Preclinical Evaluation of PTK7-Targeted Radionuclide Therapy

Area of Science:

• Oncology
• Radiochemistry
• Immunotherapy

Background:

• Protein tyrosine kinase 7 (PTK7) is a receptor expressed in tumor-initiating cells and various malignancies, including ovarian cancer.
• PTK7 has been investigated for antibody-drug conjugates, but its potential for targeted radionuclide therapy remains unexplored.

Purpose of the Study:

• To investigate the potential of a PTK7-targeting antibody (OI-1) for targeted radionuclide therapy in ovarian cancer.
• To develop and evaluate antibody-radionuclide conjugates (ARCs) based on the OI-1 antibody.

Main Methods:

• Development of a murine monoclonal antibody (mOI-1) against PTK7 using hybridoma technology, followed by chimeric version (chOI-1) generation.
• Cell-based screening, flow cytometry, and surface plasmon resonance to confirm PTK7 as the target.
• In vitro and in vivo studies using ovarian cancer cell lines and xenograft mouse models with radiolabeled OI-1 (177Lu-DOTA-mOI-1 and 212Pb-TCMC-chOI-1).

Main Results:

• PTK7 expression was confirmed in ovarian cancer tissues, and OI-1 showed specific binding and internalization in SKOV-3-luc cells.
• Biodistribution studies with 177Lu-DOTA-mOI-1 revealed high tumor uptake and retention in xenograft mice.
• Therapeutic efficacy studies with 212Pb-TCMC-chOI-1 demonstrated significant inhibition of intraperitoneal ovarian tumor growth.

Conclusions:

• The OI-1 antibody is a promising candidate for developing targeted radionuclide therapies against PTK7-expressing cancers.
• This study provides the first preclinical evidence for a PTK7-targeting antibody-radionuclide conjugate in ovarian cancer models.
• Further investigation of OI-1 based ARCs is warranted for clinical translation in ovarian and other PTK7-positive malignancies.