The Institute of Translational Oncology (TRON) together with BioNTech AG today announced the publication of a joint paper in the international journal Cancer Research that describes a new path for individually tailored cancer therapy. An interdisciplinary team of genome scientists and immunologists led by the cancer researcher Prof. Ugur Sahin for the first time demonstrated that whole cancer genome information could be used to tailor effective cancer specific vaccines.
The researchers applied Next Generation Sequencing (NGS) for discovery of somatic point mutations in a mouse melanoma. The identified mutations were then used as a template to synthesize multiple peptide antigens for vaccination studies. The group identified a surprisingly frequent immunogenicity of such mutations allowing them to be used as vaccine targets. Moreover, the authors demonstrated that even single well-chosen mutated targets are sufficient to induce therapeutic immune responses able to inhibit the growth of mouse melanoma tumors. The finding is of high relevance as human cancers carry up to hundreds of somatic mutations, thereby providing a rich source for design of novel cancer vaccines.
“Up to now, there had been no comprehensive experimental data on the immunogenicity of somatic mutations from tumors,” says Dr. John Castle, co-author and head of the NGS-team at TRON. “Using NGS technology and peptide vaccination, we were able to design the first mouse tumor exome-capture study and showed that mutations can be a source for individualized vaccination therapies.” Co-author Dr. Sebastian Kreiter adds: “Our data show that around 30 % of the sequences we used for vaccination were immunogenic and led to lymphocyte expansion.”
“The findings encourage us to proceed towards clinical translation of our concept,” explains Prof. Ugur Sahin, principal investigator and head of the TRON and BioNTech research teams. “Targeting multiple mutations may be the key to address a central problem in cancer therapy- the cellular and genomic heterogeneity of tumors allowing cancer cells to escape conventional treatments. In our concept, the multiplicity of mutations is the Achilles heel of cancer, making tumors vulnerable to genome tailored actively personalized cancer vaccines”.
TRON – Translational Oncology at University Medical Center Mainz and BioNTech AG