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In the trial with mice, tumor cells from patients with colon cancer have been implanted and the disease has remitted
The scientist at the Biomedical Research Institute (IRB) of Barcelona, Eduard Batlle, leads an international consortium that has discovered the MCLA-158 antibody, the first drug candidate targeting cancer stem cells from solid tumors that prevents the spread of cancer and metastasis.
Batlle, head of the IRB Colorectal Cancer laboratory, in collaboration with the Dutch biotechnology company Merus NV, publishes in the journal Nature Cancer the preclinical data that have led to the discovery of MCLA-158 and its mechanism of action on cancer stem cells.
As reported by the IRB in a statement, with the commercial name of Petosemtamab, the MCLA-158 antibody blocks the spread of cancer to other organs and slows the growth of primary tumors in mice in which tumor cells from patients with colon cancer have been implanted.
The research lays the foundation for incorporating the use of organoids into the drug discovery process.
The organoids are patient-derived samples that can be cultured and They reproduce the behavior of the tumor in the laboratory.
Until now, they have explored its usefulness in personalized cancer medicine, but to discover MCLA-158, for the first time they have used a organoid biobank of cancer patients to discriminate among hundreds of new antibodies which of them was most effective and suitable for the majority of patients.
In October 2021, Merus published preliminary data analyzing the antibody's efficacy, based on its ongoing Phase 1 dose expansion clinical trial.
In this clinical trial, the safety, tolerability and antitumor activity of MCLA-158 monotherapy in head and neck squamous cell carcinomas (HNSCC).
On trial, three of seven patients with HNSCC achieved partial remissions, and one of them achieved a complete remission, while in all seven patients there was a tumor reduction.
"We started researching cancer stem cells 15 years ago. The path to get here has been exciting, but also very complex, it has required a large investment of resources and the efforts of many researchers. The medicine of the future begins here," said Batlle.
The antibodies They are proteins that the body produces naturally to recognize infectious agents or altered cells and that can be eliminated by the lymphocytes of the immune system (white blood cells).
The antibody described in this work, Petosemtamab (MCLA-158), is a bispecific antibody that recognizes two different proteins on cancer stem cells, EGFR and LGR5.
EGFR activity promotes uncontrolled cell growth, while LGR5 marks the surface of cancer stem cells, responsible for the expansion of tumors.
As detailed by Batlle, MCLA-158/Petosemtamab degrades the EGFR protein in cancer stem cells that present the LGR5 marker and thus blocks growth and survival pathways in the cells that initiate cancer and expand it.
"This antibody does not interfere with the functioning of healthy stem cells of the body, which are essential for the proper functioning of tissues," according to Batlle.
Preclinical data indicate that the MCLA-158 antibody shows potent growth inhibition of colorectal cancer organoids, blocks the initiation of metastasis and cancer growth in different tumor models, including head and neck, esophagus and stomach. .
To characterize this antibody, they built a biobank with organoids derived from colon cancer patients, organoids from colon cancer metastasis to the liver and organoids from normal non-cancerous tissue.
According to the researchers, incorporating organoids in the initial phases of drug generation (in this case, therapeutic antibodies) allows identify those that are effective for the majority of patients or even for tumors carrying a particular mutation.
Another advantage is the possibility of identifying unwanted side effects of drugs on organs, using organoids from healthy tissue, which has allowed evaluate the harmful effects of the drug on healthy cells and thus eliminate the antibodies with greater toxicity in the earliest phases of the study.
In the coming months, the Merus company plans to publish new data on ongoing clinical trials with Petosemtamab. "We hope that the antitumor activity published in the preliminary data will be confirmed," Batlle confessed.
The Hubrecht Institute, the Sanger Institute, the companies Ocello BV/Crown Bioscience and Xenopat, the Vall d'Hebron Institute of Oncology (VHIO), the Catalan Institute of Oncology (ICO), the Biomedical Research Institute have also participated in this research. from Bellvitge (IDIBELL).
Source: The World
