Anti-PRL-3 Monoclonal Antibody inhibits the Growth and Metastasis of colorectal adenocarcinoma

Abstract

Background: Colon cancer is the one of leading causes of cancer-related death. Chemotherapy, radiotherapy and immunotherapy will be the mainstream in inoperable advanced cancer in clinics. Precision treatment is still lack in colon cancer. Materials and Methods: We developed a series of mAbs targeting PRL-3 through different types of immunogens. The binding domains of mAbs were identified through the ELISA and Western blotting experiments. The antitumor activity of mAbs was verified by cell proliferation, migration and invasion experiments. Xenograft subcutaneous and metastatic models and patient derived Xenograft (PDX) model were established. Results: mAb 12G12 targeting 77-120AA exhibited inhibition in migration and invasion experiments. 12G12 inhibited the migration of multiple types of cancer cells, including colon cancer, gastric cancer, esophagus cancer, liver cancer, lung cancer and pancreatic cancer cells. 12G12 decreased the tumor growth and metastasis in Xenograft subcutaneous and metastatic tumor model, respectively. The antitumor activity of mAb 12G12 was also confirmed in PDX model of gastric cancer. PRL-3 interacted with Golgi protein TMED10. Knockdown of TMED10 expression attenuated the cell migration triggered by purified GST-PRL-3 protein. Conclusion: Our results confirmed the antitumor activity of mAb 12G12 in colorectal adenocarcinoma and provided a new potential targeted therapy of colon cancer.

Protein Tyrosine Phosphatase PRL-3: A Key Player in Cancer Signaling

“…In 2019, PRL-3-zumab, a First-in-Class humanized antibody drug, demonstrated the ability to bind to the surface of PRL-3 in a manner consistent with the classical antibody-dependent cell-mediated cytotoxicity (ADCC) action or antibody-dependent cell phagocytic tumor elimination pathway [ 140 , 156 ]. Subsequently, PRL-3-zumab has been proven to reduce tumor relapse in the ‘tumor removal’ animal model [ 142 ] and has been confirmed to have anti-tumor activity in the PDX model [ 157 ]. As a therapeutic mAb, PRL-3-zumab has demonstrated a strong safety profile in clinical trials, presenting a promising avenue for targeted therapy against PRL-3 [ 158 ].…”