Tumor Vaccines in Autologous Bone Marrow Transplantation

自体骨髓移植中的肿瘤疫苗

• 批准号: 6753677
• 负责人: Ivan M. Borrello
• 金额: $ 13.68万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6753677
• 关键词: T cell receptor; antigen presenting cell; autologous transplantation; bone marrow transplantation; colony stimulating factor; genetically modified animals; human subject; human therapy evaluation; laboratory mouse; lymphoma; multiple myeloma; neoplasm /cancer immunology; neoplasm /cancer immunotherapy; neoplasm /cancer vaccine; nonhuman therapy evaluation; patient oriented research

Bone marrow transplantation (BMT) has shown considerable clinical benefit in a variety of hematologic diseases. Nevertheless, a significant percentage of patients will relapse following this procedure. While associated with significant immunosuppression, the BMT setting offers many advantages for the integration of vaccine strategies. Our data show highly efficient transfer of anti-tumor immunity through adoptive transfer, effective anti-tumor responses in the post-BMT prior to full immune reconstitution, and suggest a role of BMT in mediating a delay in tolerance induction. Our first protocol will integrate autologous tumor cells with a GM-CSF-producing bystander cell in the peripheral stem cell transplant setting for multiple myeloma. The trial endpoints will monitor tumor-specific responses to vaccination at various time-points either pre- or post-BMT and determine the correlation of tumor-specific responses with immune reconstitution. Critical to effective responses of GM-CSF vaccines is T cell responsiveness and T cell - antigen presenting cell (APC) interactions. We have shown that T cell tolerance is an early event in tumor progression. Overcoming this barrier offers an attractive opportunity in enhancing vaccine efficacy. The second component of this proposal focuses on the development of future strategies aimed at enhancing the T-cell and antigen presenting cell responsiveness. Integration of these findings into a clinical BMT setting could be easily accomplished and will establish the pre-clinical basis for the next generation of clinical protocols.

骨髓移植（BMT）在多种血液疾病中显示出可观的临床益处。然而，在此程序之后，很大一部分患者将复发。尽管与大量的免疫抑制相关，但BMT设置为疫苗策略的整合提供了许多优势。我们的数据显示，在完全免疫重建之前，通过过继转移，有效的BMT中的有效抗肿瘤反应对抗肿瘤免疫的转移高度有效，并提出了BMT在介导耐受性诱导延迟的作用。我们的第一个方案将使自体肿瘤细胞与多发性骨髓瘤的外周干细胞移植设置中的GM-CSF产生旁观细胞相结合。试验终点将在BMT前后的各种时间点监测肿瘤特异性反应，并确定肿瘤特异性反应与免疫重建的相关性。 GM -CSF疫苗的有效反应至关重要的是T细胞反应性和T细胞 - 抗原呈递细胞（APC）相互作用。我们已经表明，T细胞耐受性是肿瘤进展的早期事件。克服这一障碍为增强疫苗功效提供了诱人的机会。该提案的第二个组成部分着重于旨在增强T细胞和抗原呈现细胞反应性的未来策略的发展。将这些发现集成到临床BMT设置中，可以很容易地完成，并为下一代临床方案建立临床前基础。