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Hydroxychloroquine + aldesleukin is a combination therapy investigated for the treatment of metastatic renal cell carcinoma (mRCC). This specific regimen was the subject of a Phase I/II clinical trial led by Dr. Leonard J. Appleman and the Cytokine Working Group (CWG). The combination pairs hydroxychloroquine, an FDA-approved antimalarial and autophagy inhibitor, with high-dose aldesleukin (recombinant interleukin-2). The therapeutic rationale is based on the hypothesis that inhibiting autophagy—a cellular degradation process that can promote tumor survival and immune evasion—using hydroxychloroquine could enhance the anti-tumor efficacy of IL-2-mediated immunotherapy. In the trial, hydroxychloroquine was administered orally to prevent lysosomal acidification, while aldesleukin was given as an intravenous bolus to stimulate T-cell and natural killer cell activity.
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