Therapeutic Targeting Tongue Squamous Cell Carcinoma via ICAM1 Antibody-Drug Conjugates in Preclinical Models

Abstract

To date, the treatment options for metastatic and recurrent tongue squamous cell carcinoma (TSCC) remain limited due to the lack of effective drug targets and therapeutics. Here the identification of ICAM1 is reported as a TSCC target candidate for the development of antibody-drug conjugate (ADC), an emerging class of targeted therapeutics. An unbiased and quantitative screening of a panel of 69 TSCC cell surface antigens is first performed that identifies ICAM1 as the most abundant hit. The overexpression level of ICAM1 is validated in 26 TSCC clinical specimens and four cell lines along with genomic information of 127 TSCC patients from the TCGA database. Based on this new target, the anti-TSCC efficacy of ICAM1-targeted ADCs featuring two payloads is evaluated of different mechanisms of action: MMAE and DXd. Both ADCs selectively and potently ablate TSCC tumors in the established SAS cell line and patient-derived xenograft (PDX) models. The findings strongly support ICAM1 as a promising ADC target candidate for TSCC therapy.