What question did this study set out to answer?

The research aims to investigate the relationship between OX40 agonist affinity and its effectiveness in cancer immunotherapy, focusing on T cell modulation.

April 1, 2026Journal for ImmunoTherapy of CancerOpen Access

HFB301001, an OX40-based immunotherapy, drives Treg clearance and CTL activation through optimized OX40 receptor clustering

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Authors

JZJiliang ZhaoShenzhen University DZDongping ZhangNankai University YLYun-Yueh LuHiFiBiO Therapeutics (United States)

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Implication

Demonstrates enhanced T cell activation and regulatory T cell clearance with an optimized OX40 agonist in murine tumor models, suggesting its potential for cancer treatment.

Key Points

The research aims to investigate the relationship between OX40 agonist affinity and its effectiveness in cancer immunotherapy, focusing on T cell modulation.
Generated OX40 agonist antibodies with varying affinities via phage display.
Modeled antibody-receptor interactions using AI-based predictions and validated through hydrogen-deuterium exchange.
Assessed T cell activation and Treg depletion through confocal microscopy and reporter cell assays.
Evaluated anti-tumor efficacy in murine models and cellular response using various immune profiling techniques.
The low-affinity OX40 agonist HFB301001 exhibited stronger receptor clustering compared to high-affinity variants.
HFB301001 enhanced T cell activation and facilitated more effective Treg depletion in vitro.
HFB301001 led to increased intratumoral T cell infiltration and activation in vivo, showing it outperforms high-affinity variants.
Favorable safety profile observed in cynomolgus monkeys, indicating potential for human applications.

Cite This Study

Zhao et al. (2026) studied this question.

synapsesocial.com/papers/69ccb5d116edfba7beb87828 https://doi.org/10.1136/jitc-2025-014185

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Implication

Demonstrates enhanced T cell activation and regulatory T cell clearance with an optimized OX40 agonist in murine tumor models, suggesting its potential for cancer treatment.

HFB301001, an OX40-based immunotherapy, drives Treg clearance and CTL activation through optimized OX40 receptor clustering

Discussion

Member takes

Implication

Key Points

Cite This Study

HFB301001, an OX40-based immunotherapy, drives Treg clearance and CTL activation through optimized OX40 receptor clustering

Discussion

Member takes

Implication

Key Points

Cite This Study

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