A new biologically inspired “injectable cryogel whole-cell cancer vaccine” combines patient-specific harvested cancer cells and immune-stimulating chemicals or biological molecules to help the body attack cancer. It has been developed by scientists at Harvard’s Wyss Institute and Dana-Farber Cancer Institute.

This new approach is simpler and more economical than other cancer cell transplantation therapies, which harvest tumor cells and then genetically engineer them to trigger immune responses once they are transplanted back into the patient’s body, the researchers say.

The research, headed by Wyss Core Faculty member David Mooney, Ph.D., was reported online in an open-access paper in Nature Communications on August 12.

Minimally invasive cryogels



The new anti-cancer vaccine uses the patient’s own cancer cells to trigger immune responses. The cryogels are a type of hydrogel made up of hydrophilic (water-compatible) polymer chains that are cross-linked and can hold up to 99 percent water.

They are created by freezing a solution of the polymer that is in the process of gelling. When thawed back again to room temperature, the substance turns into a highly interconnected pore-containing hydrogel, which is similar in composition to bodily soft tissues in terms of their water content, structure, and mechanics.

By adjusting their shape, physical properties, and chemical composition, Mooney’s team generated sponge-like, porous cryogels that can be infused with living cells, biological molecules, or drugs for a variety of potential therapeutic applications, including cancer immunotherapy.

The cryogels are minimally invasive because of their extreme flexibility and resilience, enabling them to be compressed to a fraction of their size and injected underneath the skin via a surgical needle. Once injected, they quickly bounce back to their original dimensions to do their job.

“After injection into the body, the cryogels can release their immune-enhancing factors in a highly controlled fashion to recruit specialized immune cells, which then make contact and read unique signatures off the patient’s tumor cells, also contained in the cryogels,” said Sidi Bencherif, the study’s co-first author and a Research Associate in Mooney’s research group.

This has two consequences, he said: “Immune cells become primed to mount a robust and destructive response against patient-specific tumor tissue and the immune tolerance developing within the tumor microenvironment is broken.”

Shrinking tumors

In experimental animal models on melanoma (skin) tumors, results show that using the cryogel to deliver whole cells and drugs triggers a dramatic immune response that can shrink tumors and even prophylactically (in advance) protect animals from tumor growth. With the pre-clinical success of the new cancer cell vaccination technology, Mooney and his team are going to explore how this cryogel-based method could be more broadly useful to treat a number of different cancer types.

“This new injectable form of this biomaterials-based cancer vaccine will help to expand the cancer immunotherapy arsenal, and it’s a great example of how engineering and materials science can be used to mimic the body’s own natural responses in a truly powerful way,” said Don Ingber, the Wyss Institute’s Founding Director, who also is the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and Professor of Bioengineering at SEAS.

Mooney is also the Robert P. Pinkas Family Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.

Abstract of Injectable cryogel-based whole-cell cancer vaccines

A biomaterial-based vaccination system that uses minimal extracorporeal manipulation could provide in situ enhancement of dendritic cell (DC) numbers, a physical space where DCs interface with transplanted tumour cells, and an immunogenic context. Here we encapsulate GM-CSF, serving as a DC enhancement factor, and CpG ODN, serving as a DC activating factor, into sponge-like macroporous cryogels. These cryogels are injected subcutaneously into mice to localize transplanted tumour cells and deliver immunomodulatory factors in a controlled spatio-temporal manner. These vaccines elicit local infiltrates composed of conventional and plasmacytoid DCs, with the subsequent induction of potent, durable and specific anti-tumour T-cell responses in a melanoma model. These cryogels can be delivered in a minimally invasive manner, bypass the need for genetic modification of transplanted cancer cells and provide sustained release of immunomodulators. Altogether, these findings indicate the potential for cryogels to serve as a platform for cancer cell vaccinations.