Personalized cancer therapy vaccine wins Pfizer award

While conventional treatments such as chemotherapy and radiotherapy show their limitations in battling certain advanced cancers, immunotherapy and therapeutic vaccines have opened up a new realm of hope for patients. The underlying principle is that they mobilize the body's natural defenses to target tumor cells. Despite spectacular results in some cases, the complexity of tumors and the heterogeneity of immune profiles complicate the development of immunotherapy. In recent years, many attempts at therapeutic vaccines have failed to combine the tumor cells of patients with an effective stimulation of the immune system.

A new study has successfully tackled this double limitation. It was conducted by Prof Nicolas Mach, Head of the Clinical Research Unit of the Department of Oncology, Head of the Cancer Center at the HUG and Associate Professor at the Department of Medicine and the Translational Research Center in Onco-Hematology (CRTOH) of the UNIGE Faculty of Medicine; Rémi Vernet, Scientific Officer at the UNIGE Medicine Department; and Dr. Eugenio Fernandez, Staff Physician, Division of Oncology at the HUG. The findings are published in Cancer Research Communications, and the study has won the Pfizer award.

A two-pronged therapeutic technology

The technology the team developed, called MVX-ONCO-1, is a therapeutic vaccine that combines two complementary processes. First, a tumor sample is taken from the patient through minimally invasive surgery. The extracted tumor cells are then irradiated to render them inactive while preserving all their antigens—molecules that allow the immune system to recognize cells as foreign and destroy them.

This extract is then reinjected as a personalized vaccine. "When treating cancer, we don't always know the exact antigens to target. By using the entire inactivated tumor, we provide the immune system with a complete blueprint of possible targets," explains Vernet.

In parallel, biocompatible capsules containing genetically modified human cell lines are implanted under the skin. These encapsulated cells continuously and stably release an immune-stimulating factor, called an adjuvant, at the site of vaccination to stimulate, recruit and activate antigen-presenting cells of the immune system.

"Essentially, this immunostimulatory factor helps to rearm the immune system, particularly when it has been weakened by previous treatments such as chemotherapy. Moreover, in preclinical studies, our adjuvant has proven to be the most effective ever developed for directing the immune system against a tumor," says Dr. Fernandez.

First promising clinical results

In this first clinical study on humans, the researchers and their team treated 34 people with advanced solid tumors that were resistant to all other treatments. Each person received six injections of their own MVX-ONCO-1 vaccine over a period of nine weeks. All stages, from sampling to production and administration of the treatment, were carried out using the HUG infrastructure.

"We were able to rely on the platform of the cell therapy and transplantation laboratories of the HUG for the preparation of therapeutic cell products according to the very strict Swissmedic standards and the Research Unit of the Division of Oncology, for the management of patients and the clinical trial," emphasizes Prof. Mach.

More than half of the study participants showed signs of clinical benefit, ranging from stabilization of the disease to prolonged survival. No significant side effects were observed. "For patients, this is a minimally invasive and very well-tolerated therapy. This is essential when you consider how taxing conventional treatments can be," says Dr. Fernandez.

Toward a new generation of therapeutic cancer vaccines

While the results of the study are not yet proof of effectiveness on a large scale, they lay the foundation for a fully personalized therapeutic strategy.

"There is still much work to be done. We now need to test this technology in larger cohorts, at earlier stages of the disease and combine it with other existing treatments. But we are starting from a solid base," says Nicolas Mach. "The next step will be securing funding. Advanced-phase clinical trials require very significant resources. Winning the Pfizer Prize is an important milestone, a mark of excellence and recognition that will help attract the necessary support to allow us to move forward."

More information:
Rémi Vernet et al, A First-in-Human Phase I Clinical Study with MVX-ONCO-1, a Personalized Active Immunotherapy, in Patients with Advanced Solid Tumors, Cancer Research Communications (2024). DOI: 10.1158/2767-9764.crc-24-0150

Provided by Geneva University Hospitals