Using herpes virus vectors, Paul Peter Tak and Carl June team up to solve the CAR-T solid tumor challenge

Paul Peter Tak’s oncolytic virus startup is jumping head-first into a new partnership, looking to tackle solid tumor CAR-Ts.

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来源: Endpts

Carl June

Candel Therapeutics is joining forces with Carl June’s lab at the University of Pennsylvania to see if the herpes virus can boost the effectiveness of CAR-T therapies in solid tumors, the biotech announced Wednesday morning. No financial terms were disclosed, and both parties will retain their respective intellectual property rights.

“We’ve done this work in stealth mode during the last two years,” Candel CEO Paul Peter Tak tells Endpoints News. “And today, we start to unveil what we have been doing through this partnership with the University of Pennsylvania, who are world leaders in the development of CAR-T cells.”

CAR-Ts, though a relatively recent invention, have proven highly effective in treating blood cancers such as leukemias and lymphomas. The FDA has approved six CAR-T therapies in the last five years, and June himself previously said the treatments have surprised even him: “We did not think that this would be a curative therapy at all in 2010,” he told reporters in February.

Replicating those successes in solid tumors, however, has been much more challenging. The CAR-T’s method of administration — removing a patient’s T cells, reengineering them to target tumor antigens to jumpstart the immune system and infusing them back into patients — faces more obstacles in solid tumors, with tumor microenvironments at the forefront.

Wednesday’s deal will center around whether the herpes simplex virus (HSV) vector can help CAR-Ts penetrate those microenvironments, which typically consist of blood vessels and tissues that sustain the tumors and help them evade immune detection. It will focus entirely on discovery work and last for three years, Tak said.

The research itself comes from a new platform Tak said he has been developing at Candel since he joined in December 2020. Spearheaded by the small January 2020 acquisition of PeriphaGen, the platform aims to engineer the transgenes contained within the HSV vector, inject the treatment directly into tumors to break down the microenvironment and then administer the CAR-T therapy.

HSV appealed more than oncolytic viruses such as adenoviruses for this partnership, Tak said, because research has hinted they may be better retained at the tumor sites, allowing for greater CAR-T cell activity.

“The beauty of HSV is that it has a large DNA capacity,” Tak said. “So you can insert, for example, five genes all into one vector. And if you inject it into the specific tumor, let’s say pancreatic cancer, you can start to modulate the tumor microenvironment in such a way that CAR-T cells can get into the tumor.”

Tak has a long history of helping steer new approaches in well-established pathways, having led immunoinflammation R&D at GSK and worked as a partner at Flagship. Whereas the early iterations of oncolytic virus therapies fell short of expectations, Tak believes that these potential therapies’ administration directly into tumors will prove a key edge.

There’s no timeline yet on when the research from this partnership will reach the clinic, with Tak saying it’s still too early to forecast. Candel and Penn could move quickly if they wanted to, he added, but he’s not making any promises just yet. Either way, he notes that there is a sense of urgency around getting these drugs to patients.

“Based on the flexibility of the technology, and based on the severity of the disease we go after, the belief is that this would be a relatively quick development path if things go well from a scientific perspective,” Tak said. “I don’t think anyone could move faster in this space based on the combined capabilities, but that can’t be conveyed in any timeline to the external environment.”

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