Cell therapy
AssigneeThe Walter and Eliza Hall Institute of Medical Research
InventorsStephen NUTT, Shengbo ZHANG, Michael CHOPIN
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Abstract
The present invention provides for chimeric antigen receptor constructs capable of being expressed in dendritic cells (DCs), and DCs modified to express one or more chimeric antigen receptors (CARs) as well as compositions comprising these modified DCs and methods of stimulating an adaptive immune response in a subject. The intracellular domain of the CAR comprises a toll-interleukin receptor (TIL) intracellular signalling domain and a costimulating domain selected from CD3 signalling domain, CD28 signalling domain and a combined CD28 and CD3 signalling domain.
Claims31
A chimeric antigen receptor (CAR) construct comprising:
- (i) an antigen-binding domain having binding affinity to a tumour cell antigen;
- (ii) a transmembrane domain (TM);
- and
- (iii) an intracellular domain (IC) comprising a toll-interleukin receptor (TIR) intracellular signalling domain;
- and a costimulatory signalling domain selected from a CD3 signalling domain, CD28 signalling domain and a combined CD28 and CD3 signalling domain,
- wherein the CAR construct is capable of being expressed and is functional in a dendritic cell.
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A method for making a chimeric antigen receptor containing dendritic cell (CAR-DC) population, comprising:
- (i) providing a population of cells from a subject;
- (ii) culturing the population of cells in a medium comprising an FMS-like tyrosine kinase 3 (Flt3) agonist for at least one day;
- (iii) introducing into the population of cells a chimeric antigen receptor (CAR) comprising an antibody or antigen-binding fragment thereof having binding affinity to a tumour cell antigen, a transmembrane domain (TM), and an intracellular domain (IC) comprising a toll-interleukin receptor (TIR) intracellular signalling domain and a costimulatory signalling domain selected from a CD3 signalling domain, CD28 signalling domain and a combined CD28 and CD3 signalling domain, wherein the TIR signalling domain is situated after the costimulatory signally domain at the C-terminal end of the CAR;
- and
- (iv) culturing the cells from (iii) in a medium comprising an FMS-like tyrosine kinase 3 (Flt3) agonist for an amount of time sufficient to form a modified dendritic cell.
Dependencies are inferred from the claim text.