A novel anti-CD146 antibody specifically targets cancer cells by internalizing the molecule

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• CD146 is an adhesion molecule overexpressed on various human tumors, including melanoma, kidney, pancreas, and breast cancers.
• CD146 is also present on vascular endothelial and smooth muscle cells, posing a challenge for targeted therapies.
• Developing an antibody that selectively targets tumor CD146 is crucial for effective cancer treatment without systemic side effects.

Purpose of the Study:

• To generate and characterize a monoclonal antibody (mAb) that specifically recognizes CD146 on cancer cells.
• To evaluate the diagnostic potential of this antibody for detecting CD146-positive tumors and circulating tumor microparticles.
• To assess the therapeutic efficacy of the antibody in reducing the growth of CD146-positive tumors.

Main Methods:

• Generation of antibodies against the extracellular domain of CD146 expressed in cancer cells.
• Selection of an antibody (TsCD146 mAb) with high specificity for tumor CD146.
• Validation of TsCD146 mAb in human tumor biopsies and a murine xenograft model using PET imaging.
• Detection of CD146-positive cancer microparticles in patient plasma.
• Assessment of therapeutic effects in vivo, including tumor growth inhibition, proliferation, and apoptosis assays.

Main Results:

• TsCD146 mAb specifically recognizes tumor CD146, distinguishing it from normal cell-expressed CD146.
• The antibody successfully detected CD146-positive tumors in human biopsies and in vivo via PET imaging.
• TsCD146 mAb identified CD146-positive cancer microparticles in the plasma of cancer patients.
• Treatment with TsCD146 mAb significantly reduced the growth of CD146-positive human cancer xenografts in mice.
• The therapeutic effect was attributed to decreased cancer cell proliferation and increased apoptosis following antibody-mediated CD146 internalization.

Conclusions:

• TsCD146 mAb is a promising diagnostic and therapeutic agent for CD146-positive malignancies.
• The antibody's ability to target tumor-specific CD146 offers a strategy for personalized medicine approaches.
• This targeted antibody has potential applications in imaging, early detection, and treatment of various cancers.