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Targeting CD19 with genetically modified EBV-specific human T lymphocytes
C Roessig1, S P Scherer, A Baer
1University Children's Hospital Münster, Department of Pediatric Hematology and Oncology, Albert-Schweitzer-Str. 33, 48149 Münster, Germany.
Annals of Hematology
|March 4, 2003
Summary
Genetically engineered Epstein-Barr virus-specific T cells target CD19-expressing B cell malignancies. These modified T cells show potential for eradicating minimal residual disease in leukemia patients post-transplant.
Area of Science:
- Immunology
- Oncology
- Cell Therapy
Background:
- Epstein-Barr virus (EBV) infects B cells, contributing to certain malignancies.
- CD19 is a cell surface marker present on most B cell malignancies.
- Allogeneic bone marrow transplantation is a treatment for leukemia, but minimal residual disease can persist.
Purpose of the Study:
- To genetically modify human EBV-specific T cells to express chimeric receptors targeting CD19.
- To evaluate the efficacy and safety of these modified T cells in targeting EBV and CD19-positive tumor cells.
- To assess their potential as an adoptive immunotherapy for leukemia patients.
Main Methods:
- Genetic modification of human EBV-specific T cells to express chimeric antigen receptors (CARs) targeting CD19.
- Expansion and maintenance of modified T cells in the presence of EBV-infected B cells.
- Assessment of T cell recognition of autologous and allogeneic targets via T cell receptor (TCR) and CAR.
- Evaluation of cytotoxic activity against CD19-positive tumor targets and EBV-infected cells.
Main Results:
- Receptor-modified EBV-specific T cells could be expanded and maintained long-term.
- These cells recognized autologous EBV-infected targets via TCR and allogeneic targets via CAR.
- Efficient lysis of both EBV and CD19-positive tumor targets was observed.
- No significant background cytotoxicity against CD19-negative targets was detected.
Conclusions:
- Donor-derived EBV-specific T cells engineered with chimeric anti-CD19 receptors are effective against B cell malignancies.
- These cells demonstrate specific tumor cell lysis without off-target effects.
- This approach offers a potential source of effector cells for eradicating minimal residual disease in leukemia patients after allogeneic bone marrow transplantation.