Activated dual specificity lymphocytes and their methods of use
AssigneeThe United States of America as represented by the Department of Health and Human Services
InventorsPatrick Hwu, Michael H. Kershaw, Steven A. Rosenberg
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Abstract
The present invention relates to preventive, therapeutic, and diagnostic compositions and methods employing lymphocytes having T-cell receptors and chimeric receptors. In particular, the invention relates to pre-selected dual-specificity lymphocytes having endogenous T-cell receptors and chimeric T-cell receptors that recognize a strong antigen and tumor associated antigens where the pre-selected population of adoptively transferred lymphocytes is activated by in vivo immunization, thereby increasing the effectiveness of adoptive immunotherapy.
Claims15
A method of preparing dual specificity T lymphocytes comprising:
- (i) contacting a population of T lymphocytes ex vivo with an allogeneic cell selected from the group consisting of dendritic cells, B lymphocytes and peripheral blood mononuclear cells (PBMCs), wherein contacting T lymphocytes with the allogeneic cell selects and specifically amplifies T lymphocytes comprising a T cell receptor that is reactive with the allogeneic cell;
- and
- (ii) transducing the T lymphocytes comprising the T cell receptor reactive with the allogeneic cell with a chimeric receptor gene, said gene encoding a chimeric fusion receptor between a single chain antibody that recognizes a tumor antigen and a T cell receptor capable of triggering T cell receptor signal transduction, which is reactive with a tumor antigen, to produce dual specificity T lymphocytes, wherein the dual specificity T lymphocytes generate an anti-tumor immune response in vivo.
Dependencies are inferred from the claim text.