Reagents and methods for treating cancer and autoimmune disease

Inventors

Lai, Laijun

Assignees

University of Connecticut

Abstract

Disclosed herein are methods for treating cancer by administering to a subject having cancer antibodies against one or more of CD300c, BTN5 (Erythroid membrane-associated protein), TAPBPL (antigen processing (TAP) binding protein like protein), Skint8 (selection and upkeep of intraepithelial T cells 8 protein), and CD300f. Also disclosed herein are methods for treating autoimmune diseases by administering to a subject having an autoimmune disease an IgV domain, or a nucleic acid encoding an IgV domain, from one or more of CD300c, BTN5, TAPBPL, SkintS, and CD300f. Also disclosed herein are antibodies against CD300c and TAPBPL, and fusion proteins that can be used in the methods for treating autoimmune disease.

Core Innovation

The disclosure describes immunotherapy methods and biologics that target immune inhibitory pathways for cancer therapy and autoimmune disease therapy. It provides isolated antibodies and antibody fragments that selectively bind human CD300c, and TAPBPL targeting using a TAPBPL-Ig fusion protein, including hTAPBPL-Ig, to suppress T cell proliferation and activation.

For cancer therapy, the disclosed antibodies selectively bind an extracellular domain (ECD) of human CD300c and are described with CDR-defined heavy and light chain sequences. The content also states that an anti-TAPBPL monoclonal antibody neutralizes TAPBPL-mediated T cell inhibition and suppresses tumor growth in a leukemia model, and includes anti-tumor activity using anti-CD300c or anti-TAPBPL antibodies and related Ig fusion formats.

For autoimmune disease therapy, the disclosure provides IgV domains, nucleic acids or expression vectors encoding them, directed to immune inhibitory targets including CD300c, TAPBPL, and Skint8, together with fusion molecules and Fc/heterologous-polypeptide fusion constructs. The described biologics are characterized using functional readouts including suppression of T-cell proliferation, T-cell activation, cytokine production, attenuation of GVHD and autoimmune disease phenotypes such as EAE and CIA, and changes involving CD69, CD44, CD62L, and regulatory T cells.

Claims Coverage

The consolidated content provides two independent claims centered on a CDR-defined anti-CD300c antibody, plus a method claim applying that antibody to treating colon cancer or melanoma. No independent TAPBPL claim is explicitly described in the provided claims content.

Across the independent claims, the core coverage is a selectively binding anti-human CD300c antibody defined by specified heavy- and light-chain CDR sequences, and a treatment method administering that CDR-defined antibody for colon cancer or melanoma. Dependent claim elements further refine antibody sequence similarity, antibody format, and binding specificity constraints using extracellular-region or IgV domain residue ranges.

Stated Advantages

Documented Applications