Gomez-Randulfe Igor, Lavender Helen, Symeonides Stefan, Blackhall Fiona
Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK.
Centre for Drug Development, Cancer Research UK, Oxford, UK.
Ther Adv Med Oncol. 2025 Feb 27;17:17588359251316988. doi: 10.1177/17588359251316988. eCollection 2025.
Therapeutic cancer vaccines aim to generate a robust immune response against tumour-associated antigens (TAAs) or tumour-specific antigens. While their safety is well established, their efficacy as monotherapy remains limited due to factors such as self-tolerance to TAAs and the immunosuppressive tumour microenvironment. Combining cancer vaccines with systemic anticancer therapies (SACTs) offers a promising strategy to improve efficacy. However, the optimal timing and combination with immune checkpoint inhibitors (ICIs) and chemotherapy to enhance immunogenicity are not yet fully understood. This review aims to assess the evidence regarding the immunogenicity of antiviral and anticancer vaccines when combined with SACTs, including chemotherapy and ICIs, with a particular focus on the timing of vaccine administration relative to SACT. Additionally, we evaluate the impact of steroids on immunogenicity. Our findings suggest that the timing of vaccine administration is critical, with improved immunogenic responses observed when vaccines are administered at nadir (15 days post-chemotherapy). Certain chemotherapies, such as low-dose metronomic cyclophosphamide and paclitaxel, demonstrate potential for immunomodulation, enhancing T-cell responses when combined with vaccines. Conversely, steroids may reduce immunogenicity. The combination of ICIs with cancer vaccines shows evidence of a synergistic effect, with concurrent administration generally yielding better outcomes than sequential approaches. Prospective trials exploring various timings and sequences are essential to optimize the efficacy of anticancer vaccines.
治疗性癌症疫苗旨在引发针对肿瘤相关抗原（TAAs）或肿瘤特异性抗原的强大免疫反应。虽然其安全性已得到充分证实，但由于对TAAs的自身耐受性和免疫抑制性肿瘤微环境等因素，其作为单一疗法的疗效仍然有限。将癌症疫苗与全身抗癌疗法（SACTs）相结合是一种有望提高疗效的策略。然而，与免疫检查点抑制剂（ICIs）和化疗联合以增强免疫原性的最佳时机和组合尚未完全明确。本综述旨在评估抗病毒和抗癌疫苗与SACTs（包括化疗和ICIs）联合使用时免疫原性的相关证据，特别关注疫苗接种相对于SACT的时间。此外，我们评估了类固醇对免疫原性的影响。我们的研究结果表明，疫苗接种时间至关重要，在化疗最低点（化疗后15天）接种疫苗时可观察到免疫反应增强。某些化疗药物，如低剂量节拍性环磷酰胺和紫杉醇，显示出免疫调节潜力，与疫苗联合使用时可增强T细胞反应。相反，类固醇可能会降低免疫原性。ICIs与癌症疫苗联合使用显示出协同效应的证据，同时给药通常比序贯给药产生更好的效果。探索各种时间和顺序的前瞻性试验对于优化抗癌疫苗的疗效至关重要。
