Cancer Vaccines May Become Personal

Harvard and Dana-Farber Cancer Institute describe a vaccine approach to battle patients' own cancer

Innovative cancer vaccine researchers have recognized the potential of neoantigens as realistic vaccine targets.

Researchers from Harvard and Dana-Faber report they succeeded in identifying and creating cocktails of neoantigens to vaccinate patients against their own cancers.

Generating effective vaccines, however, is still a challenging endeavor, as neoantigen-containing vaccine components often require complex chemical or physical modifications.

And, the neoantigens can be cleared from the body rapidly, which potentially limits their presentation to immune system’s dendritic cells (DC).

A limited mice study published by a team of researchers at Harvard’s Wyss Institute for Biologically Inspired Engineering, the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Dana-Farber Cancer Institute describes a vaccine approach that uses an injectable scaffold loaded with a selection of tumor-expressed peptides.

In mouse models, the vaccines were shown to eradicate large tumors and tumor metastases, create a memory of tumors enabling future tumor rejections and strongly synergize with checkpoint therapy, a different immunotherapy approach that is used clinically to restimulate fading anti-tumor immunity in cancer patients.

“There is tremendous enthusiasm for using neoantigens in immunotherapy as predicting them in individual tumors becomes more and more reliable. Our materials approach is able to mix and match predicted neoantigens very easily and efficiently in a single scaffold that as a delivery vehicle could be plugged into existing pipelines to enable more effective personalized cancer treatments,” said David Mooney, Ph.D., who led this study.

The team leveraged their previously developed programmable biomaterial made from tiny mesoporous silica rods (MSRs) that can be injected under the skin where they spontaneously assemble into a 3-dimensional scaffold that is able to attract and stimulate DCs.

In their new study, they coated the MSRs with polyethyleneimine (PEI), a polymer that has been previously used to deliver DNA and proteins to cells and that was surmised to have immune-stimulatory effects.

“This allowed us to achieve two things,” said first-author Aileen Li, Ph.D., who is a Postdoctoral Fellow at the University of California San Francisco.

  • it enabled ready absorption of multiple peptides regardless of their inherent properties without the need to further modify them; and
  • by being taken up by DCs together with the peptides, PEI enhanced the stimulation of DCs and the ensuing tumor-directed cytotoxic T cell responses in our mouse models.

In addition to the PEI coating, the vaccines also contained factors that help them attract DCs and boost immune functions.

Comparing them to control vaccines that lacked PEI but that had all other components, the team found them to be considerably more efficient in activating DC populations, stimulating their interactions with T cells in nearby lymph nodes, and driving the generation of circulating killer T cells that are capable of recognizing the tumor-specific peptides.

Raising this strategy’s clinical potential, these advances also translated to mouse models with clinically more relevant tumors that the researchers investigated.

“This new biomaterials-based cancer vaccine therapy has enormous clinical potential as it markedly enhances our ability to attack tumors by harnessing the very process that lets them arise in the first place. It is an exciting next step in the immuno-oncology field,” said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D.

Additional authors on the study are Soumya Badrinath, Ph.D., and Kai Wucherpfennig, M.D., Ph.D., from the Dana-Farber Cancer Institute; Ph.D. Students Miguel Sobral and Maxence Dellacherie, and Graduate Student Ting-Yu Shih on Mooney’s team at the Wyss Institute and SEAS; Wyss Institute Senior Research Scientist James Weaver, Ph.D., Wyss Staff Scientist Alexander Stafford and Staff Veterinarian Amanda Graveline, D.V.M.; Omar Ali, Ph.D., a former Wyss Institute Staff Scientist; and Jaeyun Kim, Ph.D., a former Postdoctoral Fellow on Mooney’s team who now is Associate Professor at Seoul National University.

The study was funded by Harvard’s Wyss Institute for Biologically Inspired Engineering, the National Institutes of Health, the Melanoma Research Alliance Foundation, and the National Science Foundation.