-uninducible patients (P=0.051). On the contrary, HLA DQ3 was seen more frequently in ACS.CTL-uninducible patients (P=0.055). On the other hand, the success in therapy, albeit temporary, was related mainly to patients' HLA class I antigens. HLA B61 was seen more frequently in patients whose therapy proved effective than in patients whose therapy proved ineffective (P=0.018). HLA Cw7 was seen more frequently in therapy-ineffective patients (P=0.040).
当使用癌症患者的自体癌细胞作为体外刺激剂时，通过体外CTL生成（ivtCTLG）利用癌症患者的外周血单核细胞（PBMC）不太可能诱导出自体癌症特异性大量CTL。然而，当使用同种异体癌细胞作为体外刺激剂时，无论癌细胞类型如何，自体癌症特异性大量CTL经常被激活。我们开发了一种称为改良CTL疗法的癌症特异性免疫疗法，该疗法包括在根据其诱导自体癌症特异性CTL（ACS.CTL）的能力筛选出自体或同种异体癌细胞作为体外刺激剂进行主动免疫后，对自体癌症特异性大量CTL进行过继免疫疗法。在治疗中使用患者PBMC通过ivtCTLG未诱导出ACS.CTL的患者中，癌症并未消退。仅在通过治疗使用PBMC通过ivtCTLG诱导出ACS.CTL的免疫条件下的患者中出现了癌症消退，尽管是暂时的。在治疗中使用患者PBMC通过ivtCTLG诱导ACS.CTL与患者的HLA II类抗原有关。在可诱导ACS.CTL的患者中，HLA DR8的出现频率高于不可诱导ACS.CTL的患者（P = 0.051）。相反，HLA DQ3在不可诱导ACS.CTL的患者中出现频率更高（P = 0.055）。另一方面，治疗的成功，尽管是暂时的，主要与患者的HLA I类抗原有关。治疗有效的患者中HLA B61的出现频率高于治疗无效的患者（P = 0.018）。HLA Cw7在治疗无效的患者中出现频率更高（P = 0.040）。
