Ghaneialvar Hori, Jahani Saleheh, Hashemi Elham, Khalilzad Mohammad Amin, Falahi Shahab, Rashidi Mohammad Amin, Majidpoor Jamal, Najafi Sajad
Biotechnology and Medicinal Plants Research Center, Ilam University of Medical Sciences, Ilam, Iran.
Department of Pathology, School of Medicine, University of California, San Diego, USA.
Hum Immunol. 2025 Jan;86(1):111209. doi: 10.1016/j.humimm.2024.111209. Epub 2024 Dec 10.
The field of cancer immunotherapy has experienced remarkable advancements in the treatment of human cancers over recent decades. Therapeutic cancer vaccines have been employed to elicit antitumor immune responses through the generation of specific reactions against tumor-associated antigens. Although preclinical studies have demonstrated hopeful results and at least one product is approved for clinical use, the overall efficacy of cancer vaccines remains restricted. The co-administration of anti-checkpoint antibodies alongside cancer vaccines is proposed as a potential strategy to enhance the clinical efficacy of immunotherapies. Among the various anti-checkpoint agents, monoclonal antibodies targeting CD127, OX40, and CD40 have been further investigated in combined administration with cancer vaccines, demonstrating a synergistic impact on disease outcomes in both animal models and human subjects. This combinational approach has been shown to suppress tumor regression, improve survival rates, and promote the efficacy of cancer vaccines via multiple mechanisms, including the augmentation of generation, activation, and expansion of CD8 T cells, as well as the production of tumor-inhibitory cytokines. Importantly, the impact of the concurrent administration of anti-checkpoint agents and cancer vaccines surpass those observed with the sole vaccine, indicating that this strategy may offer significant advantages for clinical application in cancer patients. In this review, we aim to provide a comprehensive overview of the significance and therapeutic potential of the combined administration of checkpoint agonist/antagonist antibodies and cancer vaccines for human tumors.
近几十年来,癌症免疫治疗领域在人类癌症治疗方面取得了显著进展。治疗性癌症疫苗已被用于通过产生针对肿瘤相关抗原的特异性反应来引发抗肿瘤免疫反应。尽管临床前研究已显示出令人鼓舞的结果,并且至少有一种产品已被批准用于临床,但癌症疫苗的总体疗效仍然有限。将抗检查点抗体与癌症疫苗联合使用被认为是提高免疫治疗临床疗效的一种潜在策略。在各种抗检查点药物中,靶向CD127、OX40和CD40的单克隆抗体已在与癌症疫苗联合给药方面进行了进一步研究,在动物模型和人类受试者中均显示出对疾病结局的协同影响。这种联合方法已被证明可通过多种机制抑制肿瘤消退、提高生存率并增强癌症疫苗的疗效,这些机制包括增强CD8 T细胞的产生、激活和扩增,以及产生肿瘤抑制细胞因子。重要的是,同时给予抗检查点药物和癌症疫苗的影响超过了单独使用疫苗时观察到的效果,这表明该策略可能为癌症患者的临床应用提供显著优势。在本综述中,我们旨在全面概述检查点激动剂/拮抗剂抗体与癌症疫苗联合给药对人类肿瘤的意义和治疗潜力。