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

At a Glance

Category	Detail
Condition	Relapsed or refractory B-cell malignancies
Key Mechanisms	Investigational CAR T cells target CD19, CD20, and CD22 to address antigen loss or downregulation; the construct includes an OX40 costimulatory domain.
Target Population	Patients with relapsed or refractory B-cell malignancies; 18 enrolled and 16 treated in this phase I study.
Care Setting	First-in-human phase I clinical trial using point-of-care CAR T-cell manufacturing at an academic cancer center.

Key Highlights

The overall response rate was 50%, with complete responses in 38% of treated patients.
Among patients with B-cell non-Hodgkin lymphoma, five of six achieved complete remission; four remained in remission beyond one year.
Median manufacturing time was seven days (range, six to 10); cells were successfully manufactured for 16 of 17 patients.
Grade 1 or 2 cytokine release syndrome occurred in 25% of patients; no severe cases, dose-limiting toxicities, or immune effector cell-associated neurotoxicity syndrome were reported.
The small, heterogeneous phase I population limits definitive conclusions; the researchers state that larger studies are needed.

Guideline-Based Recommendations

Diagnosis

The study used high-dimensional spectral flow cytometry to assess T-cell exhaustion-associated markers, including PD-1, TIM-3, and TOX.

Management

The investigational therapy targets CD19, CD20, and CD22 and incorporates an OX40 costimulatory domain.
Point-of-care manufacturing used the CliniMACS Prodigy automated platform and a lentiviral vector.

Monitoring & Follow-up

The study assessed clinical response, survival, cytokine release syndrome, dose-limiting toxicities, and immune effector cell-associated neurotoxicity syndrome.
Pretreatment T cells from patients whose disease progressed showed increased expression of exhaustion-associated markers.

Risks

Grade 1 or 2 cytokine release syndrome occurred in 25% of treated patients; no severe cases were reported.
No dose-limiting toxicities or immune effector cell-associated neurotoxicity syndrome were reported.
One manufacturing failure occurred in a heavily pretreated patient.

Patient & Prescribing Data

The trial enrolled 18 patients with relapsed or refractory B-cell malignancies; 16 received treatment and had a median of three prior treatment regimens.

Across treated patients, the overall response rate was 50% and the complete response rate was 38%. The one-year overall survival rate was approximately 61%. Responses varied by disease type.

Clinical Best Practices

Interpret the reported response and safety findings in light of the phase I design and small, heterogeneous patient population.
The researchers report that larger studies are needed to validate clinical benefits.
Further investigation of T-cell exhaustion as a potential biomarker is proposed by the researchers.