Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 199, Issue 7, Pages 885-894Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20031110
Keywords
T cell receptor; gene transfer; minor histocompatibility antigen; virus-specific T cells; leukemia reactive
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T cells directed against tumor histocompatibility antigens (mHags) might be responsible for eradication of hematological malignancies after allogeneic stem cell transplantation. We investigated whether transfer of T cell receptors (TCRs) directed against mHags, exclusively expressed on hematopoietic cells, could redirect virus-specific T cells toward antileukemic reactivity, without the loss of their original specificity. Generation of T cells with dual specificity may lead to survival of these TCR-transferred T cells for prolonged periods of time in vivo due to transactivation of the endogenous TCR of the tumor-reactive T cells by the latent presence of viral antigens. Furthermore, TCR transfer into restricted T cell Populations, which are nonself reactive, will minimize the risk of autoimmunity. We demonstrate that cytomegalovirus (CMV)-specific T cells can be efficiently reprogrammed into leukemia-reactive T cells by transfer of TCRs directed against the mHag HA-2. HA-2-TCR-transferred CMV-specific T cells derived from human histocompatibility leukocyte antigen (HLA)-A2(+) or HLA-A2(-) individuals exerted potent antileukemic as well as CMV reactivity, without signs of anti-HLA-A2 alloreactivity. The dual specificity of these mHag-specific, CR-redirectecl virus-specific T cells opens new possibilities for the treatment of hematological malignancies of HLA-A2(+) HA-2-expressing patients transplanted with HLA-A2-matched or -mismatched donors.
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