Immunomodulatory Therapies for Renal Cell Carcinoma

(E-pub Ahead of Print)

Author(s): Min Liu, Huizi Wu, Dangang Shangguan, Yueping Jiang, Xiangping Li, Shao Liu, Boting Zhou, Tao Yin, Zhicheng Gong*.

Journal Name: Protein & Peptide Letters


Renal Cell Carcinoma (RCC) is the most common tumor originating from the kidneys. In comparison to other solid tumors, RCC is poorly sensitive to conventional therapeutic modalities. As such, metastatic RCC (mRCC) continues to be associated with high rates of morbidity and mortality. Targeted agents have shown remarkable progress in RCC management with improved patients’ outcomes, but rarely induce complete response and patients develop resistance to therapy eventually. However, it is well known that RCC represents one of the most immunogenic cancers and is able to evoke immune response naturally, thus prompted the emergence of several immunotherapeutic strategies in the management of RCC with variable degrees of success. Modulating the immune system with cytokines, vaccines, and T-cell modulating agents offer hope for the patients with RCC. High-dose Interleukin-2 (IL-2) still remains an appropriate first-line treatment for selected patients and is associated with durable complete remissions in a small fraction of treated patients. RCC vaccines have much less toxicity than other current therapeutic agents and remain an important area for further research, for example, Oncophage and Reniale, the two representative RCC vaccines, have shown significant benefits as an adjuvant treatment for RCC. Immune checkpoint inhibitors are evolving rapidly due to the increased understanding of the genetic and metabolic basis of tumors. In particular, Nivolumab is the most completely characterized antiprogrammed cell death 1 (anti-PD-1) agent in RCC and even has been shown to be efficacious as monotherapy with mRCC following a failed antiangiogenic therapy. This review critically summarizes the state of the art in RCC therapeutic regimen with immunomodulation agents. We will focus on the clinical data and ongoing clinical trials exploring the use of immunotherapy with different agents for RCC. In addition, different novel immunotherapeutic agents are being investigated for their combination therapy with other immune therapies or other modalities. Prospects (e.g., potential future immunological targets, combination regimens, appropriate sequencing) for immune therapies of RCC are also set forth in this review.

Keywords: Renal cell carcinoma, immunotherapy, cytokines, vaccine therapy, T-cell modulation.

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(E-pub Ahead of Print)
DOI: 10.2174/0929866525666180531080118
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