Chimeric receptor genes and cells transformed therewith
AssigneesThe United States of America, as represented by the Secretary, Department of Health and Human Services, Yeda Research and Development Co. Ltd.
InventorsZelig Eshhar, Daniel Schindler, Tova Waks, Gideon Gross, Steven A. Rosenberg, Patrick Hwu
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Abstract
Chimeric receptor genes suitable for endowing lymphocytes with antibody-type specificity include a first gene segment encoding a single-chain Fv domain of a specific antibody and a second gene segment encoding all or part of the transmembrane and cytoplasmic domains, and optionally the extracellular domain, of an immune cell-triggering molecule. The chimeric receptor gene, when transfected to immune cells, expresses the antibody-recognition site and the immune cell-triggering moiety into one continuous chain. The transformed lymphocytes are useful in therapeutic treatment methods.
Claims30
An adoptive immunotherapeutic method of treating a patient having a cancer bearing tumor-specific antigen with cells having immunological specificity to a selected tumor-specific antigen, comprising administering to said patient cells that have been transformed with a chimeric gene, wherein said cells are peripheral blood lymphocytes, said chimeric gene containing a) a first DNA segment encoding a single-chain Fv (scFv) domain of an antibody directed against the selected tumor-specific antigen and b) a second DNA segment encoding a lymphocyte-activating molecule subunit of a Fc receptor to express the scFv domain and the lymphocyte-activating molecule on the surface of the lymphocytes and to provide said antibody-type specificity.
A method of treating a tumor in a patient, wherein said tumor bears immunologically reactive tumor-specific antigens, comprising:
- transforming cells of the patient with an expression vector wherein said cells are peripheral blood lymphocytes, said expression vector comprising a chimeric gene comprising a first gene segment encoding a single-chain Fv domain (scFv) of an antibody specific to a selected tumor-specific antigen and a second gene segment encoding a molecule selected from the group consisting of a subunit of a Fc receptor and an IL-2 receptor, to express both said scFv domain and said molecule, so that the transformed cells are activated and/or stimulated to proliferate, and exhibit MHC nonrestricted antibody-type specificity when said expressed scFv domain binds to its antigen, and administering the activated cells to the patient, said cells being targeted to the tumor cells, to provide tumor regression.
Dependencies are inferred from the claim text.