Bay Area biotech relies on immune-boosting antibodies to fight endpoint-resistant cancers – Endpoints News

The scientist behind the first prostate cancer vaccine, Provenge – a historic celebration, but now a shooting star – has developed a type of antibody-armed – loaded with an immuno -stimulating rather than a cytotoxic payload – to fight against the army-resistant cancers of existing checkpoint inhibitors.

The researcher, Ed Engleman, of Stanford, has relied on his research on dendritic cells – considered "sentinels" of the immune system because they are responsible for inducing immune T cell responses – for develop this immunostimulatory antibody conjugate technology (ISAC), which was unveiled Monday by the exclusive licensee Bolt Therapeutics at the conference of the American Association for Research on Cancer (AACR).

"What Bolt proposed was to wake the dendritic cells in the (tumor) microenvironment, and we were able to do so in a targeted way," said David Dornan, senior vice president of research, in a interview with News on the end points before the conference.

Many patients are refractory to checkpoint inhibitors because of the presence of many immunosuppressive factors in their tumor microenvironment. The researchers have therefore tried to mobilize different molecules to stimulate the immune system, including similar receptor agonists (TLR) – specialized proteins that initiate an immune response to foreign pathogens or, in this case, cells. cancerous.

But the challenge of administering these adjuvants is that they must be administered intratumorally because if they are administered systemically – for example, orally or intravenously – they can become toxic if immune cells are activated throughout the body and the impact is not targeted, Dornan said.

Bolt's ISAC technology is therefore targeted – it combines an adjuvant with a tumor-targeting antibody to deliver that immune agonist directly to the tumor.

This is a logical evolution: Originally, the researchers targeted the tumor with chemotherapy or conjugated antibodies, and then developed the checkpoint inhibitors designed to induce the immune system to attack the tumor, the chief executive said. of Bolt, Grant Yonehiro. "We do both, we target the tumor with our antibodies, but we also activate the immune system in the tumor."

But it's still early. Bolt has so far conducted preclinical studies.

The data suggests that the technology can "reinvigorate the immune system to the extent that if the cancer recurs, you have a repertoire of T cells that can find, start to proliferate and then kill the cancer cells," he said. said Dornan.

"We observe a significant narrowing of the tumor in preclinical models, an immunological memory – the possibility for once to eliminate a tumor, that if the cancer recurs – if we give the mouse the cancer cells, we n & # 39; We have no new administration to administer. therapy – Mouse T cells recognize the tumor and eradicate it. We have used these models in cancers largely refractory to standard therapies. "

With the addition of a cytotoxic load, the duration of the response is the main obstacle – but the addition of an immuno-stimulant can help to overcome this problem, said the leaders. Bolt's preclinical data showed that the ISAC approach arm the body with a repertoire of T cells that, even if the cancer tries to mutate around it, have a chance to fight.

Bolt has several programs in his arsenal, and his main program will likely be developed for breast cancer, gastric cancer and bladder cancer, said Dornan.

Bay Area, which has 30 employees, has already raised $ 72 million and hopes to be in the clinic by 2020. An IPO is also planned. "We are still a bit early for that, but we think there is a lot of potential for an IPO down the line," Yonehiro said.