Anti-CD276 polypeptides, proteins, and chimeric antigen receptors
Inventors
Orentas, Rimas J. • Zhu, Zhongyu • Mackall, Crystal L. • Dimitrov, Dimiter S. • St. Croix, Bradley • Saha, Saurabh
Assignees
National Institutes of Health NIH • Biomed Valley Discoveries Inc • US Department of Health and Human Services
Publication Number
US-10604583-B2
Publication Date
2020-03-31
Expiration Date
2034-03-24
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Polypeptides and proteins that specifically bind to and immunologically recognize CD276 are disclosed. Chimeric antigen receptors (CARs), anti-CD276 binding moieties, nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the polypeptides and proteins are also disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.
Core Innovation
The invention provides polypeptides and proteins comprising antigen binding domains of anti-CD276 antibodies that specifically recognize and bind to CD276, also known as B7-H3. These polypeptides and proteins target CD276-expressing cancer cells and may elicit an antigen-specific immune response against CD276. Such responses can target and destroy CD276-expressing cancer cells, reduce or eliminate cancer cells, facilitate infiltration of immune cells or effector molecules to tumor sites, and enhance or extend anti-cancer responses.
The invention further includes chimeric antigen receptors (CARs) comprising antigen binding domains from anti-CD276 antibodies, a transmembrane domain, and an intracellular T cell signaling domain. These CARs redirect T-cell specificity and reactivity toward CD276 in a non-MHC-restricted manner, allowing immune recognition of antigen independent of antigen processing, thus bypassing a major tumor escape mechanism. The CARs specifically bind and immunologically recognize CD276, eliciting antigen-specific immune responses to target and destroy CD276-expressing cancer cells, reduce or eliminate cancer cells, facilitate immune cell infiltration to tumor sites, and enhance or extend anti-cancer responses.
Claims Coverage
The patent contains multiple independent claims covering polypeptides, proteins, chimeric antigen receptors (CARs), nucleic acids, recombinant expression vectors, host cells, and populations of cells related to anti-CD276 binding domains.
Polypeptides comprising heavy and light chains binding to CD276 linked to immunoglobulin constant domains
A polypeptide comprising heavy and light chains with specified SEQ ID NOs (1-6, 11-16, or 20-25) that bind to CD276 and are linked to one or more immunoglobulin constant domains CH2 and/or CH3.
Proteins comprising two polypeptide chains binding to CD276 linked to immunoglobulin constant domains
A protein comprising a first polypeptide chain (heavy chain) and a second polypeptide chain (light chain) with specified SEQ ID NOs that bind to CD276 and are linked to one or more immunoglobulin constant domains CH2 and/or CH3.
Polypeptides comprising linker amino acid sequences
Polypeptides as above further comprising a linker amino acid sequence, including specifically SEQ ID NO: 115, linking variable regions.
Chimeric antigen receptors with anti-CD276 antigen binding domains and intracellular signaling domains
A CAR comprising an antigen binding domain formed by heavy and light chains binding to CD276 with specified SEQ ID NOs (1-6, 11-16, or 20-25), an immunoglobulin constant domain (including CH2 and/or CH3), a transmembrane domain comprising CD8 and/or CD28 sequences, and an intracellular T cell signaling domain comprising one or more of CD28, CD137, and CD3 zeta domains with specified sequences.
Nucleic acids encoding polypeptides binding CD276
Nucleic acid molecules comprising nucleotide sequences encoding the polypeptides comprising heavy and light chains that bind CD276 as described above.
Recombinant expression vectors comprising nucleic acids encoding anti-CD276 polypeptides
Recombinant expression vectors comprising the nucleic acid sequences encoding the polypeptides targeting CD276.
Host cells and populations of cells comprising recombinant vectors
Isolated host cells comprising recombinant expression vectors encoding the anti-CD276 polypeptides and populations of cells comprising at least one such host cell.
Polypeptides expressed in host cells for treating cancer
Polypeptides of the invention expressed in host cells used for treating cancer in a mammal.
The independent claims cover polypeptides and proteins comprising anti-CD276 heavy and light chain binding domains linked to immunoglobulin constant domains, chimeric antigen receptors including antigen binding, transmembrane, and intracellular signaling domains, nucleic acids encoding these polypeptides, recombinant expression vectors, host cells, and cell populations, all directed to specifically bind CD276 and mediate immune activity.
Stated Advantages
Specifically recognize and bind CD276, enabling targeted immune responses against CD276-expressing cancer cells.
Bypass major tumor escape mechanisms through non-MHC-restricted antigen recognition by CARs.
Elicit antigen-specific immune responses that can target and destroy cancer cells, reduce or eliminate cancer, facilitate immune cell infiltration to tumor sites, and enhance or extend anti-cancer effects.
Extend the binding motif of the antigen binding domain away from the cell membrane to more accurately mimic native T cell receptor domain structures.
Documented Applications
Detecting the presence of cancer in a mammal by contacting a sample of cells with anti-CD276 materials and detecting complex formation indicative of cancer presence.
Treating or preventing cancer in a mammal by administering polypeptides, proteins, CARs, nucleic acids, recombinant vectors, host cells, or pharmaceutical compositions targeting CD276 in effective amounts.
Use in immunotherapy for pediatric solid tumors, adult carcinomas, neuroblastoma, Ewing's sarcoma, rhabdomyosarcoma, and prostate, ovarian, colorectal, and lung cancers characterized by CD276 expression or overexpression.
Interested in licensing this patent?