Innovation Management

High-precision radiosurgery of tumors

Teaming up with Accuray, a leading player in radiooncology and radiotherapy, DKFZ researchers have developed a beam-shaping device with continual image guidance in three dimensions known as an Iris Variable Aperture Collimator. The device permits precision radiosurgery of tumors, with treatment tailored to individual needs using the CyberKnife® system from Accuray. Accuray has concluded a license and cooperation agreement with the DKFZ in order to expand cooperation in the field of radiooncology.

Links:

http://www.dkfz.de/de/medphys/

http://www.presseportal.de/pm/61356/2257975

Breaking the diffraction barrier

In 2014 Stefan Hell received the Nobel Prize in Chemistry for the development of nanoscopy – high-resolution light microscopy beyond the diffraction limit of light as defined by Abbe's Law. Patent-protected inventions by Hell and his team from the Laboratory for Optical Nanoscopy at the DKFZ were licensed out to Abberior Instruments, which is a spin-off of the Max Planck Society. They are used to manufacture microscopes that achieve hitherto unprecedented spatio-temporal resolution for the observation of dynamic processes in cells.

Links:

http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2014/hell-lecture.html

http://www.abberior-instruments.com/home/

https://www.dkfz.de/de/presse/pressemitteilungen/2015/dkfz-pm-15-36-Das-schnellste-Nanoskop-der-Welt.php

Innate Cell Engagers improve the anti-tumor activity of immune cells

Affimed is a DKFZ spin-off company that specialises in the development of bispecific antibodies, known as Innate Cell Engager (ICE®), which lead innate immune cells to target and destroy cancer cells. Results from clinical trials indicate that Affimed’s ICE® molecules AFM13 and AFM24 exhibit well manageable safety profiles in CD30-positive lymphomas and EGFR-expressing solid tumors, respectively and show promising signs of therapeutic activity. Besides the development of monotherapies, combinations with NK cells or other immune-oncologic agents have shown promising results, partly with unprecedented efficacy rates.

Links:
https://www.affimed.com 

Software for improved diagnosis and therapy planning

Mint Medical GmbH, a spin-off from the DKFZ in 2010, has worked on developing radiology imaging in order to improve both the diagnosis and therapeutic strategies and procedures in cancer. Its methods for the automated analysis of image data increase the quality, diagnostic reliability, and efficiency of the entire radiological process from diagnosis to therapy planning, therapy, and therapy follow-up.

Links:

https://mint-medical.com/de/

http://www.dkfz.de/de/presse/pressemitteilungen/2010/dkfz_pm_10_36_DKFZ-Firmenausgruendung-Mint-Medical-erhaelt-Hightech-Preis.php

Early detection of cervical cancer

mtm laboratories AG, a Heidelberg company, spun off from the DKFZ in 1999. It developed in vitro diagnostics (IVD) for the early detection and diagnosis of cervical cancer that provide outstanding sensitivity and specificity compared with conventional tests. The technology is based on the immunocytochemical detection of the overexpression of the human p16 protein in cells undergoing HPV-mediated transformation, which may lead to cervical cancer. Having developed, produced, clinically validated, and marketed IVD tests for cervical histology and cytology worldwide on the basis of the p16 biomarker, mtm laboratories was sold to Roche for up to 190 million EUR (130 million upfront plus 60 million EUR milestone) in 2011.

Links:

https://www.gesundheitsindustrie-bw.de/fachbeitrag/aktuell/diagnostik-zur-frueherkennung-des-gebaermutterhalskrebses 

Cell type diagnosis of metastases using antibodies to cytoskeletal proteins

Cell type-specific antibodies to intermediate filaments and to the desmosomal proteins of cell-cell adherens junctions developed at the DKFZ are now used worldwide; they are among the most frequently published antibodies in the entire biomedical and cell biological literature. It was cell biologist Werner Franke and his co-workers at the DKFZ that demonstrated that cell type-specific variants of components of the cytoskeleton retain their specificity in cancer cells too. They showed that by employing antibodies to these variants, it is possible to make a cell type diagnosis of cancer metastases, even if the original tumor is unknown. In order to make these antibodies for cancer diagnostics available for scientists worldwide, Franke and colleagues in Heidelberg founded PROGEN Biotechnik GmbH in 1983, one of Germany's first biotech companies.

Links:

http://www.dkfz.de/de/helmholtz-zellbiologie/Franke-in-Cancer_Research_DKFZ_2014_web.pdf

A radionuclide-coupled substance for the diagnosis and treatment of prostate cancer

Scientists at DKFZ developed PSMA-617, a compound that binds specifically to the prostate-specific membrane antigen (PSMA), which is highly overexpressed in prostate cancer cells. When the diagnostic agent PSMA-11 is labeled with the weakly radioactive radionuclide Gallium-68 (68Ga), it can be used in positron emission tomography (PET) to visualize even tiny clusters of prostate cancer cells. Conversely, when PSMA-617 is labeled with the strongly radioactive radionuclide Lutetium-177 (177Lu), it can specifically target and destroy cancer cells.

This innovative technology was initially licensed to the German biotech firm ABX advanced biochemical compounds GmbH and later to Endocyte Inc. in the USA. Novartis acquired Endocyte in October 2018. In 2022, Novartis received approval for PSMA-617 in both the USA and Europe and markets this novel therapeutic as Pluvicto.

Antibody microarrays for screening of biomarkers in cancer

The biotech company Sciomics GmbH, a spin-off from the DKFZ in 2013, produces protein-based affinity microarrays for proteome analyses in research and clinical medicine. With the complex, high-density microarrays from cancer-relevant antibodies developed at the DKFZ, various biomarker signatures have been developed, filed for patenting, and published. The microarrays may be important for the diagnosis, prognosis, and prediction of cancer.

Links:

www.sciomics.de

http://www.dkfz.de/de/presse/pressemitteilungen/2014/dkfz-pm-14-31-Protein-Test-statt-Blasenspiegelung.php

Competency cluster in imaging and radiotherapy: the alliance with Siemens Healthcare

Radiologists, radiooncologists and medical physicists from the DKFZ are cooperating with Siemens Healthineers, one of Germany’s leading medical technology companies. Within this collaboration, Siemens provides the latest technological advancement, development know-how, and technological infrastructure, while the scientists of DKFZ contribute their expertise in radiotherapy, medical physics and radiological imaging to develop new procedures in cancer diagnostics and treatment. The foundations for this cooperation, such as the 7 Tesla high field MRI scanner, housed in a dedicated building on the Neuenheimer Feld campus, are aiding the doctors of radiology, neuroradiology and radiation oncology at Heidelberg University Hospital and the Heidelberg Ion Beam Therapy Center.

Links:
https://www.siemens-healthineers.com/press/releases/pr-20190911034shs.html 
https://www.siemens-healthineers.com/de/news/ionenstrahltherapie.html 
https://www.dkfz.de/en/presse/pressemitteilungen/2017/dkfz-pm-17-35c-Double-imaging-of-prostate-cancer.php 

Detecting and combating cancers through cancer stem cell research

HI-STEM gGmbH is a non-profit public-private partnership between the German Cancer Research Center (DKFZ) in Heidelberg and the Dietmar Hopp Foundation. HI-STEM performs cutting-edge research to investigate the molecular principles of normal and malignant stem cells in healthy tissues, cancer and metastasis. HI-STEM develops novel diagnostic and treatment strategies to improve early cancer detection, precision oncology to target leukemic and solid tumor stem cells as well as regenerative therapies.

Cancer cells with stemness properties (leukemic or solid cancer stem cells) are responsible for therapy resistance and consequently drive relapse and metastases, which are the main cause of cancer related deaths. Cancer stem cells (CSCs) can stay dormant in their stem cell niche for long periods of time within the tumor which mediates their insensitivity to anti-proliferative treatment schemes such as chemotherapy. Upon re-activation however, these cells can cause rapid relapse even after a seemingly positive response to therapy.

Links:

https://www.hi-stem.de

ProtaGene Continues the Legacy of GeneWerk's Commitment to Safer Gene and Cell Therapies

GeneWerk was founded in 2014 as a spin-off of the German Cancer Research Center (DKFZ) and the National Center for Tumor Diseases (NCT) by Christof von Kalle and his colleagues, Manfred Schmidt and Annette Deichmann. The company's mission was to provide molecular-genetic and bioinformatic analyses supporting the development of safer and higher-quality gene and cell therapies throughout pre-clinical and clinical research processes.

GeneWerk acquired equity investment from Ampersand Capital Partners in 2020 to expedite its growth and establish a U.S. market presence. Then, in July 2021 GeneWerk, BioAnalytix, and Protagen Protein Services (PPS) merged to form ProtaGene.

The beLAB2122 initiative is a multi-year partnership between DKFZ, the Universities of Heidelberg, Tübingen, and Frankfurt, EMBL, Evotec, and Bristol Myers Squibb (BMS). It aims to identify and develop novel therapeutic targets and technology platforms with the goal of launching new spin-out companies.

beLAB2122 provides funding, technology platforms, and mentoring to achieve preclinical proof of concept. Selected projects receive further support in building business cases, securing investment, and progressing towards commercialization.

Since 2008, DKFZ and Bayer AG have collaborated to translate preclinical research into new therapies The alliance has initiated 67 projects selected from more than 160 proposals, leading to multiple drug development milestones. Four compounds have entered Phase 1 clinical trials, and Bayer AG licensed results from 10 projects with one still active as of today.

In 2013, the collaboration expanded with the creation of a joint immuno-oncology laboratory where DKFZ and Bayer researchers work side by side. This lab has contributed to three out of four Investigational New Drugs (INDs) developed under the alliance. In addition, the alliance has resulted in over 20 high-impact publications and 22 active patent families. The expertise gained in preclinical development will continue to benefit other collaborations and DKFZ’s spin-offs.

Example: BAY 2965501, developed by Bayer AG and DKFZ, is a selective, oral DGK-ζ (zeta) inhibitor that enhances T-cell activation by overcoming immune suppression. Preclinical studies show strong efficacy in tumor models with a favorable safety profile. A first-in-human phase I trial (NCT05614102) is enrolling patients with advanced solid tumors to evaluate safety, pharmacokinetics, and anti-tumor effects. BAY2965501 Clinical Trial

References:

Zuccotti, A., Carretero, R., & Hess-Stumpp, H. (2024). The alliance between the German Cancer Research Center and Bayer: A retrospective of an innovative collaboration model. In M. C. Michel & H. A. Wieland (Eds.), Public-private partnerships in drug research and development (pp. 83-95). Publisher. 

Wellenreuther R., Keppler, D., Mumberg, D. Ziegelbauer, K. Lessl, M. (2012) Promoting drug discovery by collaborative innovation: a novel risk- and reward-sharing partnership between the German Cancer Research Center and Bayer HealthCare. Drug Discov Today. 2012 Nov;17(21-22):1242-8. https://doi.org/10.1016/j.drudis.2012.04.004

In 2023, DKFZ joined the Sanofi Innovation Awards Europe (Sanofi iAwards) program, which supports collaboration between academic institutions and industry. DKFZ researchers can apply for funding of up to €120,000 per project for early-stage, disease-relevant research. The program facilitates knowledge exchange with Sanofi’s R&D teams and aims to develop promising projects into sponsored research programs, licensing agreements, or start-ups. Two DKFZ proposals were selected in 2023 and 2024 through a peer review process.