Dimitrios Mathios, Maria Adelita Vizcaino Villalobos, Xiaobu Ye, Patrick M Forde, Jon Weingart, Kaisorn Chaichana, Matthias Holdhoff, Drew M Pardoll, Henry Brem, and Michael Lim
The antitumor activity of TIM-3 blocking antibodies has been investigated in preclinical models of cancer with promising results so far. Here we report in detail the first clinical experience with a human TIM-3 blocking antibody against high grade astrocytomas. Among a cohort of four brain tumor patients studied, three were treated with TIM-3 blocking antibody alone and one was treated with a combination of TIM-3 and PD-1 blocking antibodies. All patients had radiographic progression with progression free survival between 3-6.5 months. Three patients had transient grade 3 neurological toxicity. Three patients required dose reduction of TIM-3 due to symptomatic treatment-related edema. All patients had low percentage of TIM-3 positive immune cells and variable expression of PD-1, PD-L1, LAG-3 in the tumor microenvironment before treatment initiation. One of the four patients developed significant tumor edema on imaging during treatment that decreased significantly with administration of steroids. Histological examination of the tumor obtained before anti-TIM-3 initiation as well as after treatment showed significant tumor immune infiltration, compared to other tumors in this cohort. Overall, while there was no measurable clinical benefit among patients with progressive astrocytomas that were treated with TIM-3 blocking antibody in this pilot cohort, anti-TIM-3 may alter the tumor microenvironment.
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