Genetically modified ungulate cells and their uses in cancer therapy
AssigneesImanis Life Sciences, LLC, Mayo Foundation for Medical Education and Research, Fios Therapeutics LLC
InventorsStephen J. Russell, Karina Krotova, Christopher G.A. McGregor
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Abstract
Provided herein are genetically modified ungulate cells expressing a chimeric antigen receptor. Also provided herein are transgenic ungulate cells that can be used as cell carriers for the delivery of oncolytic viruses in cancer therapy. Also provided are transgenic ungulates comprising these cells, methods of making these cells, and methods of treating cancer by administering these cells to a subject in need thereof. Also provided are transgenic ungulate cells that express a chimeric antigen receptor and uses thereof.
Claims91
A genetically modified ungulate cell comprising a nucleic acid encoding a chimeric antigen receptor (CAR).
A method for activating ungulate T cells comprising:
- (a) obtaining a population of ungulate T cells;
- and
- (b) contacting the population of ungulate T cells with a population of artificial antigen presenting cells, wherein the antigen presenting cells express ungulate CD80, ungulate CD83, and an anti-ungulate CD3 antibody.
A genetically modified ungulate cell comprising an oncolytic virus, wherein the cell is derived from a transgenic ungulate.
The genetically modified, ungulate cell of any one of claims 39-50, wherein the cell is genetically modified to express a chimeric antigen receptor (CAR).
A genetically modified ungulate cell comprising a chimeric antigen receptor (CAR), wherein the cell is derived from a transgenic ungulate.
A transgenic ungulate comprising:
- (a) two or more genetic modifications to reduce rejection of a cell or tissue derived from the transgenic ungulate when transplanted into a human host, wherein the modifications are selected from the group consisting of a modification that reduces expression of alpha 1,3 galactosyltransferase;
- a modification that reduces expression of beta-2-microglobulin;
- a modification that reduces expression of T cell receptor alpha;
- a modification that reduces expression of T cell receptor beta;
- a modification that reduces expression of class II, major histocompatibility complex;
- a modification that reduces expression of transactivator (CIITA);
- and an insertion of a nucleic acid sequence encoding a HLA-E-beta2M single chain trimer;
- and
- (b) optionally comprising a nucleic acid sequence encoding a heterologous polypeptide.
A method for producing a genetically modified, ungulate cell as a carrier for an oncolytic virus, comprising:
- (a) obtaining a cell or population of cells from a transgenic ungulate that is genetically modified to reduce rejection of a cell or tissue derived from the transgenic ungulate when transplanted into a human host and
- (b) infecting the cell or population of cells with an oncolytic virus.
A method for producing a genetically modified, ungulate cell expressing a chimeric antigen receptor (CAR), comprising:
- (a) introducing in vitro a nucleic acid encoding the CAR into a cell or population of cells derived from a transgenic ungulate genetically modified to reduce rejection of a cell or tissue derived from the transgenic animal when transplanted into a human host;
- or
- (b) obtaining a cell or population of cells from a transgenic ungulate that is genetically modified to:
- (i) express a CAR;
- and
- (ii) genetically modified to reduce rejection of a cell or tissue derived from the transgenic ungulate when transplanted into a human host.
Dependencies are inferred from the claim text.