IMMUNOLOGY2026™ Conference Recordings For Attendees-CAR-T with ICOS costimulation lacks therapeutic efficacy in patients due to strong trogocytosis and failure of expansion

CAR-T with ICOS costimulation lacks therapeutic efficacy in patients due to strong trogocytosis and failure of expansion

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Video Summary

The speaker presented preclinical and early clinical data on trispecific CAR T-cells using ICOS signaling. While CAR T therapy is effective, relapse and toxicity can occur due to antigen escape, trogocytosis, and T-cell exhaustion. A prior phase 1 trial of dual-target CD19/CD20 4-1BB CAR T-cells showed strong patient responses. However, the ICOS-based trispecific CAR T-cells, designed to target CD19, CD20, and CD22, failed to expand in four lymphoma patients and showed no IL-6-linked expansion. In mouse and cell-culture models, ICOS CAR T-cells had poorer survival, weak expansion, higher exhaustion markers, and sustained CAR internalization. They also acquired more CD19 on their surface, consistent with trogocytosis, which likely triggered fratricide and cell death. The conclusion was that ICOS as a single co-stimulatory domain may drive strong trogocytosis and limit CAR T persistence, suggesting caution in future CAR design.

Meta Tag

Date April 16, 2026 9:00 AM - 9:15 AM

Room 157

Session T Cells in Cancer II

Speaker Yongxia Wu

Track Tumor Immunology: Cellular Responses and Tumor Microenvironment (TIME)

Year 2026

Keywords

trispecific CAR T-cells

ICOS signaling

trogocytosis

T-cell exhaustion

lymphoma therapy

April 16, 2026 9:00 AM - 9:15 AM

157

T Cells in Cancer II

Yongxia Wu

Tumor Immunology: Cellular Responses and Tumor Microenvironment (TIME)

2026