Chimeric antigen receptors targeting B-cell maturation antigen
Inventors
Assignees
US Department of Health and Human Services
Publication Number
US-11827889-B2
Publication Date
2023-11-28
Expiration Date
2033-03-15
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
The invention provides an isolated and purified nucleic acid sequence encoding a chimeric antigen receptor (CAR) directed against B-cell Maturation Antigen (BCMA). The invention also provides host cells, such as T-cells or natural killer (NK) cells, expressing the CAR and methods for destroying multiple myeloma cells.
Core Innovation
The invention provides an isolated and purified nucleic acid sequence encoding a chimeric antigen receptor (CAR) directed against B-cell maturation antigen (BCMA). This CAR comprises an antigen recognition moiety and a T-cell activation moiety, where the antigen recognition moiety is specifically directed against BCMA. The invention also provides host cells such as T-cells or natural killer (NK) cells that express the CAR, and methods for destroying multiple myeloma cells by targeting BCMA-expressing cells.
Multiple myeloma is characterized by clonal plasma cell accumulation and currently lacks effective, FDA-approved monoclonal antibody or autologous T-cell therapies. Although adoptive T-cell therapies utilizing anti-CD19 CARs have shown promise in B-cell malignancies, CD19 is rarely expressed on multiple myeloma cells, highlighting the need for alternative targeted therapies. The invention addresses this need by providing compositions and methods involving CARs directed against BCMA, a molecule expressed on multiple myeloma cells but with a restricted expression pattern in normal tissues.
Claims Coverage
The patent includes one independent claim defining a method of treating multiple myeloma using human T-cells expressing a specific CAR. There is one main inventive feature described in the claim.
Method of treating multiple myeloma using CAR-expressing T-cells
The method involves administering to a human subject a pharmaceutical composition containing human T-cells that express a chimeric antigen receptor (CAR). The CAR comprises an antigen recognition moiety that binds human B-cell maturation antigen (BCMA), a CD8α hinge domain, a CD8α transmembrane domain, a 4-1BB intracellular T cell signaling domain, and a CD3ζ intracellular T cell signaling domain. The claim further specifies that the antigen recognition moiety can be an antigen-binding portion of an antibody including variable regions and complementarity determining regions (CDRs). The CAR may also include a CD8α signal sequence, with certain signaling and transmembrane domains corresponding to the sequences of SEQ ID NO: 10. The human T-cells can be autologous to the treated subject.
The claims cover a therapeutic method for treating multiple myeloma by administering human T-cells engineered to express a CAR targeting BCMA, comprising specific structural domains including CD8α hinge and transmembrane regions, 4-1BB and CD3ζ T cell signaling domains, with defined antigen recognition moieties, and optionally comprising a CD8α signal sequence.
Stated Advantages
The CARs provide targeted destruction of multiple myeloma cells by specifically recognizing BCMA, a molecule expressed on these cancer cells with restricted normal tissue expression.
The CARs avoid issues related to antigen processing and MHC restriction, allowing recognition of antigens independently of tumor escape mechanisms.
The invention enables adoptive cellular immunotherapy approaches that have shown promising in vivo efficacy in destroying established multiple myeloma tumors and extending survival in animal models.
Documented Applications
Treatment of multiple myeloma through adoptive transfer of T-cells or NK cells expressing the CAR directed against BCMA.
Destruction of established multiple myeloma tumors in vivo as demonstrated in murine models.
Potential treatment of Hodgkin's lymphoma by targeting BCMA expressed on Hodgkin's lymphoma cells.
Use in pharmaceutical compositions for administration to humans including autologous and allogeneic T-cell therapies.
Interested in licensing this patent?