Newly identified molecule promises to transform cancer immunotherapy

In a breakthrough discovery, a joint research team made of scientists from the University of Lisbon at Tel Aviv University (TAU) has identified and synthesized a small molecule that helps fight cancer. The discovery could make immunotherapy available to all cancer patients.

The results of the study titled “Therapeutic targeting of PD-1/PD-L1 blockade by novel small-molecule inhibitors recruits cytotoxic T cells into solid tumor microenvironment” were published in open access, peer-reviewed the Journal for ImmunoTherapy of Cancer.

The head of the Center for Cancer Biology Research and of the Laboratory for Cancer Research and Nanomedicine at TAU’s Sackler Faculty of Medicine, Prof. Ronit Sachi-Fainaro, led the international research team along with Prof. Helena Florindo and Prof. Rita Guedes from the Research Institute for Medicines at the Faculty of Pharmacy at the University of Lisbon.

As the study abstract says, researchers have identified “a new promising family of small-molecule candidates that regulate the PD-L1/PD-1 signaling pathway, promoting an extensive infiltration of effector CD8 T cells to the tumor microenvironment.”

Cancer immunotherapy: molecule vs antibody treatment

Just like PD-L1/PD-1 inhibitors, these novel small molecules “can stimulate human adaptive immune responses.” But unlike them, molecules “enabled an extensive infiltration of T lymphocytes into three-dimensional solid tumor models, and the recruitment of cytotoxic T lymphocytes to the tumor microenvironment in vivo, unveiling a unique potential to transform cancer immunotherapy.”

“If there are fewer blood vessels in a particular area of the tumor, the antibody will not be able to get inside. The small molecule, on the other hand, diffuses and is therefore not entirely dependent on the tumor’s blood vessels or on its hyperpermeability,” explains Prof. Sachi-Fainaro.

However, the novel molecule is a more accessible and effective alternative for treating a range of cancers to monoclonal antibodies that were so far the only ones approved for clinical use as PD-1/PD-L1 inhibitors.

“I believe that in the future, the small molecule will be commercially available and will make immunotherapy affordable for cancer patients,” says Prof. Sachi-Fainaro as quoted by The Jerusalem Post.

As he points out, “the antibody is a biological molecule that demands a complex infrastructure and considerable funds to produce,” while the new molecule was synthesized “with simple equipment in a short time and at a fraction of the cost.”

“Another advantage of the small molecule is that patients will probably be able to take it orally at home, without the need for IV administration in the hospital,” Prof. Sachi-Fainaro emphasized.

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