Work

Reviving cancer vaccines in renal cell carcinoma: a new chapter in immunotherapy for kidney cancer

Year: 2026

Type: review

Abstract: Renal cell carcinoma (RCC) remains one of the most immunologically responsive solid tumors, yet durable benefit from immune checkpoint inhibitors (ICIs) is achieved in only a subset of patients. Although ICIs are conventionally thought to primarily act by reinvigoration and expanding preexisting antitumor T-cell responses, their ability to consistently broaden tumor-specific immunity remains limited, highlighting a potential role for therapeutic cancer vaccines in RCC to expand, activate, and diversify tumor-targeting T-cell populations. Vaccine strategies in RCC have evolved from broad autologous whole tumor antigen (WTA) approaches to defined tumor-associated antigen (TAA) platforms and, more recently, personalized neoantigen vaccines enabled by next-generation sequencing. Early WTA vaccines demonstrated feasibility and immunogenicity, particularly in the adjuvant setting, but failed to consistently improve survival in metastatic disease. TAA-directed vaccines targeting Wilms' tumor 1, survivin, mucin 1, carbonic anhydrase IX, and 5T4 confirmed on-target immune activation but yielded limited clinical benefit. Personalized neoantigen vaccines, particularly in high-risk resected clear cell RCC, have shown robust and durable T-cell responses with encouraging early clinical signals and are being investigated in larger clinical trials. However, vaccine efficacy in RCC is constrained by tumor-intrinsic immune suppression, heterogeneous antigen presentation, and subtype-specific tumor immune microenvironments. Emerging strategies to further modulate immunosuppressive signals from tumor cells and the microenvironment may enhance vaccine responsiveness, particularly in immune-cold subtypes. Future progress will require stage-specific application, improved antigen selection, and rational combinatorial approaches tailored to RCC biology.

Source: Immuno-Oncology Technology

DOI: 10.1016/j.iotech.2026.101611

Authors: F.M. Scallo, J.J. Ishizuka, D.A. Braun

Institutions: Yale Cancer Center, Yale University

Language: English

Topic: Immunotherapy and Immune Responses

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,340