Three Targets, One CAR T Therapy

First-in-human study demonstrates the potential of rapidly manufactured trispecific CAR T cells to deliver durable remissions in B-cell lymphoma

October 19, 2026
4 min

The Medicine Maker

Overview

A first-in-human phase I study evaluated point-of-care manufactured CAR T cells targeting CD19, CD20, and CD22 in patients with relapsed or refractory B-cell malignancies. Of 18 enrolled patients, 16 received treatment. The overall response rate was 50%, and the complete response rate was 38%. Grade 1–2 cytokine release syndrome occurred in 25%; no severe CRS, dose-limiting toxicities, or ICANS were reported.

Background

CD19-directed CAR T-cell therapies are used to treat some blood cancers, but relapse associated with loss or downregulation of target antigens remains a challenge. The investigational CAR T-cell product targets CD19, CD20, and CD22 and includes an OX40 costimulatory domain. The study evaluated point-of-care manufacturing using an automated platform at the treating institution. A 2018 ASCO-SITC meeting abstract also addressed trivalent CAR T cells in CD19-negative relapsed B-cell acute lymphoblastic leukemia.

Data Highlights

Measure	Study result
Trial enrollment	18 enrolled; 16 treated
Prior treatment	Median of 3 regimens
Manufacturing	Median 7 days (range, 6–10); successful for 16 of 17 patients
Overall response rate	50% of treated patients
Complete response rate	38% overall
B-cell non-Hodgkin lymphoma	5 of 6 patients (83%) achieved complete remission; 4 remained in remission beyond 1 year
B-cell acute lymphoblastic leukemia	Complete response rate of 25%
Chronic lymphocytic or prolymphocytic leukemia	Stable disease
Richter transformation	Neither of 2 patients responded
One-year overall survival	Approximately 61%
Safety	Grade 1–2 CRS in 25%; no severe CRS, dose-limiting toxicities, or ICANS reported

Key Findings

The phase I trial enrolled 18 patients with relapsed or refractory B-cell malignancies; 16 received the trispecific CAR T-cell product.
Point-of-care manufacturing using the CliniMACS Prodigy platform had a median duration of 7 days, and manufacturing succeeded for 16 of 17 patients for whom production was attempted.
Across treated patients, the overall response rate was 50% and the complete response rate was 38%; responses differed by disease type.
Five of six patients with B-cell non-Hodgkin lymphoma achieved complete remission, and four of those five remained in remission beyond one year.
Grade 1–2 CRS occurred in 25% of patients; the study reported no severe CRS, dose-limiting toxicities, or ICANS.
Pretreatment T cells from patients whose disease progressed showed increased expression of exhaustion-associated markers PD-1, TIM-3, and TOX. CAR T-cell expansion was not significantly associated with dose or clinical response.

Clinical Implications

The study reports early clinical and manufacturing results in a small, heterogeneous patient population. The researchers state that larger studies are needed to validate clinical benefits and that T-cell exhaustion warrants further investigation.

Conclusion

In this first-in-human phase I study, 16 patients with relapsed or refractory B-cell malignancies received point-of-care manufactured trispecific CAR T cells. The overall response rate was 50%, and the complete response rate was 38%; grade 1–2 CRS occurred in 25%, with no severe CRS or ICANS reported. The researchers state that larger studies are needed to validate clinical benefits.