Abstract 2733: NB202: A bispecific anti-PD1/TIM-3 antibody for cancer immunotherapy

Abstract Despite the remarkable efficacy of PD-(L)1 therapy, a significant proportion of cancer patients fail to respond or develop resistance over time. Co-expression of T-cell immunoglobulin and mucin domain containing-3 (TIM-3) with PD-1 on primed T cells has been observed in patients exhibiting resistance to PD-1 blockade. Moreover, TIM-3 is also expressed on other immune cells, including NK and DC, and plays a negative regulatory role in these immune cells. Therefore, the dual blockade of PD-1 and TIM-3 holds potential for enhanced clinical benefits. NB202 is a bispecific anti-PD1/TIM-3 antibody that has been designed to optimize the therapeutic response of anti-PD1 therapy by maximizing TIM-3 blockade on antigen-experienced T cells, enhancing NK cell activity, and improving antigen presentation ability of antigen-presenting cells (APC). NB202 has demonstrated high affinity binding to human TIM3 and PD-1 in the low nanomolar range. Moreover, it can simultaneously bind to TIM-3 and PD-1 receptors through a trans-manner, suggesting its potent capacity to enhance the interaction between T cells and dendritic cells (DCs). In classic MLR (mixed lymphocyte reaction) and T cell stimulation assays, NB202 has exhibited superior efficacy compared to the combination of anti-PD1 mAb and anti-TIM3 monoclonal antibodies as it significantly enhances the secretion level of interferon-gamma (IFN-gamma), and particularly interleukin-2 (IL-2). Moreover, in an anti-PD1 resistant mouse model, NB202 has shown promising efficacy results. Citation Format: Jinyu Dong, Yu Zhang, Binbin Wang, Dong Wang, Tingting Bu, Jie Ni, Bishnu Nayak, Xin Dong. NB202: A bispecific anti-PD1/TIM-3 antibody for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2733.