Related Experiment Video
Updated: Dec 4, 2025
Measuring TCR-pMHC Binding In Situ using a FRET-based Microscopy Assay
Published on: October 30, 2015
The biologically functional identification of a novel TIM3-binding peptide P26 in vitro and in vivo
Tangwu Zhong1,2, Chuanke Zhao2, Shuntao Wang2
1School of Basic Medicine, Jiamusi University, 258 Xuefu Street, Jiamusi, 154007, Heilongjiang Province, China.
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.
Insights
A novel peptide, P26, targets TIM3 to enhance T-cell activity and combat tumor growth. This TIM3-targeting peptide shows promise as a new immunotherapy agent against cancer resistance.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- T-cell failure is linked to resistance against anti-programmed cell death protein 1 (PD-1) therapies.
- T-cell immunoglobulin and mucin-domain containing-3 (TIM3) is implicated in T-cell dysfunction.
- No peptide blockers targeting TIM3 have been previously reported.
Purpose of the Study:
- To identify and characterize the anti-tumor activities of a novel peptide targeting TIM3.
- To evaluate the in vitro and in vivo efficacy of a phage-displayed peptide, P26, as a TIM3 inhibitor.
Main Methods:
- Phage display peptide library technology was used to screen for TIM3-targeting peptides.
- Surface plasmon resonance, flow cytometry, and mixed lymphocyte reaction assays assessed P26 bioactivity.
- In vivo tumor growth assays were conducted to evaluate the anti-tumor effect of P26.
Main Results:
- P26 specifically binds to TIM3 at cellular and molecular levels, blocking TIM3-Galectin-9 (Gal-9) interaction.
- P26 enhances T-cell activity, increasing IFN-γ and IL-2 levels, and counteracts Gal-9-mediated suppression.
- P26 demonstrated significant inhibition of MC38-hPD-L1 tumor growth in mice.
Conclusions:
- P26 is a novel peptide with potent TIM3-binding capabilities.
- P26 exhibits significant anti-tumor activity in vitro and in vivo.
- P26 holds potential as an alternative or adjuvant therapeutic in cancer immunotherapy.
