HU/SCID MOUSE MODEL: PREDICTING IMMUNOTHERAPY RESPONSES

使用模拟肿瘤的抗独特型抗体的主动免疫疗法- 相关抗原已被证明对动物和 病人。我们提出的研究旨在优化临床 恶性黑色素瘤患者对抗独特型免疫治疗的反应 目前正在IDEC开发。这将通过“独特型”来实现 匹配一组抗独特型抗体中的治疗性抗体 与患者的个人独特型曲目进行比较。我们建议 建立一种定量测定独特型频率的方法- 预期独特型治疗患者的反应性B和T细胞。SCID 小鼠的外周血淋巴细胞将重组 黑色素瘤患者。然后我们将使用脾病灶分析来确定 淋巴细胞对抗独特型单抗的反应频率 抗体。此外，这项SCID脾病灶分析将使我们能够 分析患者的T细胞与辅助性T细胞 回应。这些“独特型匹配”分析将允许肿瘤学家 合理选择抗独特型抗体用于免疫治疗 恶性黑素瘤。

Active immunotherapy using anti-idiotypic antibodies which mimic tumor- associated antigens has been shown to be effective in animals and patients. Our proposed research is aimed at optimizing the clinical response of malignant melanoma patients to anti-idiotypic immunotherapy currently under development at IDEC. This will be achieved by "idiotype matching" a therapeutic antibody from a panel of anti-idiotypic antibodies with the individual idiotypic repertoire of the patient. We propose to develop an assay quantitatively determines the frequency of idiotype- responsive B and T cells in prospective idiotype therapy patients. SCID mice will be reconstituted with the peripheral blood lymphocytes from melanoma patients. We will then use the splenic focus assay to determine the frequency of lymphocytes responsive to anti-idiotypic monoclonal antibodies. Furthermore, this SCID splenic focus assay will allow us to analyze the patient's T cell repertoire with respect to T helper cell responses. These "idiotype matching" assays will allow the oncologist to make a rational choice of anti-idiotypic antibodies for immunotherapy of malignant melanoma.