Hussain Ahmed, Moxley-Wyles Benjamin, Bryan Michael, Gordon-Weeks Alex, Al-Obaidi Ibrahem, Sandhu Ciaran, Lee Lennard
Medical Sciences Division, University of Oxford, Oxford, United Kingdom.
Department of Cellular Pathology, Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, United Kingdom.
Immunother Adv. 2025 Apr 20;5(1):ltaf016. doi: 10.1093/immadv/ltaf016. eCollection 2025.
Therapeutic cancer vaccines are an emerging class of immunotherapy, but challenges remain in effectively adapting approved vaccines to a growing number of adjuvants, combination therapies, and antigen-selection methods. Phase III clinical trials remain the gold standard in determining clinical benefit, but are slow and resource intensive, whilst radiological surrogates often fail to reliably predict clinical benefit. Using immunological surrogates of efficacy, deployed in 'immunobridging trials', could present a viable alternative, safely speeding up cancer vaccine development in a cost-effective manner. Whilst this approach has proven successful in infectious disease vaccines, identifying reliable immunological correlates of protection has proven difficult for cancer vaccines. Most clinical trials, which present the richest source of data to establish a correlate, rely on peripheral blood samples and standard immunoassays that are ill-equipped to capture the complexity of the vaccine-induced anti-tumour response. This review is the first to outline the importance and challenges of establishing immunological surrogates for cancer vaccines in the context of immunobridging trials, evaluating current immunoassay methods, and highlighting the need for techniques that can characterize tumour-infiltrating lymphocytes and the suppressive tumour microenvironment across a range of patients. The authors propose adapting trial designs for surrogate discovery, including combining phase I/II trials and the use of multi-omics approaches. Successful immunological surrogate development could enable future immunobridging trials to accelerate the optimization of approved cancer vaccines without requiring new phase III trials, promoting faster clinical implementation of scientific advances and patient benefits.
治疗性癌症疫苗是一类新兴的免疫疗法，但在将获批疫苗有效应用于越来越多的佐剂、联合疗法和抗原选择方法方面仍存在挑战。III期临床试验仍然是确定临床获益的金标准，但进展缓慢且资源密集，而影像学替代指标往往无法可靠地预测临床获益。在“免疫桥接试验”中使用疗效的免疫学替代指标可能是一种可行的选择，能够以具有成本效益的方式安全地加速癌症疫苗的研发。虽然这种方法在传染病疫苗方面已被证明是成功的，但对于癌症疫苗而言，确定可靠的免疫保护相关指标却很困难。大多数临床试验是建立相关性最丰富的数据来源，依赖外周血样本和标准免疫测定法，而这些方法难以捕捉疫苗诱导的抗肿瘤反应的复杂性。本综述首次概述了在免疫桥接试验的背景下为癌症疫苗建立免疫学替代指标的重要性和挑战，评估了当前的免疫测定方法，并强调了对能够表征一系列患者肿瘤浸润淋巴细胞和抑制性肿瘤微环境的技术的需求。作者建议调整替代指标发现的试验设计，包括结合I/II期试验和使用多组学方法。成功开发免疫学替代指标可以使未来的免疫桥接试验加速获批癌症疫苗的优化，而无需进行新的III期试验，促进科学进展更快地临床应用并让患者受益。
