Chimeric antigen receptors (CARs), targeting hematologic malignancies, compositions and methods of use thereof
AssigneeiCell Gene Therapeutics Inc.
InventorsYupo Ma, Kevin Pinz, Xun Jiang, Masayuki Wada, Kevin Chen
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Abstract
The present disclosure provides chimeric antigen receptor polypeptides having antigen recognition domains for CD2, CD3, CD4, CD5, CD7, CD8, and CD52 antigens, and polynucleotides encoding for the same. The present disclosure also provides for engineered cells expressing the polynucleotide or polypeptides. In some embodiments, the disclosure provides methods for treating diseases associated with CD2, CD3, CD4, CD5, CD7, CD8, and CD52 antigens.
Claims20
An in vitro method of reducing the number of CD4 positive T cell leukemia cells or CD4 positive T cell lymphoma cells, the method comprising the steps of:
- (i) contacting a plurality of cells comprising CD4 positive T cell leukemia cells or CD4 positive T cell lymphoma cells with an effective amount of engineered cells comprising a polynucleotide that encodes for a chimeric antigen receptor (CAR) polypeptide comprising:
- a signal peptide, a CD4 antigen recognition domain, a hinge region, a transmembrane domain, at least one co-stimulatory domain, and a signaling domain;
- said polynucleotide comprises the nucleotide of SEQ ID NO:4 or SEQ ID NO:5, wherein the CD4 antigen recognition domain specifically recognizes CD4 in a target cell population;
- and
- (ii) optionally, assaying for CD4 positive T cell leukemia cells or CD4 positive lymphoma cells;
- wherein the engineered cells comprise at least one of CD8 T-cells, Natural Killer cells, and Natural Killer T cells (NKT cells);
- and wherein the number of CD4 positive T cell leukemia cells or CD4 positive T cell lymphoma cells are reduced by at least 5% as compared to the number of CD4 positive T cell leukemia cells or CD4 positive T cell lymphoma cells prior to the contacting of step (i).
A method of treating a CD4 associated cell proliferative disease in a human patient in need thereof, the method comprising the steps of:
- (i) obtaining T cells from said human patient;
- (ii) transforming said T cells with a polynucleotide encoding a CD4CAR polypeptide comprising a signal peptide, a CD4 antigen recognition domain that specifically recognizes CD4 in a target cell population, a hinge region, a transmembrane domain, at least one co-stimulatory domain, and a signaling domain;
- to provide engineered cells that express a chimeric antigen receptor (CAR);
- (iii) administering to said human patient in need thereof a therapeutically effective amount of the engineered cells of step (ii);
- (iv) reducing the tumor burden of CD4 associated cell proliferative disease cells;
- and
- (v) optionally, assaying for CD4 positive cells associated with the cell proliferative disease;
- wherein the human patient in need thereof comprises a human patient who is suffering from a CD4 associated cell proliferative disease;
- and wherein the engineered cells comprise at least one of CD8 T-cells, and Natural Killer T cells (NKT cells);
- and said polynucleotide comprises the nucleotide of SEQ ID NO:4 or SEQ ID NO:5.
A method of treating a CD4 associated cell proliferative disease in a human patient in need thereof, the method comprising the steps of:
- administering to said human patient in need thereof a therapeutically effective amount of an engineered Natural Killer cell comprising:
- a polynucleotide encoding a CD4CAR polypeptide comprising a signal peptide, a CD4 antigen recognition domain, a hinge region, a transmembrane domain, at least one co-stimulatory domain, and a signaling domain, wherein the CD4 antigen recognition domain specifically recognizes CD4 in a target cell population, and said polynucleotide comprises the nucleotide sequences of SEQ ID NO. 4 or SEQ ID NO. 5;
- wherein the patient in need thereof comprises a patient who is suffering from a CD4 associated cell proliferative disease;
- and wherein the number of CD4 associated cell proliferative disease cells are reduced by at least 5% as compared to the number of CD4 associated cell proliferative disease cells prior to administering said engineered Natural Killer cell.
Dependencies are inferred from the claim text.