LAUSR

Conventional cancer chemotherapy relies on the use of cytotoxic drugs which are not designed and capable of selective accumulation to neoplastic lesions. The conjugation to tumour-targeting delivery vehicles has been proposed as a strategy to enhance the therapeutic index of potent cytotoxic drugs. To date, fifteen Antibody-Drug Conjugate products have received marketing approval for the treatment of solid and liquid human malignancies. We present an in vivo comparative evaluation of ADCs against products based on small organic delivery vehicles (Small Molecule-Drug Conjugates, or SMDCs) or on tumour-targeting peptides (Peptide-Drug Conjugates, or PDCs). All products are designed to target and to be activated by Fibroblast Activation Protein in the tumour microenvironment. Our results reveal that both targeted ADC and SMDC products mediate potent anti-cancer activity and complete tumour remission in a FAP-positive preclinical murine model of cancer, when administered at the same molar dose. Non-targeted albumin and antibody conjugates included in our comparative studies delayed tumour growth but presented suboptimal anti-cancer efficacy in the same cancer model. Our results indicate that both FAP-targeted ADCs and SMDCs are promising product candidates for the treatment of multiple human malignancies. Citation Format: Aureliano Zana, Claudia Puig Moreno, Ettore Gilardoni, Dario Neri, Samuele Cazzamalli. FAP-targeted non-internalising drug conjugates: A comparative evaluation between small molecules, antibodies and peptides [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1988.