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Review
. 2023 Apr 6;28(4):297-308.
doi: 10.1093/oncolo/oyac263.

Antibody-Based Therapeutics for the Treatment of Renal Cell Carcinoma: Challenges and Opportunities

Ahmed M Mahmoud  1 , Reza Nabavizadeh  1 , Rodrigo Rodrigues Pessoa  1 , Ishita Garg  2 , Jacob Orme  3 , Brian A Costello  1   3 , John Cheville  4 , Fabrice Lucien  1
Affiliations
Review

Antibody-Based Therapeutics for the Treatment of Renal Cell Carcinoma: Challenges and Opportunities

Ahmed M Mahmoud et al. Oncologist. .

Abstract

Renal cell carcinoma (RCC) is among the top 10 most common cancers in both men and women with an estimated 75 000 cases each year in the US. Over the last decade, the therapeutic landscape for patients with metastatic RCC has significantly evolved, with immunotherapy emerging as the new front-line therapy. Despite significant improvement in toxicity profile and survival outcomes, key concerns such as patient selection, treatment sequencing, and intrinsic and acquired resistance remain unresolved. Emerging options such as antibody-based therapeutics (eg, anti-CD70, anti-CA9, and anti-ENPP3) are being explored in clinical trials for patients with cancer resistant or refractory to current immunotherapies. Despite positive results for hematological cancers, breast cancer, and more recently bladder cancer, most antibody-based therapies failed to improve the outcomes in patients with advanced RCC. This underscores the need to understand the underlying causes of failed responses to this treatment class, which will ultimately support the rational design of more effective and tolerable treatments. In this review, we summarize the evolving landscape of RCC therapeutics and describe recent clinical trials with emerging antibody-based therapeutics. We also describe the challenges that need to be overcome for the successful creation of therapeutic antibodies for treating RCC.

Keywords: antibody-based therapies; clinical trials; emerging drugs; immunotherapy; metastatic RCC; renal cell carcinoma.

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Conflict of interest statement

The authors indicated no financial relationships.

Figures

Figure 1.
Figure 1.
Forest plots showing the association of investigational therapies with risk of mortality and progression-free survival in advanced RCC.
Figure 2.
Figure 2.
Recent clinical trials evaluating new antibody-based therapeutics in the treatment of RCC. Abbreviations: CA9, carbonic anhydrase 9; CAR-T, chimeric antigen receptor T cells; TIM-1, T cell immunoglobulin mucin-1; ADC, antibody-drug conjugate; ENPP3, ectonucleotide pyrophosphatase/phosphodiesterase 3; PFS, progressive-free survival; OS, overall survival.
Figure 3.
Figure 3.
Challenges and opportunities with antibody-based therapeutics.
See this image and copyright information in PMC

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