Scientists identify an antibody that manages to stop cancer metastasis

Spanish scientists have discovered the MCLA-158 antibody a drug candidate targeting cancer stem cells in tumors that prevents cancer spread and metastasis. The finding has been published in the journal Nature Cancer.

Under the trade name of Petosemtamab this drug blocked the expansion to other organs (metastasis) and slowed down the growth of primary tumors in mice to which tumor cells from patients with colon cancer were implanted, indicated a statement from the Barcelona Institute for Research in Biomedicine (IRB).

The research also lays the groundwork for incorporating the use of organoids into the drug discovery process. These are patient samples that can be cultured and that reproduce the behavior of the tumor in the laboratory.

The researchers discovered MLCA-158 when they used a biobank of organoids from cancer patients to discriminate among hundreds of new antibodies to the one that was most effective and suitable for the most.

During preliminary trials testing its efficacy, safety, and tolerability, three of seven people with HNSCC achieved partial remissions. One of them obtained a complete remission, while in all seven there was a reduction of the tumor.

“We started researching cancer stem cells 15 years ago. The road 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 starts here”, said Batlle.

Antibodies 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 one described in this work, Petosemtamab (MCLA-158), is a bispecific one that recognizes two different proteins in cancer stem cells.

The first (called EGFR) favors the uncontrolled growth of cells, while the second (LGR5) marks the surface of cancer stem cells, responsible for the expansion of tumors.

According to Eduard Batlle, Petosemtamab degrades the EGFR protein in cancer stem cells that present the LGR5 marker and thus blocks the growth and survival pathways in which cancer starts and spreads.

“It does not interfere with the functioning of the body’s healthy stem cells, which are essential for the proper functioning of tissues,” Batlle said.

Preclinical data indicate that the MCLA-158 antibody exhibits potent growth inhibition of colorectal cancer organoids, blocks the initiation of metastasis and cancer growth in different tumor models, including head, neck, esophagus, and stomach. .

To characterize it, they built a biobank with organoids derived from colon cancer patients 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) makes it possible to identify those that are effective for the majority of patients or even for tumors that carry a particular mutation.

Another advantage is the possibility of determining unwanted secondary effects of drugs on organs by using organoids from healthy tissue, which made it possible to assess the harmful effects of the drug on healthy cells and thus eliminate antibodies with greater toxicity in the more toxic phases. early in the study.

“We hope that the antitumor activity published in the preliminary data will be confirmed,” Batlle confessed.

Source-larepublica.pe