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Assignees
Member
Icahn School of Medicine at Mount SinaiThe Icahn School of Medicine at Mount Sinai, located in New York City, is an international leader in biomedical education, research, and patient care. As the academic partner of the Mount Sinai Health System, the school is renowned for its innovative education, groundbreaking research, and commitment to health equity. With over 7,000 faculty, 1,200 students, and 2,500 residents and fellows, the institution fosters a culture of bold thinking, multidisciplinary teamwork, and a willingness to challenge conventional wisdom. Its mission is to radically advance the art and science of medical care through collaborative learning, scholarly inquiry, and a deep respect for diversity, preparing the next generation of healthcare leaders to revolutionize medicine and biomedical science.
The Icahn School of Medicine at Mount Sinai, located in New York City, is an international leader in biomedical education, research, and patient care. As the academic partner of the Mount Sinai Health System, the school is renowned for its innovative education, groundbreaking research, and commitment to health equity. With over 7,000 faculty, 1,200 students, and 2,500 residents and fellows, the institution fosters a culture of bold thinking, multidisciplinary teamwork, and a willingness to challenge conventional wisdom. Its mission is to radically advance the art and science of medical care through collaborative learning, scholarly inquiry, and a deep respect for diversity, preparing the next generation of healthcare leaders to revolutionize medicine and biomedical science.
Publication Number
US-12157768-B2
Publication Date
2024-12-03
Expiration Date
2039-09-17
Abstract
Antibodies and antibody fragments that specifically bind to LILRB2 are disclosed. Also provided herein are compositions comprising antibodies and antibody fragments that specifically bind to LILRB2 and methods of use thereof. Also provided are related chimeric antigen receptors (CARs) and cells comprising same (e.g., T cells, natural killer cells, or macrophages), and uses of the CARs and cells in targeting tumors and killing them, asthma treatment, or in targeting and removing infected cells (e.g., to treat infections or infectious diseases), or in suppressing immune system cells, as involved in autoimmune disease or transplant rejection.
Core Innovation
The invention introduces antibodies and antigen-binding fragments that specifically target LILRB2, a receptor involved in modulating immune responses. These antibodies can act as antagonists or agonists, thereby either stimulating or suppressing immune functions. The core innovation lies in the development of specific antibodies with defined sequences that can reprogram myeloid cell phenotypes, such as promoting pro-inflammatory M1 or suppressive M2 states, offering therapeutic potential in cancer, infections, and autoimmune diseases.
The invention further provides nucleic acids, vectors, and host cells for producing these antibodies, along with methods to manufacture and use them. This comprehensive set of tools enables the modulation of immune responses and the design of therapies targeting various diseases by controlling myeloid cell activity through specific LILRB2 engagement.
Claims Coverage
The independent claims define a range of antibodies or antigen-binding fragments that bind to LILRB2, characterized by specific heavy and light chain CDR sequences, as well as nucleic acids encoding these antibodies, vectors, host cells, pharmaceutical formulations, and methods of treatment. The claims also encompass chimeric antigen receptors (CARs) targeting LILRB2 for cell therapy.
Specific LILRB2 binding antibodies with defined CDR sequences
Antibodies or fragments thereof that bind to LILRB2 and include heavy and light chain variable regions with particular CDR sequences specified by SEQ ID NOs.
Nucleic acid molecules encoding anti-LILRB2 antibodies
Nucleic acids encoding the aforementioned antibodies, useful for recombinant production.
Vectors and host cells
Vectors containing nucleic acids for antibody expression and host cells engineered to produce the antibodies.
Methods of producing antibodies
Processes involving culturing host cells to produce the antibodies and methods for purification.
Pharmaceutical compositions
Formulations comprising anti-LILRB2 antibodies or fragments, with carriers suitable for administration via various routes and combined with other therapeutic agents.
Methods of treatment
Therapeutic protocols for treating cancer, infections, autoimmune diseases, or transplant rejection by administering the antibodies or CAR constructs, optionally in combination with immune checkpoint blockade therapies.
Overall, the claims cover a broad spectrum of anti-LILRB2 antibodies defined by specific sequence attributes, along with their nucleic acids, production methods, compositions, and therapeutic applications, including cell-based therapies such as CARs.
Stated Advantages
Anti-LILRB2 antagonists promote cytokine secretion such as TNF-alpha, boosting pro-inflammatory responses beneficial for cancer and infectious disease treatments.
Anti-LILRB2 agonists enhance IL-10 secretion, suppress T-cell proliferation, and are useful for immune suppression in autoimmune diseases and transplant rejection.
These antibodies can reprogram macrophages, shifting tumor-associated macrophages toward a pro-inflammatory M1 phenotype to enhance anti-tumor immunity.
They inhibit tumor growth and tumor-induced immunosuppression, especially when combined with immune checkpoint inhibitors like anti-PD-1 or anti-PD-L1.
They improve vaccine efficacy and bacterial phagocytosis, as well as demonstrate efficacy in humanized models.
CAR-T cells targeting LILRB2 exhibit specific activation, cytokine release, and cytotoxic activity against leukemia cells, reducing tumor burden. These benefits support their broad therapeutic potential in oncology, infectious diseases, and immune regulation.
Documented Applications
Treatment of cancers including lymphoma, leukemia, colon, breast, and lung cancers using anti-LILRB2 antibodies or CAR-T cells.
Enhancement of immune responses for bacterial infections and other infectious diseases.
Inhibition of inflammation, autoimmune disorders, and transplant rejection by modulating immune responses.
Combination therapies with immune checkpoint inhibitors such as PD-1 or PD-L1 blockers to improve anti-tumor efficacy.
Use of anti-LILRB2 CAR-T cells for targeting and eliminating tumor cells expressing LILRB2, such as leukemia or solid tumors like colon cancer.
Advancement of vaccine adjuvant strategies and bacterial clearance via antibody-mediated immune modulation.
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