Universal immune receptor expressed by T cells for the targeting of diverse and multiple antigens
The invention provides compositions and methods for adoptive T cell therapy in treating a variety of disorders including cancer, infections, and autoimmune disorders. In one embodiment, the invention provides a universal immune receptor (UnivIR) that comprises an extracellular label binding domain, a transmembrane domain, and a cytoplasmic domain or otherwise an intracellular domain.
1. A method for stimulating an immune response against a tumor antigen in a mammal having cancer, the method comprising
administering to a mammal an effective amount of a T cell genetically modified to express a biotin binding immune receptor (BBIR), wherein the BBIR comprises an extracellular binding domain, a transmembrane domain, a T cell receptor signaling domain, and an intracellular domain of a costimulatory molecule,
wherein the extracellular binding domain comprises avidin in monomeric, dimeric, or tetrameric form,
wherein the transmembrane domain is selected from the group consisting of alpha, beta or zeta chain of the T-cell receptor, CD3 epsilon, CD4, CD5, CD8, CD9, CD16, CD22, CD27, CD28, CD33, CD37, CD45, CD64, CD80, CD86, CD134, CD137, and CD154,
wherein the T cell receptor signaling domain is selected from the group consisting of CD3 zeta, ITAMs, TCR zeta, FcR gamma, FcR beta, CD3 gamma, CD3 delta, CD3 epsilon, CD5, CD22, CD79a, CD79b, and CD66d,
wherein the intracellular domain of a costimulatory molecule is selected from the group consisting of CD27, CD28, 4-1BB (CD137), OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, and B7-H3, and
further administering a biotinylated antibody or antibody fragment that specifically binds to a tumor antigen, wherein the BBIR binds to the biotinylated antibody or antibody fragment.
2. The method of claim 1 , wherein distinct tumor antigens are targeted sequentially or simultaneously.
3. The method of claim 1 , wherein the T cell is an autologous T cell.
4. The method of claim 1 , wherein the antibody or antibody fragment is selected from the group consisting of a monoclonal antibody, a Fab, and an scFv.
5. The method of claim 1 , wherein the BBIR comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 5-10.
6. The method of claim 1 , wherein the BBIR is encoded by a nucleotide sequence selected from the group consisting of SEQ ID NOs: 11-16.