Immunotherapy Homes In On Multiple Myeloma

Scientists in Japan have identified a monoclonal antibody that can be used in CAR-T therapy against multiple myeloma.

AsianScientist (Dec. 7, 2017) – A team of researchers in Japan have developed a T cell therapy that specifically targets multiple myeloma cancer cells. They published their work in Nature Medicine.

In recent decades, monoclonal antibody-based treatment of cancer has been established as one of the most successful therapeutic strategies for both solid tumors and blood cancers. Monoclonal antibodies (mAb), as the name implies, are antibodies that are made by clones derived from a single parent cell, and therefore share identical amino acid sequences.

One of the leading technologies to emerge in mAb-based treatment is chimeric antigen receptor T-cell (CAR-T) therapy. CAR-T cells are produced by combining the gene for an antibody that recognizes a tumor antigen with the gene for a receptor that resides on the surface of the T-cells; insert this new gene into a T-cell and it will be precisely targeted at the tumor.

In this study, the researchers at Osaka University screened more than 10,000 mAb clones and identified a mAb that specifically recognizes multiple myeloma (MM) cells, calling it MMG49. MMG49 binds to a subset of integrin β7, which are cell-surface proteins that allow cells to attach to surfaces.

“We applied this strategy to identify novel therapeutic targets for multiple myeloma, a cancer that forms in a type of white blood cell called a plasma cell,” explained study lead author Dr. Naoki Hosen of Osaka University.

MMG49 reacted to MM cells, but not other bone marrow cell types in MM patient samples. This prompted the researchers to design a CAR-T cell that incorporates a fragment derived from MMG49. The resulting MMG49 CAR-T cell was found to have anti-MM effects without damaging normal blood cells.

“Our results demonstrate that the active conformer of integrin β7 can serve as an immunotherapeutic target against MM, even though the expression of the protein itself is not specific to MM,” said study coauthor Dr. Yukiko Matsunaga of the University of Tokyo. “Therefore, it is highly plausible that there are other cancer immunotherapeutic targets that have yet to be identified among the many cell-surface proteins that undergo conformational changes, even if the expression of the proteins themselves is not cancer-specific.”

The article can be found at: Hosen et al. (2017) The Activated Conformation of Integrin β7 is a Novel Multiple Myeloma–specific Target for CAR T Cell Therapy.


Source: Osaka University.
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