Anti-SSTR2 antibody-drug conjugate for neuroendocrine tumor therapy

Area of Science:

• Oncology
• Pharmacology
• Immunology

Background:

• Neuroendocrine (NE) tumors are a heterogeneous group of hormone-secreting neoplasms.
• Current treatments for NE tumors, including chemotherapy and radiotherapy, offer limited efficacy.
• There is a critical need for novel therapeutic strategies for NE tumors.

Purpose of the Study:

• To develop an innovative antibody-drug conjugate (ADC) for the effective treatment of NE tumors (NETs).
• To identify and validate somatostatin receptor 2 (SSTR2) as a specific cell surface target on NETs.

Main Methods:

• SSTR2 expression was analyzed in patient-derived NET tissues, normal organs, and NET cell lines.
• A novel monoclonal antibody (mAb) targeting SSTR2 was developed and conjugated with monomethyl auristatin E to create an ADC.
• In vitro assays assessed ADC binding, internalization, payload release, and cytotoxicity against NET cells.
• In vivo studies in a NET xenograft mouse model evaluated the ADC's targeting, pharmacokinetics, safety, and antitumor efficacy.

Main Results:

• SSTR2 was confirmed as an ideal cancer cell surface target with high specificity for NETs.
• The anti-SSTR2 ADC demonstrated potent and specific binding, internalization, and killing of NET cells in vitro.
• In vivo, the anti-SSTR2 ADC exhibited exclusive targeting of NET cells, favorable pharmacokinetics, minimal toxicity, and significant antitumor activity.
• The ADC showed high stability in vivo.

Conclusions:

• The developed anti-SSTR2 antibody-drug conjugate (ADC) is a promising therapeutic candidate for neuroendocrine tumors.
• This targeted approach offers a potentially effective and safe treatment strategy for NETs, addressing the limitations of current therapies.