ICAM1 antibody drug conjugates exert potent antitumor activity in papillary and anaplastic thyroid carcinoma

Area of Science:

• Oncology
• Immunology
• Biotechnology

Background:

• Anaplastic thyroid cancer (ATC) and refractory papillary thyroid carcinoma (PTC) have limited treatment options and poor patient outcomes.
• Intercellular adhesion molecule-1 (ICAM1) has been identified as a potential therapeutic target in these aggressive thyroid cancers.

Purpose of the Study:

• To evaluate ICAM1 as a therapeutic target for ATC and PTC.
• To develop and assess novel ICAM1-directed antibody-drug conjugates (ADCs) for efficacy.
• To explore non-invasive methods for quantifying ICAM1 expression in thyroid tumors.

Main Methods:

• Bioinformatic expression analyses and immunohistochemistry staining to identify ICAM1 expression.
• Design and engineering of two ICAM1-directed ADCs: I1-MMAE and I1-DXd.
• In vitro assessment of ADCs on human ATC and PTC cell lines and in vivo evaluation in xenograft models.
• Exploration of magnetic resonance imaging (MRI) for non-invasive ICAM1 quantification.

Main Results:

• ICAM1 was confirmed as a highly attractive target for ATC and PTC.
• Both I1-MMAE and I1-DXd demonstrated potent and selective ablation of ATC and PTC cell lines in vitro.
• ADCs I1-MMAE and I1-DXd achieved significant tumor regression in preclinical xenograft models.
• MRI was explored as a viable method for non-invasive ICAM1 biomarker detection.

Conclusions:

• The developed ICAM1-directed ADCs (I1-MMAE and I1-DXd) show significant therapeutic potential for advanced thyroid cancers.
• These findings provide a strong rationale for the further clinical development of I1-MMAE and I1-DXd.
• Precision medicine approaches, including non-invasive biomarker mapping, can enhance treatment strategies for PTC and ATC.