(Teva Pharmaceuticals) Preclinical in vivo characterization of the anti-tumor activity of a non-blocking PD-1 antibody fused to attenuated IL-2

Abstract

• TEV-56278 is a fusion protein developed by Teva, combining a non-blocking anti-PD1 antibody with an attenuated IL-2 variant. This design targets IL-2 to PD-1+ T cells, aiming to enhance anti-tumor immunity while minimizing systemic IL-2 side effects.
• IL-2 is crucial for immune regulation, as it enhances T cell proliferation and activation, thereby boosting anti-tumor immunity. However, its clinical use is limited by systemic toxicity and a narrow therapeutic window (Atkins et al., 1999). TEV-56278 features an attenuated IL-2 moiety, developed to mitigate these risks.

• PD-1 expression is significantly higher in tumor-infiltrating T cells compared to circulating and other tissue-resident T cells (Ahmadzadeh et al., 2009). TEV-56278's design allows the IL-2 variant to target PD-1-expressing cells while preserving PD-1 receptor functionality. This enables treatment both as a monotherapy and in combination with an anti-PD1 antibody.
• Here, we describe the impact of TEV-56278 and its murine surrogate, mAnti-PD1-IL2, on tumor progression and tumor-infiltrating lymphocytes in pre-clinical tumor models.