Engineered effector cells and methods of enhancing ubiquitous targeting of solid tumors
AssigneeFate Therapeutics, Inc.
InventorsJohn Charles GOULDING, Bahram VALAMEHR, Martin HOSKING, Ryan BJORDAHL
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Abstract
Provided are methods and compositions for obtaining functionally enhanced derivative effector cells obtained from directed differentiation of genomically engineered iPSCs. Also provided are derivative cells having stable and functional genome editing that delivers improved or enhanced therapeutic effects. Also provided are therapeutic compositions and the use thereof comprising the functionally enhanced derivative effector cells alone, or with antibodies or checkpoint inhibitors in combination therapies.
Claims67
A composition comprising a cell or population thereof, wherein the cell is an immune cell, an induced pluripotent cell (iPSC) or a derivative cell obtained from differentiating the iPSC;
- and wherein the cell comprises a MICA/B tumor antigen targeting specificity;
- wherein the cell optionally comprises one or more exogenous polynucleotides encoding a MICA/B-CAR (chimeric antigen receptor), a CD16 or a variant thereof that mediates ADCC when in combination with an anti-MICA/B antibody, an exogenous TCR targeting a MICA/B tumor antigen, or any combination thereof;
- and wherein:
- (i) the cell or population thereof further comprises a CAR having a tumor antigen targeting specificity other than MICA/B, or
- (ii) the composition further comprises a sensitizing agent, wherein the sensitizing agent increases tumor cell surface levels of MICA/B.
The method of claim of 27, wherein the method further comprises administering one or more therapeutic agents to the subject.
A method of treating a subject comprising:
- (a) administering a sensitizing agent to the subject to precondition tumor cells in the subject;
- and
- (b) administering a cell or population thereof to the subject following preconditioning the tumor cells, wherein the cell is an immune cell or a derivative cell obtained from differentiating an iPSC;
- wherein the cell comprises a MICA/B tumor antigen targeting specificity;
- and wherein the cell optionally comprises one or more exogenous polynucleotides encoding a MICA/B-CAR (chimeric antigen receptor), a CD16 or a variant thereof that mediates ADCC when in combination with an anti-MICA/B antibody, an exogenous TCR targeting a MICA/B tumor antigen, or any combination thereof,
- wherein the subject has an autoimmune disorder;
- a hematological malignancy;
- a solid tumor;
- cancer, or a virus infection.
A method of treating a subject comprising:
- administering a cell or population thereof to the subject, wherein the cell is an immune cell or a derivative cell obtained from differentiating an iPSC, wherein the cell:
- (a) comprises a MICA/B tumor antigen targeting specificity;
- and
- (b) comprises an exogenous polynucleotide encoding a CAR having specificity to a tumor antigen other than MICA/B;
- and optionally wherein the MICA/B tumor antigen targeting specificity comprises one or more exogenous polynucleotides encoding:
- (i) a MICA/B-CAR (chimeric antigen receptor);
- (ii) a CD16 or a variant thereof that mediates ADCC when in combination with an anti-MICA/B antibody;
- (iii) an exogenous TCR targeting a MICA/B tumor antigen;
- or (iv) any combination thereof;
- and
- wherein the subject has an autoimmune disorder;
- a hematological malignancy;
- a solid tumor;
- cancer, or a virus infection.
A method of enhancing tumor surface MICA/B expression and/or density comprising contacting a tumor cell with a sensitizing agent, thereby increasing surface MICA/B expression as compared to MICA/B expression prior to contact with the sensitizing agent.
Dependencies are inferred from the claim text.