Phosphoantigens(pAgs) are small organophosphorus compounds with nanomolar potential to activate human γδ T cells. The compounds bind to the intracellular domain of the butyrophilin(BTN) 3A1 protein in target cells and modify the complex of BTN3A1/2A1, which is detected by γδ T cells. An obstacle to the clinical development of pAgs is the lack of cancer cell specificity in the expression pattern of BTN3A1, which is expressed in both normal and malignant cells. To overcome this obstacle, we investigated various approaches to modify the compound structure and synthetic routes to enable conjugation that can promote tumor delivery and trigger an anticancer γδ T cell response. The synthesized compounds were tested in cellular assays of γδ T cell stimulation and for stability in human plasma.

Synthesis and evaluation of conjugatable phosphoantigens

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ACS Fall 2022

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