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Updated: Sep 14, 2025

Manufacturing Chimeric Antigen Receptor CAR T Cells for Adoptive Immunotherapy

Manufacturing Chimeric Antigen Receptor CAR T Cells for Adoptive Immunotherapy

Published on: December 17, 2019

Chimeric antigen receptor T-cell therapy for high-grade B-cell lymphoma NOS.

Nasheed M Hossain¹, Kwang Woo Ahn², Jinalben Patel³

¹Division of Hematology/Oncology-Cell Therapy and Transplant Program, University of Pennsylvania-Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

British Journal of Haematology

|July 22, 2025

Summary

Chimeric antigen receptor T-cell (CAR-T) therapy shows limited efficacy in high-grade B-cell lymphoma (HGBCL-NOS), with lower survival rates compared to other large B-cell lymphomas. Further research is needed to improve outcomes for this challenging patient group.

Keywords:

chimeric antigen receptor T cell therapy lymphomas non‐Hodgkin lymphoma

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Published on: November 12, 2019

Area of Science:

Hematology
Oncology
Immunotherapy

Background:

Chimeric antigen receptor T-cell (CAR-T) therapy is a standard treatment for large B-cell lymphoma (LBCL).
Clinical trials often exclude patients with high-grade B-cell lymphoma, not otherwise specified (HGBCL-NOS), leaving their treatment outcomes unclear.

Purpose of the Study:

To evaluate the efficacy and safety of CD19 CAR-T therapy in patients with HGBCL-NOS.
To compare outcomes in HGBCL-NOS patients receiving CAR-T therapy with those reported for other LBCL histologies.

Main Methods:

Analysis of 111 HGBCL-NOS patients who received CAR-T therapy from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry.
Assessment of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) rates and severity.
Evaluation of overall survival (OS), progression-free survival (PFS), non-relapse mortality, and relapse/progression rates at 2 years post-infusion.

Main Results:

The incidence of CRS was 74% (7.7% grade 3+) and ICANS was 45.2% (22.6% grade 3+).
Two-year OS and PFS probabilities were 41.6% and 28.7%, respectively.
Two-year non-relapse mortality was 3.1%, while relapse/progression occurred in 68.1% of patients, indicating less favorable outcomes compared to other LBCLs.

Conclusions:

HGBCL-NOS patients represent a challenging group for CAR-T therapy, with lower response rates and survival compared to other LBCLs.
While approximately one-third of patients achieved a durable response, overall outcomes suggest CAR-T therapy may be less effective in HGBCL-NOS.
Further strategies are needed to improve CAR-T therapy effectiveness in this specific lymphoma subtype.