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Double Whammy Antibody Draws T Cells to Cancerous Tumors

T cell-engaging bispecific antibodies (biAbs) pose a promising approach for cancer immunotherapy, and many bispecific formats are created for retargeting cytolytic T cells toward tumor cells.

To explore the therapeutic utility of T cell-engaging biAbs targeting the receptor tyrosine kinase ROR1, that can be expressed by tumor cells of different hematologic and solid malignancies, scientists at the The Scripps Research Institute in Florida have now undertaken a new investigation.

At the laboratory of biochemist and immunologist Christoph Rader, PhD, associate professor at The Scripps Research Institute at Florida, scientists have engineered a new kind of anti inflammatory antibody, one meant to improve character’s cancer-fighting strategies by bringing killer T cells directly into cancer cells coated with a distinguishing protein.

Dubbed”T-cell engaging bi-specific antibodies,” those cancer combatants attack cancerous cells but leave healthy cells unaffected.  That is thanks to their particular targeting system, which zeroes in on a protein found in the face of various kinds of cancer cells known as ROR1, and thanks to their ability for binding together with T cells, the huge guns of their immune system.

Once the T cells are recruited and activated, they release cytotoxic molecules that penetrate the target cells and kill them

,” Rader says. “Natural antibodies can’t do this. You have to engineer them in a bi-specific fashion to do this.”

If you look at ROR1 expression in breast cancer, you see that the patients who are HER2 negative are often ROR1 positive,” Rader says. “These breast cancer patients might benefit.”

Antibodies are proteins produced from white blood cells to strike certain goals like viruses, cancers and bacteria.  A bi-specific antibody is a Y-shaped immune variable designed to bind with a particular disease goal, and to bring killer T cells, a sort of white blood cell that destroys infected or harmful cells.

ROR1 is a great goal for a clever cancer-fighting system, Rader says, as it’s found only in older cells that are cancerous.  Rader first found ROR1’s action in leukemia a decade ago while working in the National Cancer Institute.

ROR1 is expressed during embryogenesis, and then it is tightly down-regulated after birth. It later reappears in both blood cancers and solid malignancies,” Rader says. It has been found on malignant cells including lung, breast, ovarian and blood-based cancers, Rader says. “One of the most unique aspects of this bi-specific antibody is that it can work in so many different cancer indications,” Rader says.

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