Xu W, de Zoeten E, Carr-Brendel V, Cohen E P
Department of Microbiology and Immunology (M/C 790), Chicago, IL 60612, USA.
Cancer Immunol Immunother. 1998 Jan;45(5):217-24. doi: 10.1007/s002620050436.
Tumor-associated T cell epitopes are recognized by T cells in the context of determinants specified by class I loci. Since the rejection of foreign histocompatibility antigens is known to enhance tumor immunity, immunization with a cellular vaccine that combined the expression of both syngeneic and allogeneic class I determinants could have important immunological advantages over a vaccine that expressed either syngeneic or allogeneic determinants alone. To investigate this question in a mouse melanoma model system, we tested the immunotherapeutic properties of B16 melanoma x LM fibroblast hybrid cells in C57BL/6J mice with melanoma. Like C57BL/6J mice, B16 cells expressed H-2Kb class I determinants and (antibody-defined) melanoma-associated antigens. LM cells, of C3H mouse origin, formed H-2Kk determinants along with B7.1, a co-stimulatory molecule that can activate T cells. The B16 x LM hybrid cells co-expressed H-2Kb and H-2Kk class I determinants, B7.1 and the melanoma-associated antigens. C57BL/6J mice with melanoma, immunized with the semi-allogeneic hybrid cells, developed CD8-mediated melanoma immunity and survived significantly (P < 0.005) longer than mice with melanoma immunized with a mixture of the parental cell types. The failure of melanoma immunity to develop in mice injected with the mixture of parental cells indicated that co-expression of the immunogenic determinants by the same cellular immunogen was necessary for an optimum immunotherapeutic effect. Augmented immunity to melanoma in mice immunized with the semi-allogeneic hybrid cells points toward an analogous form of therapy for patients with melanoma.
肿瘤相关T细胞表位在由I类基因座指定的决定簇背景下被T细胞识别。由于已知对外源组织相容性抗原的排斥可增强肿瘤免疫，因此与仅表达同基因或异基因决定簇的疫苗相比，用同时表达同基因和异基因I类决定簇的细胞疫苗进行免疫接种可能具有重要的免疫学优势。为了在小鼠黑色素瘤模型系统中研究这个问题，我们在患有黑色素瘤的C57BL/6J小鼠中测试了B16黑色素瘤x LM成纤维细胞杂交细胞的免疫治疗特性。与C57BL/6J小鼠一样，B16细胞表达H-2Kb I类决定簇和（抗体定义的）黑色素瘤相关抗原。源自C3H小鼠的LM细胞与可激活T细胞的共刺激分子B7.1一起形成H-2Kk决定簇。B16 x LM杂交细胞共表达H-2Kb和H-2Kk I类决定簇、B7.1和黑色素瘤相关抗原。用半同种异体杂交细胞免疫的患有黑色素瘤的C57BL/6J小鼠产生了CD8介导的黑色素瘤免疫，并且存活时间明显（P < 0.005）长于用亲本细胞类型混合物免疫的患有黑色素瘤的小鼠。用亲本细胞混合物注射的小鼠未能产生黑色素瘤免疫，这表明同一细胞免疫原共同表达免疫原性决定簇对于最佳免疫治疗效果是必要的。用半同种异体杂交细胞免疫的小鼠对黑色素瘤的免疫力增强，这为黑色素瘤患者提供了一种类似的治疗形式。
