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New approaches to treating cancer with off-the-shelf immune-stimulating bispecific antibodies - FierceBiotech

New approaches to treating cancer with off-the-shelf immune-stimulating bispecific antibodies - FierceBiotech

New approaches to treating cancer with off-the-shelf immune-stimulating bispecific antibodies - FierceBiotech
Mar 01, 2021 54 secs

The Hopkins researchers designed a bispecific antibody that could target the mutant p53 protein without interfering with intact p53 in normal cells, they explained in the journal Science.

Even when the p53 target was present at “extremely low” levels on the surface of the tumor cells, the researchers wrote, the bispecific antibody was still able to activate T cells to fight the cancer.

The researchers developed mutation-associated neoantigen-directed antibodies (MANAbodies) and then grafted them onto a bispecific antibody that engages T cells.

They tested the resulting bispecific antibody in human cell lines from patients with lung and pancreatic cancer, demonstrating that it could destroy tumor cells with low levels of mutated RAS, while leaving cells with normal RAS alone.

So they designed bispecific antibodies to target either of two specific regions that are likely to be present on malignant T cells, TRBV5-5 or TRBV12.

In cell lines from patients and mouse models of leukemia and lymphoma, the bispecific antibodies targeted and killed the cancer-driving T cells without affecting healthy T cells, and the cancer regressed, the researchers reported in Science Translational Medicine.

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