Immunotherapy for Renal Cell Carcinoma-What More is to Come?

The treatment of renal cell carcinoma (RCC), a malignancy that is typically chemoresistant, has drastically evolved with the introduction of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) and immune checkpoint inhibitors (ICIs). The introduction of ICI-based regimens has significantly improved outcomes for patients with metastatic RCC. Currently, first-line therapy for patients with metastatic RCC involves multiple ICI-based regimens, either dual ICIs (with anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA- 4) and anti-programmed cell death- 1 (PD- 1) therapies) or anti-PD- 1 therapy in combination with VEGFR TKIs. Despite improving patient outcomes with ICI-based regimens, durable responses remain uncommon, highlighting the need for innovative treatment strategies. In this review, we highlight the current standard of care ICI-based regimens followed by ongoing clinical trials with novel combinations of existing FDA-approved agents and targets. We also discuss novel immunotherapies currently in clinical trials, which aim to improve antitumor T cell immunity either by improving T cell activation or T cell navigation to the tumor microenvironment. The incorporation of these novel therapies offers the potential to improve RCC patient outcomes, particularly by enhancing the durability of treatment responses.