Beyond LAG-3: Promising Immuno-Oncology Targets in Kidney Cancer

Katy Beckermann, MD, PhD, of Vanderbilt-Ingram Cancer Center, and Michael Atkins, MD, of Georgetown Lombardi Comprehensive Cancer Center, weigh the potential of targeting T regulatory cells (Tregs) in kidney cancer treatment, particularly in relation to PD-1 therapy.

Dr. Atkins highlights ongoing research into CTLA-4 antibodies that deplete Tregs and their potential to enhance response rates when combined with anti-PD-1 therapy.

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Dr. Beckermann: We have delved into LAG-3 quite extensively. Are there any other immuno-oncology targets that you find particularly promising for use in RCC?

Dr. Atkins: There is fascinating research led by Drs. Arlene Sharpe and Sabina Signoretti at Dana-Farber Cancer Institute. They have uncovered that when PD-1 is present on Tregs and anti-PD-1 therapy is administered, it actually enhances the immunosuppressive function of Tregs.

The responsiveness of tumors to anti-PD-1 immunotherapy might hinge on the balance of PD-1 expression between effector T cells and Tregs. Thus, interventions aimed at disrupting this balance, such as targeting Tregs, could be pivotal.

Exploring CTLA-4 antibodies with Treg-depleting properties or other agents capable of reducing Treg populations could represent a promising avenue for advancing immunotherapy.

In the ARCHITECT trial, we are investigating the CTLA-4 antibody botensilimab, known for its Treg-depleting effects. Preliminary findings in MSS colon cancer suggest activity when combined with anti-PD-1, surpassing the efficacy of nivo/ipi. We are eager to assess its potential in kidney cancer and evaluate its impact on treatment response compared to nivo/ipi, particularly concerning specific biomarkers.

Dr. Beckermann: I am eagerly awaiting the results of the ARCHITECT trial. Swift enrollment and robust data would undoubtedly benefit our patients immensely.

View their previous comments on Redefining Immune Strategies: LAG-3 With PD-1 in Kidney Cancer and The Potential Synergistic Power of LAG-3 and PD-1 in Kidney Cancer.