TUMOR VACCINES

描述：(由申请人提供)许多证据表明，反- 肿瘤免疫反应对肿瘤的治疗效果有重要影响 骨髓移植治疗血液病 恶性肿瘤。事实上，在以下情况下观察到的降低的复发率 与其他治疗方式相比，异基因移植 这很可能是免疫介导的“移植物抗肿瘤”效应的结果。 不幸的是，由于同种异体反应缺乏肿瘤特异性， 通过降低复发率所获得的好处会损失在发病率和 移植物抗宿主病的死亡率及其治疗。相比之下， 自体移植具有相对有利的安全性，而 保留化疗/放射治疗的益处，剂量超过所能承受的范围 在没有干细胞支持的情况下给予。相应地，增强抗肿瘤的作用 自体移植期间的免疫可能提供了一种减少 没有伴随而来的复发率增加了毒性。在小鼠模型中， 可测量的移植物抗肿瘤效应可以促进T细胞对肿瘤的识别- 相关抗原，而不是宿主次要抗原。然而，这一回应 在移植后阶段迅速消失，与 肿瘤进展。相比之下，在免疫期间接种疫苗 放射自体肿瘤细胞加旁分泌源的重建 GM-CSF的表达维持了这种反应，而这种反应与从 旧病复发。此外，在收集移植物之前进行免疫接种 结果显著地将抗肿瘤免疫过继转移到肿瘤- 生育移植受者。因此，这一总体目标是 建议在增强抗肿瘤免疫反应的背景下 自体外周造血干细胞移植 肿瘤特异性疫苗接种与采用的成功结合 免疫疗法。

DESCRIPTION: (provided by Applicant) Much evidence suggests that the anti- tumor immune response contributes significantly to the therapeutic efficacy of bone marrow transplantation in the treatment of patients with hematologic malignancies. In fact, the reduced relapse rates observed in the setting of allogeneic transplantation when compared to other treatment modalities is likely the result of immune mediated "graft-versus-tumor" effects. Unfortunately, because of the lack of tumor-specificity of the allo-response, what is gained by a reduction in relapse rates is lost in the morbidity and mortality of graft versus host disease and its treatment. In contrast, autologous transplantation has a relatively favorable safety profile, while preserving the benefit of chemo/radiation used at dosed beyond what can be given without stem cell support. Accordingly, effects to augment anti-tumor immunity during autologous transplantation may provide means to diminish relapse rates without concomitant increase toxicity. In mouse models, a measurable graft-versus-tumor effect can upon T-cell recognition of tumor- associated antigens, rather than host minor antigens . However, this response is rapidly extinguished in the post transplant period in association with tumor progression. In contrast, vaccination during the period of immune reconstitution with irradiated autologous tumor cells plus a paracrine source of GM-CSF sustains this response, which closely correlates with freedom from relapse. Furthermore, immunization prior to the collection of the graft results in significant adoptive transfer of anti-tumor immunity to the tumor- bearing transplant recipient. Therefore, the overall objective of this proposal is to enhance the anti-tumor immune response in the setting of autologous peripheral blood stem cell (PBSC) transplantation through the successful integration of tumor-specific vaccination and adoptive immunotherapy.