US20250295821
2025-09-25
Human necessities
A61K51/082
The patent application details a pharmacological composition designed for the diagnosis and treatment of integrin αvβ3-positive tumors. The composition includes a structurally modified RGD polypeptide coupled with a radionuclide. This formulation can be combined with immunotherapeutic agents and potentially includes a nanoantibody molecular imaging probe. This combination aims to enhance the efficacy of tumor treatment by integrating targeted radiotherapy with immunotherapy.
Integrins, particularly integrin αvβ3, play a critical role in tumor angiogenesis, which is essential for tumor growth and metastasis. The RGD polypeptide specifically binds to integrin αvβ3, making it a valuable tool for targeting tumors. However, challenges such as low tumor uptake and high organ uptake of radiolabeled cyclic RGD peptides have limited their effectiveness as imaging agents. Additionally, combining traditional cancer therapies with immunotherapy has shown potential to overcome resistance and recurrence issues associated with conventional treatments.
Combining targeted radiotherapy with immunotherapy, especially using PD-1 or PD-L1 blockade strategies, can potentially enhance treatment efficacy. Radiotherapy can promote the release of tumor antigens and improve the function and infiltration of effector T cells, providing synergy with immune checkpoint blockade therapy. The invention also suggests using a nanoantibody probe targeting PD-L1 to monitor the tumor microenvironment in real-time, aiding in the development of personalized treatment strategies.
The invention outlines the structure of the modified RGD polypeptide as A-(L)n-RGD polypeptide, where A is a specific structure, L is a linking arm molecule, and n is either 0 or 1. The radionuclide-labelled complex is defined as Nu-BFC-A-(L)n-RGD polypeptide, where Nu represents various radionuclides for diagnostic or therapeutic purposes, and BFC is a bifunctional chelator that facilitates binding with the radionuclide.
The invention encompasses various configurations of the RGD polypeptide and radionuclide complexes, such as 68Ga-DOTA-A-c(RGDfk) or 99mTc-HYNIC-A-3PRGD2. It also acknowledges the potential need for coligands when certain bifunctional chelators are used. These configurations are intended to improve targeting and treatment efficacy in integrin αvβ3-positive tumors while offering flexibility in their application.