Anti-idiotype responses abrogate anti-CD4-induced tolerance to a tumor-specific antigen and promote systemic tumor immunity.
Anti-idiotype responses abrogate anti-CD4-induced tolerance to a tumor-specific antigen and promote systemic tumor immunity.
复制标题
抗独特型反应消除抗CD4诱导的对肿瘤特异性抗原的耐受性并促进全身肿瘤免疫。
DOI：
10.1007/s00262-004-0547-3
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Bright,RobertK
中科院分区：
文献类型：
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作者：
Kennedy,RonaldC;Shearer,MichaelH;Lowe,DevinB;Jumper,CynthiaA;Chiriva-Internati,Maurizio;Bright,RobertK
目的：基于免疫的癌症治疗方式是一个活跃的研究领域。这些策略包括被动给药单克隆抗体识别肿瘤相关抗原和主动接种已识别的肿瘤抗原。然而，已经确定了与这些类型的治疗策略相关的几个问题。方法：在本报告中，我们通过采用小鼠实验性肺转移模型和肿瘤抗原接种策略在该系统中诱导完全肿瘤免疫来解决某些问题。利用该模型，我们试图解决与被动给药大鼠单克隆抗cd4诱导的肿瘤抗原免疫无反应性和对被动给药单克隆抗体诱导的抗独特型反应以及对肿瘤免疫诱导的影响相关的问题。结果：被动给药大鼠单克隆抗cd4具有免疫抑制作用，抑制肿瘤抗原免疫抗体的产生，消除肿瘤免疫。反复给药大鼠单克隆抗cd4导致抗独特型反应，可以消除对肿瘤抗原免疫的不反应性，促进全身肿瘤免疫。结论：这些数据检查了与基于免疫的癌症治疗相关的一些潜在问题。这些问题包括对肿瘤抗原的潜在耐受性和建立免疫受损状态，即肿瘤抗原免疫不能产生肿瘤免疫。通过在体内无CD4+T细胞的情况下产生的抗独特型反应靶向抗CD4来消除耐受性T细胞的方法允许非耐受性T细胞的恢复，以及对肿瘤抗原的抗体反应，从而导致肿瘤免疫。
Purpose: Immunologic-based cancer treatment modalities represent an active area of investigation. Included in these strategies are passive administration of monoclonal antibodies which recognize tumor-associated antigens and active vaccination with identified tumor antigens. However, several problems associated with these types of treatment strategies have been identified. Methods: In this report, we address certain issues by employing a murine model for experimental pulmonary metastasis and a tumor antigen vaccination strategy that induces complete tumor immunity in this system. Utilizing this model, we attempt to address issues related to unresponsiveness to tumor antigen immunization induced by passive administration of a rat monoclonal anti-CD4 and the induction of anti-idiotype responses to a passively administered monoclonal antibody and the effects on the induction of tumor immunity. Results: The results presented indicate that passive administration of rat monoclonal anti-CD4 exhibits immunosuppressive effects that inhibit the production of antibodies to the tumor antigen immunization and abolishes tumor immunity. Repeated administration of the rat monoclonal anti-CD4 results in an anti-idiotype response that can abrogate unresponsiveness to tumor antigen immunization and promote systemic tumor immunity. Conclusions: The data examine a number of potential problems associated with immunologic-based treatments for cancer. These problems include the potential for tolerance to the tumor antigen and establishing an immunocompromised state where immunization with a tumor antigen failed to generate tumor immunity. Approaches to eliminate tolerant T cells by targeting anti-CD4 via anti-idiotype responses that could be generated in vivo without CD4+T cells allowed for recovery of nontolerant T cells, and an antibody response to the tumor antigen that results in tumor immunity.