An international consortium led by Eduard Batlle, a scientist at the Institute for Research in Biomedicine (IRB) in Barcelona, discovered the MCLA-158 antibody, the first drug candidate targeting cancer stem cells from solid tumors that prevents cancer spread and metastasis.
Batlle, head of the IRB’s Colorectal Cancer laboratory, in collaboration with the Dutch biotechnology company Merus NV, published in the journal ‘Nature Cancer’ the preclinical data that led to the discovery of MCLA-158 and its mechanism of action on stem cells of cancer.
As reported by the IRB in a statement, under the trade name Petosemtamab, the MCLA-158 antibody blocks the spread of cancer to other organs and slows the growth of primary tumors in mice that have been implanted with tumor cells from patients with breast cancer. colon.
The investigation also lays the groundwork for incorporating the use of organoids into the drug discovery process.
Remissions in human patients
The organoids they are samples derived from patients that can be cultured and that reproduce the behavior of the tumor in the laboratory.
Until now, they were exploring its usefulness in personalized cancer medicine, but to discover the MCLA-158, for the first time they used a biobank of organoids of cancer patients to discriminate among hundreds of new antibodies which one was most effective and suitable for the majority of patients.
In October 2021, Merus published preliminary data on the analysis of the efficacy of the antibody, based on its ongoing phase 1 dose expansion clinical trial.
This clinical trial investigates the safety, tolerability and antitumor activity of the monotherapy with MCLA-158 in head and neck squamous cell carcinomas (HNSCC).
In the trial, three of seven patients with HNSCC they achieved partial remissions, and one of them achieved a complete remission, while in all seven patients there was a reduction of the tumor.
Healthy stem cells, safe
The antibody described in this work, the petosemtamab (MCLA-158), is an antibody bispecific that recognizes two distinct proteins in cancer stem cells, the EGFR and the LGR5.
“This antibody also does not interfere with the functioning of the body’s healthy stem cells, which are essential for the proper functioning of the tissues,” according to batlle.
The data preclinical indicate that the antibody MCLA-158 shows potent growth inhibition of organoids of colorectal cancer, blocks the initiation of metastasis and cancer growth in different tumor models, including head and neck, esophagus, and stomach.
The Institute also participated in this investigation. hubrechtthe Institute Sangerthe companies ocello BV/Crown Bioscience Y Xenopaththe valley d’Hebron Institute of Oncology (VHIO), the Catalan Institute of Oncology (ICO), the Research Institute biomedical of Bellvitge (IDIBELL).