Scientists from an international consortium led by IRB Barcelona and the Dutch company Merus N.V., in which researchers from IDIBELL and the Catalan Institute of Oncology have participated, present the preclinical data leading to the discovery of MCLA-158 and its mechanism of action on cancer stem cells.
Under the name of Petosemtamab, the MCLA-158 antibody blocks metastases and slows the growth of primary tumors in experimental cancer models.
In the study, published in the journal Nature Cancer, the researchers from IDIBELL and the Catalan Institute of Oncology, Dr. Ramón Salazar, Dr. Cristina Santos, and Dr. Alberto Villanueva, together with the spin-off that emerged from IDIBELL Xenopat, have demonstrated the effectiveness of MCLA-158 in the post-implantation metastasis inhibition of tumor cells from colon cancer patients in mice.
On the other hand, for the first time, a biobank of organoids from cancer patients was used to discriminate among hundreds of new antibodies the most effective and suitable.
There is currently a phase 1 clinical trial underway evaluating the safety, tolerability, and antitumor activity of MCLA-158. Preliminary results in head and neck squamous cell carcinomas (HNSCC) show encouraging results.
MCLA-158: an antibody with two action fronts
The antibody described in this work, Petosemtamab (“Peto”, MCLA-158: LGR5 x EGFR Biclonics®), is a bispecific antibody that recognizes two different proteins on the surface of cancer stem cells, which are EGFR and the LGR5. EGFR activity promotes uncontrolled cell growth, while LGR5 marks the surface of cancer stem cells.
Specifically, MCLA-158/ Petosemtamab degrades the EGFR protein in cancer stem cells that display the LGR5 marker. It blocks growth and survival pathways in cells that start and spread cancer. This antibody, however, does not interfere with the function of the body’s healthy stem cells, which are essential for proper tissue function.
The preclinical research published in Nature Cancer includes work carried out within the framework of the EU-funded suppresSTEM consortium and with the collaborative work of various international research institutions; IRB Barcelona, the Hubrecht Institute, and the Sanger Institute, and the companies –Merus NV and Ocello BV/Crown Bioscience. The Vall d’Hebron Institute of Oncology (VHIO) also collaborated on this publication.
Original piece by IRB Barcelona: link
The Bellvitge Biomedical Research Institute (IDIBELL) is a biomedical research center created in 2004. It is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.
IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).