The Antibody–Drug Conjugate Target Landscape

Data-driven prioritization of clinically available antibody–drug conjugates directed against targets across a broad range of tumour types

The researchers from the Department of Medical Oncology, University Medical Centre Groningen, Groningen, The Netherlands led by Dr Rudolf Fehrmann published in December issue of the Annals of Oncology an analysis that provides a data-driven prioritization of clinically available antibody–drug conjugates (ADCs) directed against 59 targets across 60 tumour (sub)types.

The ADCs consist of an antibody designed against a specific target at the cell membrane linked with a cytotoxic agent and represent an emerging class of therapeutics in oncology.

The authors wrote in study background that because ADC tumour cell targets do not have to be drivers of tumour growth, they are potentially relevant for a wide range of tumours currently lacking clear oncogenic drivers. Therefore, their aim was to define the landscape of ADC targets in a broad range of tumours.

The authors searched on PubMed and ClinicalTrials.gov for ADCs that are or were evaluated in clinical trials. Gene expression profiles of 18 055 patient-derived tumour samples representing 60 tumour (sub)types and 3520 healthy tissue samples were collected from the public domain. Next, they applied functional genomic mRNA-profiling to predict per tumour type the overexpression rate at the protein level of ADC targets with healthy tissue samples as a reference.

The study team identified 87 ADCs directed against 59 unique targets.

A predicted overexpression rate of ≥ 10% of samples for multiple ADC targets was observed for high-incidence tumour types like breast cancer (n = 31 with n= 23 in triple negative breast cancer), colorectal cancer (n= 18), lung adenocarcinoma (n= 18), squamous cell lung cancer (n= 16) and prostate cancer (n= 5).

In rare tumour types the researchers observed, amongst others, a predicted overexpression rate of 55% of samples for CD22 and 55% for ENPP3 in adrenocortical carcinomas, 81% for CD74 and 81% for FGFR3 in osteosarcomas, and 95% for c-MET in uveal melanomas.

The authors concluded that this comprehensive ADC target landscape can guide clinicians and drug developers which ADC is of potential interest for further evaluation in which tumour (sub)type. 

Reference

Moek KL, de Groot DJA, de Vries EGE, Fehrmann RSN. The antibody–drug conjugate target landscape across a broad range of tumour types. Annals of Oncology 2017; 28(12):3083-3091.