EV20/Omomyc: A novel dual MYC/HER3 targeting immunoconjugate
MYC is one of the most important therapeutic targets in human cancer. Many attempts have been made to develop small molecules that could be used to curb its activity in patients, but most failed to identify a suitable direct inhibitor. After years of preclinical characterization, a tissue-penetrating peptide MYC inhibitor, called Omomyc, has been recently successfully used in a Phase I dose escalation study in late-stage, all-comers solid tumour patients. The study showed drug safety and positive signs of clinical activity, prompting the beginning of a new Phase Ib combination study currently ongoing in metastatic pancreatic adenocarcinoma patients. In this manuscript, we have explored the possibility to improve Omomyc targeting to specific cancer subtypes by linking it to a therapeutic antibody. The new immunoconjugate, called EV20/Omomyc, was developed by linking a humanised anti-HER3 antibody, named EV20, to Omomyc using a bifunctional linker. EV20/Omomyc shows antigen-dependent penetrating activity and therapeutic efficacy in a metastatic model of neuroblastoma. This study suggests that directing Omomyc into specific cell types using antibodies recognising tumour antigens could improve its therapeutic activity in specific indications, like in the paediatric setting.
Authors
- Marie-Ève Beaulieu (ORCID: https://orcid.org/0000-0001-5224-8436)
- Emily Capone (ORCID: https://orcid.org/0000-0001-6719-2535)
- Vincenzo De Laurenzi (ORCID: https://orcid.org/0000-0002-7506-1743)
- Francesco Giansanti (ORCID: https://orcid.org/0000-0002-8335-3412)
- Martina Morini (ORCID: https://orcid.org/0000-0003-2569-4515)
- Sara Ponziani
- Katia Mazzocco (ORCID: https://orcid.org/0000-0002-6599-5681)
- Stefano Iacobelli
- Alessia Lamolinara (ORCID: https://orcid.org/0000-0002-7421-4509)
- Manuela Iezzi (ORCID: https://orcid.org/0000-0002-6296-6498)
- Laura Soucek (ORCID: https://orcid.org/0000-0002-4750-7971)
- Arturo Sala (ORCID: https://orcid.org/0000-0002-2841-7866)
- Rossano Lattanzio (ORCID: https://orcid.org/0000-0001-9803-4476)
- Jonathan R. Whitfield (ORCID: https://orcid.org/0000-0002-4925-7283)
- Rodolfo Ippoliti (ORCID: https://orcid.org/0000-0003-0652-3470)
- Sandra Bibbò (ORCID: https://orcid.org/0000-0001-6007-9222)
- Gianluca Sala
- Giulio Lovato
Institutions
- Institució Catalana de Recerca i Estudis Avançats (ES)
- University of L'Aquila (IT)
- Istituto Giannina Gaslini (IT)
- University of Chieti-Pescara (IT)
- FC Barcelona (ES)
- Vall d'Hebron Institute of Oncology (ES)
- Brunel University of London (GB)
Publication Details
- Journal
- Journal of Controlled Release
- Published
- 2024-08-15
- DOI
- https://doi.org/10.1016/j.jconrel.2024.08.009
- Citations
- 5
- Primary Topic
- Neuroblastoma Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 1.85
Funders
- Fundación Cellex
- Ministerio de Ciencia, Innovación y Universidades
- Centres de Recerca de Catalunya
- Generalitat de Catalunya
- Associazione Italiana per la Ricerca sul Cancro