T cell receptor transduced into primary human lymphocytes

08-22-2006

Recent research from the United States has chronicled the transduction of an HLA-DP4-restricted NY-ESO-1-specific T cell receptor (TCR) into primary human CD4+ lymphocytes.

"CDNAs encoding functional TCR alpha and beta chains from a CD4+ T cell line (SG6) generated by repeated stimulation of a melanoma patient's peripheral blood mononuclear cells with HLA-DP4-restricted, NY-ESO-1-specific peptide p161-180 were cloned using a 5'rapid amplification of cDNA end method," wrote Y.B. Zhao and colleagues, National Cancer Institute.

"Three different TCR alpha chains and 7 TCR beta chains were found among the 84 alpha and 162 beta cDNA clones tested. By screening different combination of the alpha/beta chains using RNA electroporation, TRAV9-1 (V alpha 22.1) and TRBV20-1 (V beta 2) were found to be the functional pair in line SG6.

"Antibody blocking experiments confirmed that the specificity of TRAV9-1/TRBV20-1 mRNA-transfected T cells were CD4 dependent and HLA-DP4 restricted. A retroviral vector expressing both TRAV9-1 and TRBV20-1 was constructed and used for transduction of OKT3-stimulated peripheral blood lymphocytes from melanoma patients. TCR-transduced CD4 T cells were capable of recognizing peptide-pulsed antigen-presenting cells (Epstein-Barr virus transformed B-cells, dendritic cells, and peripheral blood mononuclear cells), and protein-pulsed dendritic cells," reported the authors.

"Transduced cells were also capable of proliferation upon peptide stimulation and recognized peptide concentrations that were recognized by the parental line (0.2 mcM). In contrast to SG6, which could not recognize human tumors, TCR-transduced CD4 T cells could specifically recognize NY-ESO-1/HLA-DP4-expressing melanoma cells," the scientists wrote.

They concluded, "Major histocompatibility complex class II TCR-transduced CD4 T cells provides an alternative source of tumor antigen-specific T cells for adoptive immunotherapy of cancer patients."

Zhao and colleagues published their study in the Journal of Immunotherapy (Transduction of an HLA-DP4-restricted NY-ESO-1-specific TCR into primary human CD4+ lymphocytes. J Immunother, 2006;29(4):398-406).

For additional information, contact R.A. Morgan, Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.

Publisher contact information for the Journal of Immunotherapy is: Lippincott Williams & Wilkins, 530 Walnut St., Philadelphia, PA 19106-3621, USA.

Keywords: Bethesda, Maryland, United States, Biological Therapy, Epstein-Barr Virus, Gene Therapy, Major Histocompatibility Complex, Retroviral Vectors, HLA-DP4, Lymphocyte, Peptide.

This article was prepared by Cancer Gene Therapy Week editors from staff and other reports. Copyright 2006, Cancer Gene Therapy Week via NewsRx.com.