Targeting CD19 with genetically modified EBV-specific human T lymphocytes.
Human Epstein-Barr virus-specific T cells were genetically modified to express chimeric receptors specific for human CD19, which is expressed on the cell surface of most B cell malignancies. The receptor-modified EBV-specific T cells can be expanded and maintained long term in the presence of EBV-infected B cells. They recognize autologous EBV-infected targets through their conventional T cell receptor, and allogeneic EBV-infected targets and tumor targets through their chimeric receptor. They efficiently lyse both EBV and CD19-positive tumor targets in the absence of background cytotoxicity against CD19-negative targets. Donor-derived EBV-specific T cells expressing chimeric anti-tumor receptors may represent a source of effector cells that could be safely administered to leukemia patients to eradicate minimal residual disease after allogeneic bone marrow transplantation.
Roessig
C
C
University Children's Hospital Münster, Department of Pediatric Hematology and Oncology, Albert-Schweitzer-Str. 33, 48149 Münster, Germany.
Scherer
S P
SP
Baer
A
A
Vormoor
J
J
Rooney
C M
CM
Brenner
M K
MK
Juergens
H
H
D018941:Antigens, CD19 / Q000235:genetics*; D015870:Gene Expression; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007128:Immunoglobulin Fragments / Q000235:genetics; D007074:Immunoglobulin G / Q000235:genetics; D016219:Immunotherapy, Adoptive; D007938:Leukemia / Q000628:therapy; D018365:Neoplasm, Residual / Q000628:therapy; D011961:Receptors, Fc / Q000235:genetics; D011993:Recombinant Fusion Proteins; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000378:metabolism*; D014162:Transfection
D018941:Antigens, CD19; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; C055966:immunoglobulin Fv