通过靶向肿瘤相关巨噬细胞的嵌合受体工程化溶瘤病毒重振内源性抗肿瘤免疫
Rejuvenating endogenous antitumor immunity via a chimeric receptor-engineered oncolytic virus targeting tumor-associated macrophages.
我们的研究结果定义了一个精准溶瘤平台,该平台能够解除TAM介导的免疫抑制,同时增强适应性免疫,为癌症免疫治疗提供了一条有前景的转化途径。
英文原题:Durable complete response after combined treatment with tumor-infiltrating lymphocytes and oncolytic adenovirus (TILT-123) in a patient with metastatic mucosal melanoma.
本病例凸显了联合免疫治疗策略作为转移性黏膜黑色素瘤患者一种有前景治疗方案的潜力。
尽管恶性黑色素瘤的治疗取得了显著进展,转移性黏膜黑色素瘤因其复杂的发病机制、独特的病理特征以及对免疫治疗反应有限,仍然是治疗难题。联合不同的免疫治疗方法为解决这些难题提供了潜在策略。TIL(肿瘤浸润淋巴细胞)治疗和溶瘤病毒治疗是有前景的治疗方式,二者可能产生协同作用。患者与方法:我们报告一例48岁女性转移性鼻腔黏膜黑色素瘤患者,在接受多次注射溶瘤病毒TILT-123(igrelimogene litadenorepvec)和单次TIL输注后,在未进行预处理化疗或后处理白细胞介素-2的情况下,获得了持久的完全病理缓解。
免疫组化分析和单细胞测序揭示了治疗过程中注射肿瘤和未注射肿瘤以及外周血中发生的有趣改变,提示TILT-123促进了TIL在肿瘤中的植入,最终导致完全缓解。
BACKGROUND: Despite significant advancements in the treatment of malignant melanoma, metastatic mucosal melanoma remains a therapeutic challenge due to its complex pathogenesis, distinct pathological characteristics, and limited response to immunotherapy. Combining different immunotherapeutic approaches offers a potential strategy to address these challenges. Tumor-infiltrating lymphocyte (TIL) therapy and oncolytic virus therapy represent promising treatment modalities that may synergize with each other. PATIENT AND METHODS: We present a case of a 48-year-old woman with metastatic sinonasal mucosal melanoma who achieved a durable complete pathological response following treatment with multiple injections of the oncolytic virus TILT-123 (igrelimogene litadenorepvec) and a single infusion of TILs, without preconditioning chemotherapy or postconditioning interleukin-2. RESULTS: Immunohistochemical analysis and single-cell sequencing revealed interesting alterations in injected and noninjected tumors as well as in peripheral blood, during the treatment course, suggesting that TILT-123 facilitated TIL engraftment into the tumor, ultimately leading to a complete response. CONCLUSIONS: This case underscores the potential of combined immunotherapeutic approaches as a promising strategy for patients with metastatic mucosal melanoma.
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