First preclinical proof-of-concept of mutation-based individualized cancer vaccine / Deep sequencing of immunogenic mutations may pave way for customized immunotherapy

Mainz (ots) - 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".

References: John C. Castle, Sebastian Kreiter, Jan Diekmann, Martin
Löwer, Niels von de Roemer, Jos de Graf, Abderraouf Selmi, Mustafa
Diken, Sebastian Boegel, Claudia Paret, Michael Koslowski, Andreas N.
Kuhn, Cedrik M. Britten, Christoph Huber, Özlem Türeci, Ugur Sahin.
Exploiting the mutanome for tumor vaccination. Cancer Research.
Published online January 11, 2012.

About TRON

TRON - Translational Oncology at the University Medical Center of the
Johannes Gutenberg University Mainz, is a biopharmaceutical research
organization that pursues new diagnostics and drugs for the treatment
of cancer and other diseases of the immune system. TRON aims to
develop novel platforms for individualized therapies and biomarkers,
translating basic research into drug applications. TRON partners with
academic institutions, biotech companies and the pharmaceutical
industry, executing research with leading-edge technologies and
supporting the development of innovative drugs with its unique
expertise and infrastructure. For more information visit
www.tron-mainz.de

About BioNTech

BioNTech (Biopharmaceutical New Technologies) AG is a holding of
leading biotechnology companies focussing on the development of
innovative diagnostic and therapeutic approaches for cancer and
life-threatening diseases. BioNTech integrates a broad portfolio of
disease specific molecular biomarkers and cutting edge drug
development platforms that enable the development of fully
personalized cancer immunotherapy approaches.

Rückfragehinweis:
Christine S. Castle
Communications Director
TRON
Tel: +49 (0) 6131 178166
Mail: [email protected]

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