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- W2915648202 abstract "The FDA has begun to expand the approved uses of immune checkpoint blockade antibodies targeting CTLA-4 and PD-1. Blocking either checkpoint relieves the negative regulation of T-cells resulting in significant responses in patients with cancer. Data has now begun to emerge regarding differences between these two therapies. While αPD-1 therapy has a greater response rate (~30% vs. 11%) according to RECIST criteria, recent reports have suggested responses to αPD-1 may not be as durable as αCTLA-4. 25% of patients who initially responded to αPD-1 have tumor relapse within 24 months. In contrast, the 3-year survival rate of patients treated with αCTLA-4 is at least ~25% suggesting a durable response. Previous studies in bacterial or chronic LCMV infectious models have shown that αCTLA-4 can increase CD8+ memory T-cell formation, whereas genetic ablation of PD-1 on T-cells often promotes the terminally differentiated exhausted CD8+ T-cell phenotype, while attenuating memory T-cell formation. However, the mechanism which leads to relapse following αPD-1 treatment in tumor models is not clear. The goal of this project is to understand how immunotherapies shape memory T-cell formation and how that relates to the mechanism of tumor relapse. To test whether αCTLA-4 or αPD-1 can induce a better memory T-cell response, mice were vaccinated with irradiated B16F10 murine melanoma cells and treated αCTLA-4 or αPD-1. Mice were re-challenged with B16F10 80 days after vaccination. Although both αCTLA-4 and αPD-1 improved tumor rejection compared with controls, αCTLA-4 treated mice exhibited superior tumor control compared to αPD-1 (p 0.5). To test whether the frequency of memory T-cells recruited to the re-challenged tumor could affect memory T-cell response, antigen-specific pmel-1 T-cells were infused to mice following vaccination with αCTLA-4 or αPD-1. Our result suggested that there were more tumor-infiltrating pmel-1 T-cells in the αCTLA-4 treated group compared to the αPD-1 treated group (p 0.05) during re-challenge, indicating that the effect of the combined treatment is dominated by αCTLA-4. Collectively, our studies facilitate the design of combination immunotherapy treatments that enhance both response rates and generation of memory T-cells to prevent relapse. Citation Format: Stephen Mok, Colm R. Duffy, James P. Allison. Effects of anti-ctla-4 and anti-pd-1 on memory T-cell differentiation and resistance to tumor relapse [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1685. doi:10.1158/1538-7445.AM2017-1685" @default.
- W2915648202 created "2019-03-02" @default.
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- W2915648202 date "2017-07-01" @default.
- W2915648202 modified "2023-09-27" @default.
- W2915648202 title "Abstract 1685: Effects of anti-ctla-4 and anti-pd-1 on memory T-cell differentiation and resistance to tumor relapse" @default.
- W2915648202 doi "https://doi.org/10.1158/1538-7445.am2017-1685" @default.
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