EVALUATION OF CELLULAR AND HUMORAL IMMUNITY AGAINST IDIOTYPE

尽管自体干细胞移植的大剂量放化疗在治疗pts方面显示出一定的前景。对于多发性骨髓瘤，基础疾病的复发仍然是治疗失败的主要原因。这是一项初步研究，旨在探索主动特异性免疫治疗在消除高剂量治疗后残留的微小疾病方面是否有效。pts的实验研究。淋巴瘤患者和单个骨髓瘤患者的研究表明，免疫球蛋白独特型可作为肿瘤特异性抗原，用于开发针对b细胞恶性肿瘤的治疗性疫苗。分。将在高剂量治疗前后的几个时间点用骨髓瘤独特型蛋白免疫，通过结合载体（KLH）和GM-CSF作为免疫佐剂给予免疫原性。本研究的目的是测试细胞和体液免疫是否可以诱导针对骨髓瘤患者移植前和移植后表达的独特独特型。分。在高剂量美法兰/TBI或美法兰/环磷酰胺治疗后，再进行自体外周单核干细胞移植，接受连续4天、2、3和6个月的骨髓瘤Id-KLH （0.5 mg）接种s.c.与GM-CSF （250 |g/mg2）。18分。都接受过治疗。所有的分。已经证明了对KLH的应答，这表明由BMT调理方案产生的免疫抑制不是BMT后主动免疫的障碍。更进一步，超过50%的分数。已经证明了t细胞对独特型的反应，正如体内自身独特型特异性产生细胞因子和/或独特型特异性皮肤试验反应性所证明的那样。-人体实验对象

Although high-dose chemoradiotherapy with autologous stem cell transplantation has shown some promise in the management of pts. with multiple myeloma, relapse of the underlying disease remains the primary cause of treatment failure. This is a pilot study to explore the possibility that active-specific immunotherapy may be effective in eliminating minimal residual disease remaining after high-dose therapy. Experimental studies in pts. with lymphoma, as well as a single pt. with myeloma have demonstrated the feasibility of immunoglobulin idiotype as a tumor-specific antigen for development of therapeutic vaccines against B-cell malignancies. Pts. will be immunized with myeloma idiotype protein, made immunogenic by conjugation to a carrier (KLH) and administration with GM-CSF as an immunological adjuvant, at several timepoints before and after high-dose therapy. The objective of this study is to test whether cellular and humoral immunity can be induced against the unique idiotype expressed on the patients myeloma pre- and post-transplantation. Pts. will receive a series of 3 vaccinations with myeloma Id-KLH (0.5 mg) administered s.c. together with GM-CSF (250 |g/mg2) for 4 consecutive days 2,3,and 6 months after high-dose therapy with either melphalan/TBI or melphalan/cytoxan followed by autologous peripheral mononuclear stem cell transplantation. 18 pts. have been treated on this study. All pts. have demonstrated responses to KLH, suggesting that immune suppression pro- duced by the BMT conditioning regimen is not an obstacle to active immunization post-BMT. Further- more, 50% of the pts. have demonstrated T-cell responses to idiotype, as demonstrated by autolo- gous idiotype- specific production of cytokines and/or idiotype-specific skin test reactivity in vivo. - Human Subjects