Impact of systemic anticancer therapy timing on cancer vaccine immunogenicity: a review.

Abstract

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.