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Candel Therapeutics, UPenn Collaborate on Viral/CAR-T Combo Therapy Development – Inside Precision Medicine

Candel Therapeutics, a clinical stage developer of viral immunotherapies, announced Wednesday that it will collaborate with researchers at the University of Pennsylvania’s (UPenn) Center for Cellular Immunotherapies to study the efficacy of using viral immunotherapies to help boost the effects of UPenn’s CAR-T cell therapies in solid tumor models.
The research will evaluate Candel’s enLIGHTEN Discovery Platform which will provide herpes simplex virus (HSV) vectors containing selected transgenes in combination with investigational CAR-T cell therapies at UPenn. Under the terms of the agreement, each party will retain full ownership of their respective intellectual property and will retain right to proceed to clinical trials to further study the impact of any promising combinations developed.
“This discovery partnership with Penn as a first step towards evaluating the impact of innovative viral immunotherapies in combination with CAR-T cells with the aim of modulating the tumor microenvironment in such a way that CAR-T cells can get into the solid tumor, stay functional, and eliminate tumor cells,” said Paul Peter Tak, president and CEO of Candel Therapeutics. “Our HSV constructs, based on the enLIGHTEN Discovery Platform, permit precise tuning of important viral properties and, with a large payload capacity, enable multimodal approaches to fight cancer.”
UPenn’s team for the research will be headed by Neil Sheppard, an adjunct associate professor of Pathology and Laboratory Medicine in the Perelman School of Medicine who serves as Director of the T Cell Engineering Lab. The lab operates within the Center for Cellular Immunotherapies led by Carl June, a pioneer in the field of immunotherapy, whose drug tisagenlecleucel (Kymriah) was the first approved gene therapy.
Despite many breakthroughs in the development of CAR-T therapies for the treatment of hematological tumors, there remain a number of challenges in applying them to solid tumors due to the fact that CAR-T cells return to the blood stream and may have difficulty penetrating the solid tumor.
“The solid tumor microenvironment presents numerous challenges to effective cell therapy including stromal barriers, impaired T-cell trafficking and function, poor T-cell expansion and persistence, and an overall suppressive biological milieu,” Sheppard said. “We are excited to work with Candel to address each of the challenges posed by the solid tumor microenvironment simultaneously, which represents a new approach to immunotherapy.”
For Candela, the collaboration with UPenn fits directly with company’s immunotherapy philosophy of delivering a therapy to the tumor site that have both a cytotoxic component while also stimulating and enhancing immune response to the tumor. The company’s lead program is CAN-2409 an adenovirus-based replication deficient engineered gene construct encoding the thymidine kinase gene derived from HSV. It is currently in Phase III clinical trials in prostate cancer and is also being evaluated in brain cancer as a single agent and in combination with nivolumab (Opdivo), in non-small cell lung cancer as a combination therapy with PD-1/PD-L1 immune checkpoint inhibitors, and in advanced non-metastatic pancreatic adenocarcinoma.
For its HSV platform, which is being leveraged in the UPenn collaboration, the company also has an early clinical trial for CAN-3110, a novel herpes simplex viral vector, for the treatment of glioma.

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