Chimeric antigen receptor polypeptides in combination with trans metabolism molecules modulating Krebs cycle and therapeutic uses thereof
AssigneeSotio Biotech Inc.
InventorsKathleen McGinness, Seth Ettenberg, Luke Barron, Michael Fray, Charles Wilson, Gregory Motz
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Abstract
Disclosed herein are genetically engineered hematopoietic cells, which express one or more Krebs cycle modulating polypeptides, and optionally a chimeric receptor polypeptide (e.g., an antibody-coupled T cell receptor (ACTR) polypeptide or a chimeric antigen receptor (CAR) polypeptide) capable of binding to a target antigen of interest. Also disclosed herein are uses of the engineered hematopoietic cells for inhibiting cells expressing a target antigen in a subject in need thereof.
Claims23
A genetically engineered hematopoietic cell, which has a modulated Krebs cycle as compared with a native hematopoietic cell of the same hematopoietic cell type;
- wherein the genetically engineered hematopoietic cell expresses:
- (i) a Krebs cycle modulating polypeptide, which is glutamic-oxaloacetic transaminase (GOT), isocitrate dehydrogenase (IDH), malate dehydrogenase (MDH), phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase (PSAT1), glutamate dehydrogenase (GDH1), glutamate-pyruvate transaminase 1 (GPT1), or glutaminase (GLS);
- and
- (ii) a chimeric receptor polypeptide, which comprises
- (a) an extracellular target binding domain;
- (b) a transmembrane domain;
- and
- (c) a cytoplasmic signaling domain;
- and
- wherein the Krebs cycle modulating polypeptide is encoded by an exogenous nucleic acid;
- and wherein the transmembrane domain is from a membrane protein selected from the group consisting of CD8α, CD8β, CD137, CD27, CD28, CD34, CD4, FcεR1γ, CD16, CD134, CD32, CD64, CD45, CD5, CD9, CD22, CD37, CD80, CD86, CD40, CD154, VEGFR2, FAS, and FDFR2B.
Dependencies are inferred from the claim text.