Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Novel combination of antibodies leads to significant improvement in cancer immunotherapy

02.01.2020

The simultaneous use of antibodies based on two differing mechanisms of action leads to a more effective destruction of tumors. This has been demonstrated by a study in animal models by medical oncologists and scientists at the University of Basel that has been published in the scientific journal PNAS. Patients who do not respond to current immunotherapy options could benefit most from this new treatment.

In recent years, immunotherapies against cancer have raised great hopes. These novel therapies recruit the body’s immune system to destroy cancerous tissue.


An antibody that activates the CD40 receptor on the surface of immune cells and thus stimulates the production of natural killer T-cells showed a promising effect in preclinical studies.

However, in subsequent clinical trials, the success of the CD40 antibody fell far short of expectations – less than 20% of patients responded. The research group Cancer Immunology at the University of Basel has now shown in animal models that the effect of the anti-CD40 antibody can be increased significantly by combining it with two other antibodies that attach to tumor blood vessels.

Open the way to the tumor

The starting point for the study was the observation that the administration of anti-CD40 antibodies leads to an increase in killer T-cells as intended – but these can then only be detected in the peripheral areas and not in the interior of the tumor. The researchers suspected that this was due to the nature of the tumor’s blood vessels.

“Normally, the blood vessels of a tumor are leaky or stunted. Therefore, there is no good way for killer T-cells to get inside,” says study leader Dr. Abhishek Kashyap. “Our hypothesis was that the killer cells are able to invade the tumor and destroy it only if there are enough healthy blood vessels.”

Therefore, they combined the anti-CD40 antibody with two other anti-angiogenic antibodies that are able to stabilize the tumor blood vessels. One of the anti-angiogenetic antibodies is already approved for cancer therapy under the name Avastin, while the other is still in clinical development. All antibodies were provided by Roche.

New combination destroys tumor tissue

The researchers then tested this new combination of antibodies in several animal models for different types of cancer, such as colorectal, breast and skin cancer. As expected, the combination of the three antibodies significantly improved tumor tissue destruction in all cancers.

A more detailed analysis also showed that this success was based on the predicted mechanism: the addition of the two anti-angiogenetic antibodies ensured the tumors had more intact blood vessels.

Unexpectedly, however, the investigations also showed that the antibody combination very effectively strengthens the immune system in several ways; for example, through a better penetration of the tumor by killer cells and by promoting a tumor-hostile inflammatory reaction in the tumor microenvironment.

“Our results illustrate how important it is to understand the biology of tumors,” says Kashyap. He believes that patients with ‘cold’ tumors – tumors that do not respond well to immunotherapy – could benefit most from this new combination. “The anti-angiogenetic antibodies may make the ‘cold’ tumors ‘hot’, so that immunotherapy functions better.” In the meantime, several early clinical trials of similar therapies in humans are underway.

Cooperation strengthens results

According to Kashyap, the strength of the study lies not only in the large effects measured, but also in the fact that several different laboratories achieved the same results. The experiments were carried out at the University Hospital of Basel, EPFL and the Roche Innovation Center Zurich.

This is also confirmed by Alfred Zippelius, Professor of Translational Oncology at the University of Basel and senior author of the study: “The innovative and translational potential of this work is the result of a close and excellent collaboration between applied and basic research, between the University of Basel and EPFL, and between academia and industry.”

Wissenschaftliche Ansprechpartner:

Prof. Dr. Alfred Zippelius, University of Basel / University Hospital Basel, Departement of Biomedicine, Tel. +41 61 328 60 16, E-Mail: alfred.zippelius@usb.ch

Originalpublikation:

Abhishek S. Kashyap, Martina Schmittnaegel, Nicolò Rigamonti, Daniela Pais-Ferreira, Philipp Mueller, Melanie Buchi, Chia-Huey Ooi, Matthias Kreuzaler, Petra Hirschmann, Alan Guichard, Natascha Rieder, Ruben Bill, Frank Herting, Yvonne Kienast, Stefan Dirnhofer, Christian Klein, Sabine Hoves, Carola H. Ries, Emily Corse, Michele De Palma, Alfred Zippelius
Optimized anti-angiogenic reprogramming of the tumor microenvironment potentiates CD immunotherapy
PNAS (2019), doi: 10.1073/pnas.1902145116

https://www.pnas.org/cgi/doi/10.1073/pnas.1902145116

Reto Caluori | Universität Basel
Further information:
http://www.unibas.ch

More articles from Life Sciences:

nachricht New self-assembled monolayer is resistant to air
22.01.2020 | University of Groningen

nachricht Mosquitoes are drawn to flowers as much as people -- and now scientists know why
22.01.2020 | University of Washington

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New roles found for Huntington's disease protein

Crucial role in synapse formation could be new avenue toward treatment

A Duke University research team has identified a new function of a gene called huntingtin, a mutation of which underlies the progressive neurodegenerative...

Im Focus: A new look at 'strange metals'

For years, a new synthesis method has been developed at TU Wien (Vienna) to unlock the secrets of "strange metals". Now a breakthrough has been achieved. The results have been published in "Science".

Superconductors allow electrical current to flow without any resistance - but only below a certain critical temperature. Many materials have to be cooled down...

Im Focus: Programmable nests for cells

KIT researchers develop novel composites of DNA, silica particles, and carbon nanotubes -- Properties can be tailored to various applications

Using DNA, smallest silica particles, and carbon nanotubes, researchers of Karlsruhe Institute of Technology (KIT) developed novel programmable materials....

Im Focus: Miniature double glazing: Material developed which is heat-insulating and heat-conducting at the same time

Styrofoam or copper - both materials have very different properties with regard to their ability to conduct heat. Scientists at the Max Planck Institute for Polymer Research (MPI-P) in Mainz and the University of Bayreuth have now jointly developed and characterized a novel, extremely thin and transparent material that has different thermal conduction properties depending on the direction. While it can conduct heat extremely well in one direction, it shows good thermal insulation in the other direction.

Thermal insulation and thermal conduction play a crucial role in our everyday lives - from computer processors, where it is important to dissipate heat as...

Im Focus: Fraunhofer IAF establishes an application laboratory for quantum sensors

In order to advance the transfer of research developments from the field of quantum sensor technology into industrial applications, an application laboratory is being established at Fraunhofer IAF. This will enable interested companies and especially regional SMEs and start-ups to evaluate the innovation potential of quantum sensors for their specific requirements. Both the state of Baden-Württemberg and the Fraunhofer-Gesellschaft are supporting the four-year project with one million euros each.

The application laboratory is being set up as part of the Fraunhofer lighthouse project »QMag«, short for quantum magnetometry. In this project, researchers...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

11th Advanced Battery Power Conference, March 24-25, 2020 in Münster/Germany

16.01.2020 | Event News

Laser Colloquium Hydrogen LKH2: fast and reliable fuel cell manufacturing

15.01.2020 | Event News

„Advanced Battery Power“- Conference, Contributions are welcome!

07.01.2020 | Event News

 
Latest News

New self-assembled monolayer is resistant to air

22.01.2020 | Life Sciences

Ultrafast camera takes 1 trillion frames per second of transparent objects and phenomena

22.01.2020 | Power and Electrical Engineering

Mosquitoes are drawn to flowers as much as people -- and now scientists know why

22.01.2020 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>