University of Basel-Led Preclinical Team Develops Novel Combination of Antibodies to Improved Cancer Immunotherapy Results

University of Basel-Led Preclinical Team Develops Novel Combination of Antibodies to Improved Cancer Immunotherapy Results

University of Basel, Switzerland researchers and oncologists have recently published the summary of a preclinical animal model-based study that showcases the simultaneous use of antibodies based on two differing mechanisms of action led to more effective destruction of tumors. The hypothesis moving forward: Patients not responding to current immunotherapy options could benefit most from this new treatment. A collaborative effort leveraged anti-angiogenetic antibodies from Roche.

Immunotherapies Boosted with Combinations

With the results recently published in the scientific journal PNAS, the Swiss team reminded readers that research has made great strides in the past few years with immunotherapies targeting cancer. Novel therapies are used to recruit the body’s own immune system to destroy cancerous tissue. An antibody activates the CD40 receptor on the surface of the immune cells and hence stimulates the production of natural killer T-cells.

But the success of the CD40 antibody fell short of expectations as less than 20% of patients have responded. The Swiss-based team out of University of Basel has demonstrated via animal models that the effect of the anti-CD40 antibody can be significantly boosted by combining it with two other antibodies that attach to tumor blood vessels.

Invading the Tumor via the Blood Vessels

Apparently, the administration of the anti-CD40 antibodies lead to an increase in killer T-cells as intended however they can only be detected in the peripheral areas and not in the interior of the tumor. The team believed that this was the result of the nature of the tumor’s 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 of the antibodies were provided by biopharmaceutical company Roche.

The Results

The team implemented the approach based on their hypothesis of the problem. They then tested the new combination of antibodies in several animal models for different cancers from colorectal and breast to skin cancer. The combination of the three antibodies significantly improved tissue destruction in all cancers. The addition of the two Roche anti-angiogenetic antibodies ensured the tumors had more intact blood vessels. 

Unexpectedly, these investigations also revealed that the antibody combination very effectively strengthens the immune system in a number of ways, including through a better penetration of the tumor by killer cells and by promoting a tumor-hostile inflammatory reaction in the tumor microenvironment.

Investigator Comment

Dr. Kashyap noted how important an understanding of the biology of tumors actually is and suspects that patients with ‘cold’ tumors—that is tumors that do not respond well to immunotherapy—could benefit most from this new combination. He commented, “the anti-angiogenetic antibodies may make the ‘cold’ tumors ‘hot,’ so that immunotherapy functions better.”

Cooperation in Pursuit of Medical Advancement

This study success was the direct result of the coming together of dedicated and committed professionals in various fields of research. Several research groups agreed to cooperate so that the various results could be verified by others. For example, experiments were carried out at the University Hospital Basel, EPFL and the Roche Innovation Center in Zurich. The same results were also confirmed by Alfred Zippelius, Professor of Translational Oncology at the University of Basel and senior author of the study.  Zippelius noted, “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.”

Lead Research/Investigator

Alfred Zippelius, Professor of Translational Oncology at the University of Basel

Dr. Abhishek Kashyap 

Call to Action: Several early clinical trials of similar therapies in humans are underway.