New Vaccines Eradicate Large Tumours and Tumour Metastases

As cancer cells continuously mutate their DNA, they also produce proteins that are altered from their normal counterparts by small changes in their peptide sequences. Just like every cell in our body presents part of its peptide repertoire to our immune system to identify itself as “self,” cancer cells present their faulty neopeptides (or neoantigens), revealing themselves as foreign or “non-self.” After taking up these neoantigens, the immune system’s dendritic cells (DCs) can initiate strong T cell responses to attack the very cancer cells that express them.

Cancer researchers have recognized the potential of neoantigens as vaccine targets, and in animal models and early human clinical trials, they succeeded in identifying and creating cocktails of neoantigens to vaccinate patients against their own cancers. Generating effective vaccines, however, is still a challenging and cumbersome 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 DCs.

A new 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 immune therapy 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 Wyss Institute Core Faculty member David Mooney, Ph.D., who led the study. He is also leader of the Wyss Institute’s Immunomaterials Platform and the Robert P. Pinkas Family Professor of Bioengineering at SEAS.

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