Use of endogenous viral vaccine in chimeric antigen receptor T cell therapy
AssigneeCity of Hope
InventorsJohn C. Williams, Christine Brown, Don J. Diamond
Life of this patent
Estimating the term…
Abstract
Provided herein are, inter alia, methods and compositions including T cells expressing (i) a recombinant CAR protein which includes a peptide binding site and is capable of specifically binding cancer-specific antigens and (ii) a T cell receptor specific for a viral antigen (e.g., a CMV pp65 protein). The engineered T cells provided herein may be used in combination with a viral vaccine (e.g. cytomegalovirus (CMV) Triplex Vaccine) to treat a variety of cancers. The methods described herein also permit in vivo expansion of CMV-specific CAR T cells, instead of or in addition to ex vivo expansion, avoiding excessive T cell exhaustion that results in some cases from ex vivo manufacturing.
Claims10
A method for forming a population of human T cells expressing a recombinant CAR protein and a T cell receptor specific for a CMV antigen, said method comprising:
- (1) administering a viral vector encoding:
- (a) a CMV pp65 protein and (b) a fusion protein comprising exon 4 of CMV protein IE1 (e4) and exon 5 of CMV protein IE2 (e5) to a CMV-seronegative human donor;
- (2) obtaining PBMCs from said human donor;
- (3) contacting said PBMCs with at least one CMV antigen;
- (3) allowing said contacted cells to produce a population of cells enriched for stimulated cells specific for CMV;
- (4) transducing at least a portion of said enriched population of cells with a vector expressing a recombinant CAR protein, thereby forming a population of human T cells expressing a T cell receptor specific for a CMV antigen and a recombinant CAR protein.
A method for forming a population of human T cells expressing a recombinant CAR protein and a T cell receptor specific for a CMV antigen, said method comprising:
- (1) administering a viral vector encoding:
- (a) a CMV pp65 protein and (b) a fusion protein comprising exon 4 of CMV protein IE1 (e4) and exon 5 of CMV protein IE2 (e5) to a CMV-seropositive human donor;
- (2) obtaining PBMCs from said CMV-seropositive human donor;
- (3) contacting said PBMCs with at least one CMV antigen;
- (4) allowing said contacted cells to produce a population of cells enriched for stimulated cells specific for CMV;
- (5) transducing at least a portion of said enriched population of cells with a vector expressing a recombinant CAR protein, thereby forming a population of human T cells expressing a T cell receptor specific for a CMV antigen and a recombinant CAR protein.
Dependencies are inferred from the claim text.