Challenges and opportunities in the development of combination immunotherapy with OX40 agonists

Redmond, William L

doi:10.1080/14712598.2023.2249396

Expert Opinion on Biological Therapy

2023

DOI: 10.1080/14712598.2023.2249396

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Challenges and opportunities in the development of combination immunotherapy with OX40 agonists

William L Redmond

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2024

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Pharmacologic HIF stabilization activates costimulatory receptor expression to increase antitumor efficacy of adoptive T cell therapy

Walter Jackson III,

Yang,

Salman

et al. 2024

Sci. Adv.

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Adoptive cell transfer (ACT) is a therapeutic strategy to augment antitumor immunity. Here, we report that ex vivo treatment of mouse CD8 + T cells with dimethyloxalylglycine (DMOG), a stabilizer of hypoxia-inducible factors (HIFs), induced HIF binding to the genes encoding the costimulatory receptors CD81, GITR, OX40, and 4-1BB, leading to increased expression. DMOG treatment increased T cell killing of melanoma cells, which was further augmented by agonist antibodies targeting each costimulatory receptor. In tumor-bearing mice, ACT using T cells treated ex vivo with DMOG and agonist antibodies resulted in decreased tumor growth compared to ACT using control T cells and increased intratumoral markers of CD8 + T cells (CD7, CD8A, and CD8B1), natural killer cells (NCR1 and KLRK1), and cytolytic activity (perforin-1 and tumor necrosis factor–α). Costimulatory receptor gene expression was also induced when CD8 + T cells were treated with three highly selective HIF stabilizers that are currently in clinical use.

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Pharmacologic HIF stabilization activates costimulatory receptor expression to increase antitumor efficacy of adoptive T cell therapy

Walter Jackson III,

Yang,

Salman

et al. 2024

Sci. Adv.

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show abstract

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Challenges and opportunities in the development of combination immunotherapy with OX40 agonists

Cited by 1 publication

References 144 publications

Pharmacologic HIF stabilization activates costimulatory receptor expression to increase antitumor efficacy of adoptive T cell therapy

Pharmacologic HIF stabilization activates costimulatory receptor expression to increase antitumor efficacy of adoptive T cell therapy

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