Novartis will partner with researchers from the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Dana-Farber Cancer Institute to develop biomaterial systems for second-generation cancer immunotherapies, the pharma giant and the Institute said today, through a collaboration whose value was not disclosed.

Researchers from the Wyss Institute and Dana-Farber have worked with colleagues at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) to engineer the biomaterial systems for new cancer vaccines.

The technology consists of implantable immuno-material designed to activate endogenous immune cells inside the body to launch an attack on the patient's own cancer. The novel technique was developed, incubated, and advanced at SEAS and the Wyss Institute by David Mooney, Ph.D., Robert P. Pinkas Family Professor of Bioengineering at SEAS, and core faculty member and lead of the Immuno-Materials initiative at the Wyss Institute.

“This work resulted from a remarkable cross-disciplinary effort using the combined expertise of bioengineers, cancer biologists, and immunologists,” Dr. Mooney said in a statement. “We have demonstrated that these biomaterials can be easily delivered to patients, provide sustained and local release of immune-modulating factors, and bypass the need for modification of cells outside the body. This concept has led to a very promising platform for cancer immunotherapy.”

According to Novartis, the biomaterial systems are designed to provide sustained delivery of immunotherapies and target specific types of cancer—thus overcoming hurdles that have hampered traditional cancer vaccines, including their limited duration of action and lack of targeting to specific cancer cells.

The systems to be developed consist of porous scaffold material made from a biodegradable medical polymer infused with inactivated antigens from the patient’s tumor cells, as well as immunostimulatory molecules designed to attract dendritic cells of the immune system to the immuno-material site, then activate them to stimulate a host response. After activation, the dendritic cells home to nearby lymph nodes to orchestrate antitumor responses throughout the body.

The systems have been shown to release cell-recruiting factors that attract host dendritic cells and present tumor antigens to those specialized immune cells, with the aim of bolstering immune responses to cancer. The approach differs from cell-based cancer immunotherapies, which depend on manipulating immune cells outside of the body, then transferring them into patients, the Wyss Institute said.



This animation explains how the Wyss Institute’s cancer vaccine technology was developed in a collaboration between biologists, clinicians, and researchers at the Institute, the Dana-Farber Cancer Institute, and the Harvard John A. Paulson School of Engineering and Applied Sciences. It works by reprogramming the immune system to reject cancer cells. [Wyss Institute at Harvard University]

Tumor-Shrinking Potential

In preclinical studies, a research team headed by Dr. Mooney and Glenn Dranoff, M.D.—who at the time was a Wyss Institute associate faculty member and co-leader of Dana Farber’s Cancer Vaccine Center—showed that the cancer vaccine could potentially shrink or eradicate multiple types of tumors, in addition to providing prophylactic protection, in various animal models. Dr. Dranoff is now global head of exploratory immuno-oncology at the Novartis Institutes for Biomedical Research.

Following the preclinical studies, the Wyss Institute and Dana-Farber in 2013 launched a Phase I clinical trial at Dana-Farber designed to test the safety of the first of the implantable, immuno-material-based cancer vaccines in patients with melanoma. F. Stephen Hodi, Jr., M.D., director of DFCI’s Melanoma Center and a professor at Harvard Medical School, leads the trial, which is still ongoing. Development and study of the cancer vaccine was funded by the Wyss Institute, Dana-Farber, and the NIH.

According to Novartis, the biomaterial-based systems hold promise because of their potential to serve as engineered microenvironments to educate the immune system about cancer and initiate immune responses against tumors over a sustained period of time.

Novartis will have worldwide rights, in target-limited applications, to further develop and translate the technology into new vaccines under its licensing agreement with Harvard's Office of Technology Development. Technologies licensed under the agreement for target-specific applications are owned or co-owned by Harvard, as well as Dana-Farber and the University of Michigan.

“Our collaborators have combined the fields of immuno-oncology and material science to develop novel platforms for delivering immunotherapies to combat cancer,” Jay Bradner, M.D., president of the Novartis Institutes for BioMedical Research (NIBR), said in a company statement. “We look forward to collaborating with the Wyss Institute to further develop this technology in conjunction with our growing immunotherapy portfolio.”

Researchers from Novartis and the Wyss Institute will partner to further develop the biomaterial systems in order to support combination regimes for second-generation immunotherapy regimens.

Novartis won the FDA’s first approval in August for a chimeric antigen receptor T-cell (CAR-T) cancer immunotherapy, Kymriah™ (tisagenlecleucel). But in recent years, the company has stressed efforts to develop a series of second-generation immuno-oncology treatments. In its 2017 Annual Report, released January 24, Novartis said it has 18 immuno-oncology candidates in development. The most advanced of these is PDR001 (spartalizumab), an anti-programmed cell death 1 (PD-1) antibody designed to help the immune system recognize and attack tumors.

Novartis inherited PDR001 when it acquired CoStim Pharmaceuticals in 2014 for an undisclosed price. PDR001 is under study in 25 clinical trials, as a single agent or in combinations, Novartis said—including two Phase III trials for which data is set to be released in 2019, according to the company’s website. One is assessing PDR001 in malignant melanoma with Novartis’ marketed combination treatment of Tafinlar® (dabrafenib) and Mekinist® (trametinib). The other is assessing PDR001 in endocrine neoplasm.

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