Anti-CD30 chimeric antigen receptors
Inventors
Assignees
US Department of Health and Human Services
Publication Number
US-10815301-B2
Publication Date
2020-10-27
Expiration Date
2036-10-10
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Chimeric antigen receptors (CARs) that specifically bind to and immunologically recognize CD30 are disclosed. Related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CARs are also disclosed. Methods of treating or preventing a condition in a mammal, wherein the condition is cancer, are also disclosed.
Core Innovation
Chimeric antigen receptors (CARs) that specifically bind to and immunologically recognize CD30 are disclosed, including related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions. The CARs comprise an anti-CD30 antigen binding domain with human heavy and light chain complementarity determining regions (CDRs), a human hinge domain, a human transmembrane domain, and one or both of a human intracellular T cell signaling domain and a human T cell costimulatory domain. Methods of treating or preventing cancer, particularly lymphoma, by utilizing these CARs are also disclosed.
The problem being solved is the need for additional treatments for cancer, especially lymphoma, due to the poor prognosis of many cancers despite advances in treatments such as chemotherapy. The invention addresses the unmet need by providing CARs that target CD30, a molecule expressed or overexpressed by various human cancers, including lymphomas. These CARs enable an antigen-specific immune response against CD30-expressing cancer cells, aiming to target and destroy such cells, reduce tumor burden, facilitate infiltration of immune cells to tumor sites, and enhance anti-cancer responses.
The CARs are designed primarily with human sequences to reduce undesired immune responses upon administration to human patients compared to CARs containing non-human sequences. The antigen binding domain may use the 5F11 human antibody, which specifically binds CD30, in configurations such as single chain variable fragments. The CARs include domains from human CD8α, CD28, 4-1BB, and CD3ζ to facilitate effective T cell signaling and co-stimulation. Functional variants with sequence identities to the parent CARs are contemplated, retaining biological activity. The CARs can be produced synthetically or recombinantly, incorporated into nucleic acids or vectors, expressed in host cells including T cells, and formulated into pharmaceutical compositions for administration.
Claims Coverage
The patent includes one independent claim directed to a chimeric antigen receptor (CAR) with specificity for CD30, along with related claims covering nucleic acids, vectors, host cells, compositions, and methods of treatment.
Chimeric antigen receptor with anti-CD30 antigen binding domain
A CAR comprising an anti-CD30 antigen binding domain containing heavy chain CDR1 (SEQ ID NO: 1), CDR2 (SEQ ID NO: 2), CDR3 (SEQ ID NO: 3), and light chain CDR1 (SEQ ID NO: 4), CDR2 (SEQ ID NO: 5), CDR3 (SEQ ID NO: 6).
Distinct intracellular signaling and structural domains in the CAR
The CAR includes either (b) a hinge domain, transmembrane domain, and intracellular T cell signaling domain of human CD28 plus an intracellular T cell signaling domain of human CD3ζ; or (c) a hinge and transmembrane domain of human CD8α, an intracellular T cell signaling domain of human CD28, and an intracellular domain of human CD3ζ.
CAR comprising specified amino acid sequences
The CAR comprises amino acid sequences SEQ ID NOs: 7 and 8 for antigen binding domain; SEQ ID NO: 11 for hinge and transmembrane; SEQ ID NOs: 12 and 15 for intracellular domains; including embodiments with sequences of SEQ ID NOs: 16, 17, and 18 corresponding to specific CAR constructs.
Nucleic acid encoding the CAR
A nucleic acid comprising a nucleotide sequence encoding the CAR of claim 1.
Recombinant expression vector comprising said nucleic acid
A recombinant expression vector comprising the nucleic acid encoding the CAR.
Host cell comprising the recombinant expression vector
A host cell containing the recombinant expression vector encoding the CAR.
Population of host cells
A population comprising at least two host cells each comprising the recombinant expression vector encoding the CAR.
Pharmaceutical compositions containing the CAR or host cells
Pharmaceutical compositions comprising the CAR or the population of host cells and a pharmaceutically acceptable carrier.
Method of treating cancer using host cells expressing the CAR
Administering to a mammal an effective amount of one or more host cells expressing the CAR, where host cells are natural killer (NK) cells or T cells, to treat cancer, specifically lymphoma; cells may be autologous or allogeneic.
The independent claim covers a CAR with anti-CD30 specificity containing defined human CDRs and signaling domains from CD28 and CD3ζ, with claims extending to nucleic acids, vectors, host cells, pharmaceutical compositions, and methods of treating cancer, especially lymphoma, using cells expressing the CAR.
Stated Advantages
All or nearly all components of the CARs being human sequences may reduce undesirable immune responses in human patients compared to CARs containing non-human sequences.
The CARs provide non-MHC-restricted antigen recognition, enabling immune cells expressing CARs to recognize target antigens independent of antigen processing and reducing tumor escape.
CARs elicit antigen-specific immune responses against CD30-expressing cancer cells, potentially targeting and destroying such cells, reducing or eliminating cancer, facilitating immune cell infiltration to tumor sites, and enhancing or extending anti-cancer responses.
Documented Applications
Treatment or prevention of cancer in mammals, particularly lymphomas characterized by CD30 expression or overexpression.
Use in adoptive cell transfer (ACT) therapy by administering T cells or NK cells genetically modified to express the CARs to mediate antigen-specific immune responses against CD30+ cancers.
Pharmaceutical compositions comprising the CARs or host cells expressing them for parenteral administration, including intravenous injection.
Interested in licensing this patent?