DNA origami vaccines for precise cancer immunotherapy: Study

A team of scientists from the Wyss Institute at Harvard University, Dana-Farber Cancer Institute (DFCI), Harvard Medical School (HMS), and Korea Institute of Science and Technology (KIST) created a DNA origami platform called DoriVac, whose core component is a self-assembling square block-shaped nanostructure.

The findings were published in the Journal Nature Nanotechnology.

Therapeutic cancer vaccines, a promising form of immunotherapy, target and eliminate cancer cells while preventing recurrence and spread. They contain tumor antigens, including neoantigens, stimulating the immune system. Adjuvant molecules activate antigen-presenting cells (APCs), which present antigens to T cells, triggering rapid tumor response and long-term immunity.

The DNA origami vaccine enables precise attachment of adjuvant molecules and tumor antigens on a square block. Spacing CpG adjuvant molecules 3.5 nanometers apart effectively stimulated APCs, generating cytotoxic T cells, Th-1 polarized T cells, and memory T cells. DoriVac vaccines also improved tumor control and mouse survival, particularly when paired with immune checkpoint inhibitors.

“DoriVac’s DNA origami vaccine technology merges different nanotechnological capabilities that we have developed over the years with an ever-deepening knowledge about cancer-suppressing immune processes. We envision that in the future, antigens identified in patients with different types of tumors could be quickly loaded onto prefabricated, adjuvant-containing DNA origami to enable highly effective personalized cancer vaccines that can be paired with FDA-approved checkpoint inhibitors in combination therapies,”said Wyss Faculty member William Shih, Ph.D., who led the Wyss Institute team together with first-author Yang (Claire) Zeng, M.D., Ph.D.

Zeng and colleagues created DoriVac vaccines with varying distances between CpG strands and attached antigens on a square block. They used a method to protect the structures from degradation in the body. The DoriVac vaccines enhanced antigen uptake by APCs, especially dendritic cells. A spacing of 3.5 nanometers between CpG strands yielded the most potent APC responses, surpassing control vaccines with free CpG molecules.

“The DoriVac platform is our first example of how our pursuit of what we call Molecular Robotics can lead to entirely new and powerful therapeutics. This technology opens an entirely new path for development of designer vaccines with properties tailored to meet specific clinical challenges. We hope to see its rapid translation into the clinic,” said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and Boston Children’s Hospital.

Reference:Yang C. Zeng, Olivia J. Young, Christopher M. Wintersinger, Frances M. Anastassacos, James I. MacDonald, Giorgia Isinelli, Maxence O. Dellacherie, Miguel Sobral, Haiqing Bai, Amanda R. Graveline, Andyna Vernet, Melinda Sanchez, Kathleen Mulligan, Youngjin Choi, Thomas C. Ferrante, Derin B. Keskin, Geoffrey G. Fell, Donna Neuberg, Catherine J. Wu, David J. Mooney, Ick Chan Kwon, Ju Hee Ryu & William M. Shih; Fine tuning of CpG spatial distribution with DNA origami for improved cancer vaccination; Journal: Nature Nanotechnology