Chen L, McGowan P, Ashe S, Johnston J V, Hellström I, Hellström K E
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, Washington 98121.
Cancer Res. 1994 Oct 15;54(20):5420-3.
Tumor cells genetically modified by transduction of B7 (B7-1/CD80), a natural ligand for the T-cell costimulatory molecules CD28 and CTLA-4, can elicit potent tumor immunity, and they can be effective for treatment of established cancers in animal models. In this study, three tumor lines, the EL4 lymphoma, the P815 mastocytoma, and the MCA102 sarcoma were transduced with recombinant retrovirus containing the murine B7 gene, and their potency to induce systemic immunity protective against challenge with wild-type tumor was compared to that of the same tumor cells admixed with the commonly used adjuvant Corynebacterium parvum. While admixture of tumor cells with C. parvum resulted in complete regression of tumors in syngeneic mice, it did not induce protective immunity against a subsequent challenge of wild-type cells from any of the 3 tumors tested. In contrast, B7-transduced EL4 and P815 tumors regressed locally and induced a potent systemic immunity to wild-type tumors and a higher level of cytotoxic T-cell activity than did tumor cells admixed with C. parvum. No systemic immunity was induced by B7-transduced nonimmunogenic MCA102 sarcoma cells. Our results demonstrate that immunogenic tumor cells transduced with the B7 gene are superior to tumor cells mixed with C. parvum for the induction of systemic tumor immunity.
通过转导B7（B7-1/CD80）对肿瘤细胞进行基因改造，B7是T细胞共刺激分子CD28和CTLA-4的天然配体，可引发强大的肿瘤免疫，并且在动物模型中对已形成的癌症治疗有效。在本研究中，用含有鼠B7基因的重组逆转录病毒转导三种肿瘤细胞系，即EL4淋巴瘤、P815肥大细胞瘤和MCA102肉瘤，并将它们诱导针对野生型肿瘤攻击的全身免疫保护的能力与与常用佐剂微小棒状杆菌混合的相同肿瘤细胞的能力进行比较。虽然肿瘤细胞与微小棒状杆菌混合导致同基因小鼠中的肿瘤完全消退，但它并未诱导针对所测试的3种肿瘤中任何一种的野生型细胞后续攻击的保护性免疫。相比之下，B7转导的EL4和P815肿瘤局部消退，并诱导对野生型肿瘤的强大全身免疫以及比与微小棒状杆菌混合的肿瘤细胞更高水平的细胞毒性T细胞活性。B7转导的无免疫原性的MCA102肉瘤细胞未诱导全身免疫。我们的结果表明，用B7基因转导的免疫原性肿瘤细胞在诱导全身肿瘤免疫方面优于与微小棒状杆菌混合的肿瘤细胞。
