Compositions and methods for modulating LAIR signal transduction
Inventors
FLIES, DALLAS BENJAMIN • Liu, Linda • Langermann, Solomon
Assignees
Publication Number
US-12084495-B2
Publication Date
2024-09-10
Expiration Date
2037-08-03
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Compositions and methods of use thereof for modulating LAIR-1 are provided. For example, immunomodulatory agents are provided that reduce LAIR-1 expression, ligand binding, crosslinking, negative signaling, or a combination thereof. Such agents can be used to increase an immune response in a subject in need thereof. Exemplary agents include (i) a soluble LAIR-2 polypeptide or fusion protein, (ii) a soluble LAIR-1 polypeptide or fusion protein, (iii) a function blocking anti-LAIR-1 antibody, (iv) an antibody that depletes LAIR-1 positive cells, and (y) combinations thereof. Immunomodulatory agents are also provided that increase LAIR-1 expression, ligand binding, crosslinking, negative signaling, or a combination thereof. Such agents can be used to reduce an immune response in a subject in need thereof. Exemplary agents include: (i) a function activating anti-LAIR-1 antibody, (ii) a function blocking anti-LAIR-2 antibody, and (iii) a combination thereof.
Core Innovation
This invention provides compositions and methods for modulating LAIR-1 signal transduction using specific immunomodulatory agents. The agents include, for example, fusion proteins comprising soluble forms of LAIR-2 or LAIR-1 linked to immunoglobulin domains, function blocking or activating anti-LAIR-1 antibodies, antibodies that deplete LAIR-1 positive cells, and combinations thereof. Such agents are designed to either reduce or increase LAIR-1 activity, thereby modulating immune responses in treated subjects.
The problem addressed is the need for effective means to either increase or decrease immune responses through direct modulation of LAIR-1, particularly for the treatment of inflammatory and autoimmune diseases, cancer, and infectious diseases. Current understanding highlights the regulatory role of LAIR-1 as an inhibitory receptor on various immune cells and its involvement in maintaining immune homeostasis and influencing leukemic cell survival and self-renewal.
The provided solutions allow for increasing immune responses by blocking LAIR-1 with function-blocking antibodies or by using LAIR-2 decoy fusion proteins, which serve to disrupt inhibitory signaling mediated by LAIR-1. Conversely, agents that stimulate LAIR-1, such as activating antibodies or blocking LAIR-2, can suppress excessive immune activity, useful for treating autoimmune or inflammatory conditions. The patent further details the design, production, and use of these agents, including their specific sequences, formulations, and application in therapy.
Claims Coverage
The independent claims cover inventive features directed to pharmaceutical compositions comprising a defined LAIR-2 fusion protein and anti-PD-1 immunotherapy, as well as methods of promoting immune responses and reducing tumor burden using these compositions.
Pharmaceutical composition comprising LAIR-2 fusion protein and anti-PD-1 immunotherapy
A pharmaceutical composition includes a fusion protein having the amino acid sequence of SEQ ID NO:16 (which is a LAIR-2 polypeptide fused to a human IgG1 Fc domain) in combination with an anti-PD-1 immunotherapy. The composition may optionally include: - A vector encoding the fusion protein. - An expression vector. - A cell expressing the fusion protein, such as a Chinese hamster ovary cell. - Formulation for parenteral administration. - The anti-PD-1 immunotherapeutic can be an anti-PD-1 antibody.
Method for promoting primary T cell proliferation using the pharmaceutical composition
A method is provided for promoting primary T cell proliferation in a subject in need thereof by administering an effective amount of the pharmaceutical composition containing both the LAIR-2 fusion protein (SEQ ID NO:16) and anti-PD-1 immunotherapy.
Method for promoting antigen-specific CD8+ T cell expansion
A method comprises administering the pharmaceutical composition (LAIR-2 fusion protein and anti-PD-1 immunotherapy) to a subject in need thereof, in an effective amount to promote antigen-specific CD8+ T cell expansion.
Method for reducing tumor burden using the LAIR-2 fusion protein/anti-PD-1 composition
A method for reducing tumor burden involves administering the pharmaceutical composition comprising LAIR-2 fusion protein (SEQ ID NO:16) and anti-PD-1 immunotherapy to a subject in need thereof in an effective amount. The tumor can be ovarian tumor or lymphoma.
The claims encompass pharmaceutical compositions that combine a specified LAIR-2 fusion protein and anti-PD-1 immunotherapy, as well as their delivery as a gene or as protein from an expression system, and methods for using these compositions to stimulate specific T cell responses and reduce tumor burden.
Stated Advantages
The compositions can increase or enhance immune responses, such as primary T cell proliferation and antigen-specific CD8+ T cell expansion, providing improved immune function in the treated subject.
The pharmaceutical compositions reduce tumor burden, including effectiveness in ovarian tumors and lymphoma.
Documented Applications
Use in cancer immunotherapy, specifically for reducing tumor burden in ovarian tumors and lymphoma.
Promoting primary T cell proliferation and antigen-specific CD8+ T cell expansion in a subject.
Interested in licensing this patent?