A CDK4/6 inhibitor-armed oncolytic adenovirus reverses T cell exhaustion through the Rb-p65-CCL5 pathway and potentiates the antitumor activity of anti-PD-1 or CAR-T therapy in colorectal cancer

1

The engineered oncolytic adenovirus ADV-PTD4-D3 enhances tumor control and T cell memory in colorectal cancer models.
2

ADV-PTD4-D3 reverses CD8+ T cell exhaustion by modulating the Rb-p65-CCL5 signaling pathway, improving T cell recruitment.
3

This therapy shows potent antitumor activity in both murine and humanized xenograft models without significant off-target toxicity.
4

ADV-PTD4-D3 improves the efficacy of anti-PD-1 and CAR-T therapies by addressing barriers of T cell infiltration and exhaustion.
5

The study suggests that localized modulation of T cell exhaustion pathways via oncolytic viruses is a viable strategy for enhancing antitumor immunity.

Frontiers In Immunology

by Dan Zhou, Beibei Ran, Lingkai Kong, Yan Liu, Lingjun Xiao, Xiangmei Chen, Wencui Liu, Xiao Li, Jing Zhang, Jiahui Zhang, Hao Wu, Guang Zhang, Xiaosong Gu, Wenjie Zhang, Junhua Wu, Chunping Jiang
June 15, 2026

1