TUMOR VACCINES

说明：（由申请人提供）许多证据表明，抗- 肿瘤免疫应答显著地有助于 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复发率降低 同种异体移植与其他治疗方式相比， 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， 复发率降低所带来的好处在发病率上消失了， 移植物抗宿主病的死亡率及其治疗。 与此相反， 自体移植具有相对有利的安全性， 保留化疗/放疗的益处， 没有干细胞的支持。 因此，增强抗肿瘤的效果 自体移植期间的免疫可提供减少 复发率无伴随毒性增加。 在小鼠模型中， 可测量的移植物抗肿瘤效应可以在T细胞识别肿瘤后， 相关抗原，而不是宿主次要抗原。 然而，这一回应 在移植后迅速消失， 肿瘤进展。 相反，在免疫期间接种疫苗 用辐射的自体肿瘤细胞加旁分泌源重建 的GM-CSF维持这种反应，这与免于 复发 此外，在收集移植物之前进行免疫接种， 导致抗肿瘤免疫显著过继转移至肿瘤， 孕育移植受体 因此，这一总体目标 建议是在以下情况下增强抗肿瘤免疫应答： 自体外周血干细胞移植 肿瘤特异性疫苗接种和过继免疫的成功整合 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.