Fig. 8: Schematic of hypothesized working model.

Due to tumor targeting, TIM3-ProIL2V2 bound to TIM3⁺ TILs and enhanced the specificity of ProIL2V2 delivery to tumor-specific T cells while minimizing systemic toxicity. After MMPs digestion inside TME, the released IL-2 from TIM3-ProIL2V2 promoted the activation of not only TIM3⁺ exhausted T cells but also proliferation and differentiation of rest TIM3⁻ T cells, including PD1⁺TIM3⁻ effector CD8⁺ T cells and stem-like CD8⁺ T cells. Released IL2V2 thus, enhances the responses across a broader spectrum of TIL subsets from progenitor, early, and late stages of effector cells, boosted stronger antitumor immune responses.