Adoptive cellular immunotherapy with CD19-specific T cells.
BACKGROUND
No effective therapeutic modalities exist for the treatment of relapsed high risk acute lymphoblastic leukemia (ALL). Adoptive cellular immunotherapy by transfusion of polyclonal donor lymphocytes is not always effective and is limited by cellular cross-reactivity with normal tissues, leading to development of clinical graft-versus-host disease (GVHD).


METHODS
To develop an immunotherapeutic strategy for targeted elimination of residual leukemic blasts, human T cells were gene-modified to express CD19-specific chimeric receptors.


RESULTS
Gene-modified T cells specifically lyse CD19-expressing lymphatic blast cells, however, they show a limited proliferative response to stimulation with CD19. Integration of the signal transduction domain of the costimulatory molecule CD28 enhances the proliferative properties of the gene-modified T cells.


CONCLUSIONS
Adoptive transfer of gene-modified virus-specific T cells may provide a useful strategy for prevention and early treatment of ALL relapses following allogeneic stem cell transplantation.
Rössig
C
C
University Children's Hospital Münster, Department of Pediatric Hematology and Oncology, Münster. rossig@uni-muenster.de
Pscherer
S
S
Landmeier
S
S
Altvater
B
B
Jürgens
H
H
Vormoor
J
J
D018941:Antigens, CD19 / Q000276:immunology*; D002461:Cell Line, Transformed; D002648:Child; D003001:Cloning, Molecular; D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes / Q000276:immunology*; D018014:Gene Transfer Techniques; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation / Q000276:immunology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000628:therapy*; D019233:Retreatment; D013601:T-Lymphocytes / Q000276:immunology*; D014161:Transduction, Genetic
D018941:Antigens, CD19; D000939:Epitopes