Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapieSep 7, 2024

Astragalus polysaccharide boosts cancer-killing effects of CAR T cells by increasing a specific type of memory T cells

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 2, 2026

Abstract

APS significantly improved the persistence of GPC3-targeted CAR-T cells in tumor models.

CD122CXCR3 memory T cells are associated with longevity and effective tumor suppression.
APS increased the population of memory T cells while reducing the PD-1 subset within CD8 CAR-T cells.
Increased expression of chemokines CXCL9 and CXCL10 by the tumor was observed with APS treatment.
APS enhanced the proliferation and migration of CAR-T cells in laboratory experiments.
Phosphorylation of STAT5 in CD8 CAR-T cells was promoted by APS, with inhibition of this activation reversing APS effects.

Simplified

Chimeric antigen receptor-engineered T (CAR-T) cell therapy of cancer has been a hotspot and promising. However, due to rapid exhaustion, CAR-T cells are less effective in solid tumors than in hematological ones. CD122CXCR3memory T cells are characterized with longevity, self-renewal and great antitumoral capacity. Thus, it's compelling to induce memory CAR-T cells to enhance their efficacy on solid tumors. Astragalus polysaccharide (APS) has reportedly exhibited antitumoral effects. However, it's unclear if APS has an impact on CD8memory T cell generation or persistence. Using two human cancer cell lines, here we found that APS significantly improved the persistence of GPC3-targeted CAR-T cells and enhanced their suppression of tumor growth in both Huh7 and HepG2 xenograft models of hepatocellular carcinoma. APS increased CD122/CXCR3memory T cells, but decreased their PD-1subset within CD8CAR-T cells in tumor-bearing mice, while these effects of APS were also confirmed with in vitro experiments. Moreover, APS augmented the expression of chemokines CXCL9/CXCL10 by the tumor in vivo and in vitro. It also enhanced the proliferation and chemotaxis/migration of CAR-T cells in vitro. Finally, APS promoted the phosphorylation of STAT5 in CD8CAR-T cells, whereas inhibition of STAT5 activation reversed these in vitro effects of APS. Therefore, APS enhanced the antitumoral effects of CD8CAR-T cells by promoting formation/persistence of CD122/CXCR3/PD-1memory T cells and their migration to the tumor. + + + + + + + + + + + -

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Astragalus polysaccharide boosts cancer-killing effects of CAR T cells by increasing a specific type of memory T cells

Abstract

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