Chimeric antigen receptor
The present invention provides a chimeric antigen receptor (CAR) comprising; (i) a B cell maturation antigen (BCMA)-binding domain which comprises at least part of a proliferation-inducing ligand (APRIL); (ii) a spacer domain (iii) a transmembrane domain; and (iv) an intracellular T cell signaling domain. The invention also provides the use of such a T-cell expressing such a CAR in the treatment of plasma-cell mediated diseases, such as multiple myeloma.
1. A chimeric antigen receptor (CAR) which comprises:
(i) truncated proliferation-inducing ligand (APRIL) that
(a) binds B cell maturation antigen (BCMA) and
(b) binds transmembrane activator and calcium modulator and cylophilin ligand interactor (TACI);
(ii) a spacer domain; and
(ii) a transmembrane domain; and
(iii) an intracellular T cell signaling domain.
2. The CAR according to claim 1 , wherein the truncated APRIL lacks the amino terminal portion of APRIL responsible for proteoglycan binding.
3. The CAR according to claim 2 , which comprises the sequence shown as SEQ ID No. 14.
4. The CAR according to claim 1 , wherein the transmembrane and intracellular T-cell signalling domain comprise the sequence shown as SEQ ID No. 7.
5. The A CAR according to claim 1 , wherein the spacer comprises one of the following: a human IgG1 spacer; an IgG1 hinge; or a CD8 stalk.
6. The CAR according to claim 5 , wherein the spacer comprises a CD8 stalk.
7. The CAR according to claim 1 , which comprises the sequence shown as SEQ ID No. 1, 2, 3, 4, 5 or 6.