New technique improves T cell-based immunotherapies for solid tumors

Good news! Cancer is history (soon)!

"Scientists from Scripps Research have enhanced an existing immunotherapy by removing the sugar coating surrounding solid tumors—such as in melanoma, breast, and prostate cancer—so T cells can more effectively kill tumor cells.  ... that this tweak allows T cells to get closer to their targets, which dramatically improves T-cell killing of tumor cells in mouse models.

Compared to blood tumors, solid tumors are resistant to treatment because they build a physical fort around themselves to block immune cells from entering and attacking. Part of this fort is made up of layers of sugar molecules, the outermost of which is a substance called sialic acid. To remove this sialic acid barrier, the research team fused the enzyme sialidase onto cancer therapy agents called bispecific T-cell engager (BiTE) molecules. These molecules typically work by activating a patient’s own T cells against the cancer. ..."

From the abstract:

"Bispecific T-cell engagers (BiTEs) bring together tumour cells and cytotoxic T cells by binding to specific cell-surface tumour antigens and T-cell receptors, and have been clinically successful for the treatment of B-cell malignancies. Here we show that a BiTE–sialidase fusion protein enhances the susceptibility of solid tumours to BiTE-mediated cytolysis of tumour cells via targeted desialylation—that is, the removal of terminal sialic acid residues on glycans—at the BiTE-induced T-cell–tumour-cell interface. In xenograft and syngeneic mouse models of leukaemia and of melanoma and breast cancer, and compared with the parental BiTE molecules, targeted desialylation via the BiTE–sialidase fusion proteins enhanced the formation of immunological synapses, T-cell activation and T-cell-mediated tumour-cell cytolysis in the presence of the target antigen. The targeted desialylation of tumour cells may enhance the potency of therapies relying on T-cell engagers."

New technique improves T cell-based immunotherapies for solid tumors | Scripps Research Scripps Research scientists help T cells more effectively kill solid tumors cells in vitro and in mice by tweaking an existing cancer immunotherapy.

Targeted desialylation and cytolysis of tumour cells by fusing a sialidase to a bispecific T-cell engager (no public access)

The Scripps Research team fused the enzyme sialidase onto bispecific T-cell engager (BiTE) molecules, helping break down the cancer cells’ outer barriers and thereby activating T cells against the cancer.