Marrow-Infiltrating Lymphocytes

疾病复发是自体和异体移植治疗失败的最常见原因 (ALIO)血液和骨髓移植(BMT)。因此，增加抗肿瘤药物的需求尚未得到满足。 在这些设置中的豁免权。我们提出了一种新的过继细胞疗法(ACT)来增强 利用自体骨髓移植后的抗肿瘤免疫和治疗异基因骨髓移植后的复发 骨髓作为大多数血液病的主要解剖部位的独特特征 恶性肿瘤和一个富含肿瘤反应性骨髓浸润性淋巴细胞(MIL)的隔室。我们 假设体外激活的肿瘤特异性MIL可以提供可测量和可持续的抗肿瘤作用 收养转移时的豁免权。这一假设是基于我们的初步数据，并通过 将在上一个供资周期中制定的创新战略结合起来。MILs来自多个 骨髓瘤患者可在抗CD3/CD28刺激下体外扩增并显著激活 提高其在ACT研究中的肿瘤特异性。同样，从接受allBMT的患者获得的MIL 使用基于PTCy的GVHD预防也可以扩展，使用相同的技术和增强 它们的抗肿瘤反应性。因此，在具体目标#1中，我们将确定是否组合激活了MILS 使用同种异体骨髓瘤细胞疫苗或来那度胺可以增强和/或维持抗肿瘤免疫 并评价活化的MILs对免疫重建、肿瘤特异性免疫的影响 并将这些参数与临床反应相关联。在具体目标2中，我们将进行一个阶段的L/11 评估从患者那里获得的同种异体ILs作为一种更具肿瘤特异性的临床试验的可行性/安全性

Disease relapse is the most common reason for treatment failure of both autologous (auto) and allogeneic (alio) blood and marrow transplantation (BMT). As such, there is the unmet need to augment antitumor immunity in these settings. We propose a novel adoptive cell therapy (ACT) approach to augment antitumor immunity after autoBMT and to treat the post-transplant relapse after alloBMT by exploiting the unique characteristic of the bone marrow as both the primary anatomic site for most hematologic malignancies and a compartment enriched with tumor-reactive marrow infiltrating lymphocytes (MILs). We hypothesize that ex vivo activated tumor-specific MILs can impart measurable and sustainable antitumor immunity upon adoptive transfer. This hypothesis is formulated on the basis of our preliminary data and by bringing together innovative strategies developed during the previous funding cycle. MILs from multiple myeloma patients can be expanded ex vivo with anti-CD3/CD28 stimulation and activated as to significantly Increase their tumor specificity in ACT studies. Similarly, MILs obtained from patients undergoing alloBMT using PTCy-based GVHD prophylaxis can also be expanded, using the same techniques and augment their antitumor reactivity. Accordingly, in Specific Aim #1, we will determine if activated MILs in combination with an allogeneic myeloma cell vaccine or lenalidomide can augment and/or sustain antitumor immunity after autoBMT and assess the impact of activated MILs on immune reconstitution, tumor-specific immunity and correlate these parameters with clinical responses. In Specific Aim #2, we will conduct a phase l/ll clinical trial to evaluate the feasibility/safety of alloMILs obtained from the patient as a more tumor-specific