Vanhaelen C P, Fisher R I, Appella E, Ramanathan L
Cancer Res. 1981 Aug;41(8):3186-91.
We have attempted to generate in vitro lymphocytes cytotoxic to a widely studied model of ovarian cancer in C3HeB/FeJ mice. These attempts were unsuccessful with either syngeneic or allogeneic spleen cells. The following experimental results demonstrated that this murine ovarian tumor lacks histocompatibility antigens. (a) Tumor cells were not lysed by allogeneic lymphocytes presensitized to H-2k spleen cells. (b) Tumor cells did not specifically inhibit the cell-mediated lysis of H-2k spleen cells by presensitized allogeneic lymphocytes. (c) Histoincompatible (H-2b or H-2d) and syngeneic (H-2k) mice all died with identical tumor growth patterns within 25, 30, or 35 days following the i.p. inoculation of 10(6), 10(5), or 10(4) tumor cells, respectively. (d) Tumor cells were not lysed by an anti-H-2k antiserum and complement. (e) Absorption of the anti-H-2k antiserum with tumor cells did not decrease the cytotoxicity of the antiserum. (f) Competitive inhibition of a radioimmunoassay and polyacrylamide gel electrophoresis of immunoprecipitate of radiolabeled tumor extracts failed to demonstrate an H-2 heavy chain, although a normal amount of beta-microglobulin was present. This lack of histocompatibility antigens may explain the failure to generate lymphocytes cytotoxic to this tumor. Thus, this murine ovarian tumor, which has a serologically detectable tumor-associated antigen and can be cured by nonspecific immunotherapy, may provide an excellent model for the study of successful immunotherapy in the absence of histocompatibility antigens and associated cell-mediated reactions.
我们试图在体外培养对C3HeB/FeJ小鼠中广泛研究的卵巢癌模型具有细胞毒性的淋巴细胞。无论是同基因还是异基因脾细胞,这些尝试均未成功。以下实验结果表明,这种小鼠卵巢肿瘤缺乏组织相容性抗原。(a)肿瘤细胞未被预先致敏于H-2k脾细胞的异基因淋巴细胞裂解。(b)肿瘤细胞未特异性抑制预先致敏的异基因淋巴细胞对H-2k脾细胞的细胞介导裂解。(c)组织不相容(H-2b或H-2d)和同基因(H-2k)小鼠在分别经腹腔接种10(6)、10(5)或10(4)个肿瘤细胞后的25、30或35天内,均以相同的肿瘤生长模式死亡。(d)肿瘤细胞未被抗H-2k抗血清和补体裂解。(e)用肿瘤细胞吸收抗H-2k抗血清并未降低抗血清的细胞毒性。(f)尽管存在正常量的β-微球蛋白,但放射性免疫测定的竞争性抑制以及放射性标记肿瘤提取物免疫沉淀物的聚丙烯酰胺凝胶电泳均未能证明存在H-2重链。这种组织相容性抗原的缺乏可能解释了未能产生对该肿瘤具有细胞毒性的淋巴细胞的原因。因此,这种小鼠卵巢肿瘤具有血清学可检测的肿瘤相关抗原,并且可以通过非特异性免疫疗法治愈,它可能为研究在缺乏组织相容性抗原及相关细胞介导反应的情况下成功的免疫疗法提供一个极佳的模型。