What question did this study set out to answer?

To evaluate whether a novel bifunctional molecule combining the tumor-penetrating peptide iRGD with an anti-CD3 antibody can improve T-cell infiltration and activation in solid tumors.

May 1, 2021Journal for ImmunoTherapy of CancerOpen Access

Bifunctional iRGD-anti-CD3 enhances antitumor potency of T cells by facilitating tumor infiltration and T-cell activation

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To evaluate whether a novel bifunctional molecule combining the tumor-penetrating peptide iRGD with an anti-CD3 antibody can improve T-cell infiltration and activation in solid tumors.
Generated a bifunctional iRGD-anti-CD3 agent designed to immobilize iRGD onto T-cell surfaces via CD3 binding.
Assessed T-cell infiltration and activation using 3D tumor spheroids, confocal microscopy, flow cytometry, and transmission electron microscopy.
Evaluated in vivo antitumor efficacy, survival, and synergy with programmed cell death protein 1 (PD-1) blockade in multiple xenograft mouse models using histology, real-time fluorescence, and bioluminescence imaging.
iRGD-anti-CD3 modification facilitated T-cell penetration into 3D spheroids and xenografts while triggering T-cell activation and direct tumor cell cytotoxicity.
Modified T cells significantly suppressed tumor growth and prolonged survival in xenograft models, with therapeutic efficacy further augmented by PD-1 blockade.
Mechanistic evaluations showed that iRGD-anti-CD3 promoted T-cell extravasation through vesiculovacuolar organelle transport pathways within endothelial cytoplasm.

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Implication

Preclinical study demonstrates enhanced tumor penetration and activation of T cells using bifunctional iRGD-anti-CD3 in mice, indicating improved adoptive cell therapy efficacy.

Cite This Study

Zhou et al. (2021) studied this question.

synapsesocial.com/papers/6a7387db7af34f94aaa72f0a https://doi.org/10.1136/jitc-2020-001925

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Implication

Preclinical study demonstrates enhanced tumor penetration and activation of T cells using bifunctional iRGD-anti-CD3 in mice, indicating improved adoptive cell therapy efficacy.

Bifunctional iRGD-anti-CD3 enhances antitumor potency of T cells by facilitating tumor infiltration and T-cell activation

Key Points

Discussion

Implication

Cite This Study

Bifunctional iRGD-anti-CD3 enhances antitumor potency of T cells by facilitating tumor infiltration and T-cell activation

Key Points

Discussion

Implication

Cite This Study

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