Hushmandi Kiavash, Imani Fooladi Abbas Ali, Reiter Russel J, Farahani Najma, Liang Liping, Aref Amir Reza, Nabavi Noushin, Alimohammadi Mina, Liu Le, Sethi Gautam
Nephrology and Urology Research Center, Clinical Sciences Institute, Baqiyatallah University of Medical Sciences, Tehran, Islamic Republic of Iran.
Applied Microbiology Research Center, Biomedicine Technologies Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Exp Hematol Oncol. 2025 May 17;14(1):75. doi: 10.1186/s40164-025-00662-3.
Recent advancements in immunotherapy, particularly Chimeric antigen receptor (CAR)-T cell therapy and cancer vaccines, have significantly transformed the treatment landscape for leukemia. CAR-T cell therapy, initially promising in hematologic cancers, faces notable obstacles in solid tumors due to the complex and immunosuppressive tumor microenvironment. Challenges include the heterogeneous immune profiles of tumors, variability in antigen expression, difficulties in therapeutic delivery, T cell exhaustion, and reduced cytotoxic activity at the tumor site. Additionally, the physical barriers within tumors and the immunological camouflage used by cancer cells further complicate treatment efficacy. To overcome these hurdles, ongoing research explores the synergistic potential of combining CAR-T cell therapy with cancer vaccines and other therapeutic strategies such as checkpoint inhibitors and cytokine therapy. This review describes the various immunotherapeutic approaches targeting leukemia, emphasizing the roles and interplay of cancer vaccines and CAR-T cell therapy. In addition, by discussing how these therapies individually and collectively contribute to tumor regression, this article aims to highlight innovative treatment paradigms that could enhance clinical outcomes for leukemia patients. This integrative approach promises to pave the way for more effective and durable treatment strategies in the oncology field. These combined immunotherapeutic strategies hold great promise for achieving more complete and lasting remissions in leukemia patients. Future research should prioritize optimizing treatment sequencing, personalizing therapeutic combinations based on individual patient and tumor characteristics, and developing novel strategies to enhance T cell persistence and function within the tumor microenvironment. Ultimately, these efforts will advance the development of more effective and less toxic immunotherapeutic interventions, offering new hope for patients battling this challenging disease.
免疫疗法的最新进展，尤其是嵌合抗原受体（CAR）-T细胞疗法和癌症疫苗，已显著改变了白血病的治疗格局。CAR-T细胞疗法最初在血液系统癌症中展现出前景，但由于实体瘤复杂且具有免疫抑制性的肿瘤微环境，在实体瘤治疗中面临显著障碍。挑战包括肿瘤的异质性免疫特征、抗原表达的变异性、治疗递送困难、T细胞耗竭以及肿瘤部位细胞毒性活性降低。此外，肿瘤内的物理屏障以及癌细胞使用的免疫伪装进一步使治疗效果复杂化。为克服这些障碍，正在进行的研究探索将CAR-T细胞疗法与癌症疫苗以及其他治疗策略（如检查点抑制剂和细胞因子疗法）相结合的协同潜力。本综述描述了针对白血病的各种免疫治疗方法，强调了癌症疫苗和CAR-T细胞疗法的作用及相互作用。此外，通过讨论这些疗法如何单独及共同促成肿瘤消退，本文旨在突出可改善白血病患者临床结局的创新治疗模式。这种综合方法有望为肿瘤学领域更有效且持久的治疗策略铺平道路。这些联合免疫治疗策略有望使白血病患者实现更完全、持久的缓解。未来研究应优先优化治疗顺序，根据个体患者和肿瘤特征个性化治疗组合，并开发新策略以增强肿瘤微环境中T细胞的持久性和功能。最终，这些努力将推动更有效且毒性更小的免疫治疗干预措施的发展，为与这种具有挑战性的疾病作斗争的患者带来新希望。
