US20250257133
2025-08-14
Chemistry; metallurgy
C07K16/2818
The disclosed invention focuses on anti-CD28 antibodies that specifically target human CD28, including their antigen-binding fragments. These antibodies are intended for use in compositions aimed at delaying or preventing tumor growth, offering a promising approach to cancer treatment. The invention is built upon the priority application PCT/CN2022/085838, and includes a sequence listing submitted in XML format, detailing the specific molecular sequences involved.
CD28 is a crucial costimulatory molecule found on T cells, essential for their activation, proliferation, and survival. While enhancing CD28 signaling can boost anti-tumor immunity, previous therapies have led to severe side effects such as cytokine storms and organ failure. The need for safer CD28-targeting therapies is evident to avoid these adverse effects while still harnessing the potential of T cell activation against tumors.
This invention introduces novel binding molecules that target both CD28 and tumor-associated antigens like B7-H3, HER2, TROP2, and PD-L1. These molecules are designed to provide enhanced clinical outcomes compared to existing cancer treatments. The antibodies or their fragments are cross-reactive with human, cynomolgus monkey, and mouse CD28, targeting specific epitopes within the CD28 molecule for precise therapeutic action.
The invention includes detailed sequences for the antigen-binding proteins, specifying the heavy and light chain variable domains (VH and VL) and complementarity-determining regions (CDRs). These sequences enable the development of antibodies with high specificity and effectiveness. Pharmaceutical compositions may include these antibodies alongside pharmaceutically acceptable carriers and can be produced using prokaryotic or eukaryotic host cells.
These antibodies can be used to treat cancer by administering them alone or in combination with other anti-cancer therapeutics such as bispecific antibodies targeting CD3 and tumor-associated antigens or immune checkpoint inhibitors. The invention also facilitates the creation of medicaments and kits for cancer treatment, offering a potentially safer alternative to systemic CD28 activation therapies.