Published in:
Open Access 01-12-2020 | Original Article
The biologically functional identification of a novel TIM3-binding peptide P26 in vitro and in vivo
Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2020
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Purpose
Recent studies have shown that TIM3 plays an important role in T-cell failure, which is closely related to the resistance to anti-programmed cell death protein 1 (PD-1) treatment. However, there have been no reports on the application of peptide blockers to TIM3. In this study, we endeavored to identify the in vitro and in vivo anti-tumor activities of a TIM3-targeting peptide screened from the phage peptide library.
Methods
Phage display peptide library technology, surface plasmon resonance, flow cytometry, and mixed lymphocyte reaction were utilized to screen and demonstrate the bioactivities of P26, a TIM3-targeting peptide. Meanwhile, tumor growth assay was performed to evaluate the anti-tumor effect of P26.
Results
In terms of affinity, we demonstrated that P26 specifically binds to TIM3 at the cellular and molecular levels, which therefore blocks the interaction between TIM3 and Galectin-9 (Gal-9) and competes with Gal-9 to bind TIM3. Additionally, P26 significantly increases T-cell activity and elevates IFN-γ and IL-2 levels in a dose-dependent manner. Notably, P26 also counteracts Gal-9-mediated T-cell suppression. More importantly, P26 can inhibit growth of MC38-hPD-L1 tumor in mice.
Conclusions
P26, as a novel TIM3-binding peptide, has the ideal bioactivity connecting to TIM3 and the potential prospect of application in immunotherapy as an alternative or adjuvant to existing agents.