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Gilead and Tango to develop novel immuno-oncology drugs

The partners will look for targets that help tumor cells hide from the immune system

by Lisa M. Jarvis
October 31, 2018 | A version of this story appeared in Volume 96, Issue 44

A schematic explaining the concept of synthetic lethality.
Credit: AstraZeneca/C&EN
Synthetic lethality exploits the concept that cancer cells that have lost key gene functions are dependent on alternative pathways.

Gilead Sciences will pay $50 million to Tango Therapeutics as part of a deal to identify novel immuno-oncology drug targets. The companies will jointly work on finding five new targets that help tumor cells stave off an immune attack.

The field of cancer immunology has blossomed thanks to the discovery of a class of drugs called checkpoint inhibitors. The drugs—six of which are now on the market in the U.S.—work by blocking proteins displayed on the surface of T cells. When that happens, the immune cells are empowered to see and attack tumor cells.

Gilead and Tango, in contrast, are interested in finding promising immuno-oncology targets on cancer cells themselves. “There’s been great success in activating the immune system to help kill tumors, but if you think about it, tumors are intrinsically programmed to avoid the immune system,” says Tango CEO Barbara Weber.

Photo of Tango Therapeutics' CEO Barbara Weber.
Credit: Tango Therapeutics
Tango CEO Barbara Weber

They do that by sending out signals that keep immune cells at bay. The notion that tumor cells can change their microenvironment this way was until recently quite controversial, notes University of Chicago Medicine’s Randy F. Sweis, who studies how alterations in tumor gene function affect the tumor immune microenvironment. But it has become increasingly accepted that tumor-level mutations can explain why some cancer patients don’t benefit from the currently approved cancer immunotherapies.

“If you turn on these specific genes in tumors, they can actively exclude T cells from the tumor microenvironment,” which in turn renders checkpoint inhibitors ineffective, Sweis says.

Tango is using its CRISPR-based screening platform to uncover targets that can be broached by small molecules. Often, tumor-level mutations cause a loss of function in a gene, leaving no protein for small molecules to attack. But Tango is focused on synthetic lethality, the notion that cancer cells can survive one, but not two, critical gene losses. Tango is looking for a second gene that, if targeted with a small molecule, will reverse the tumor cell signaling that is driving away immune cells.

Weber calls the deal an important milestone for Tango. Once Gilead chooses a drug target, it will do its own discovery and development work; Tango will receive milestones and can later opt to jointly develop two of the five drug candidates included in the pact. The set-up means Tango can support its internal research, which Weber says is on track to yield two compounds ready for human studies by late 2020.


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