Primo vaccino 2.0 a Dna per la cura del tumore al pancreas

Aiutaci a cambiare il destino del tumore al pancreas.

Il tumore del pancreas è una delle malattie oncologiche più letali, con un tasso di sopravvivenza ancora troppo basso. Colpisce sempre più persone tra i 40 e i 50 anni, e si stima che entro il 2030 sarà la prima causa di morte per tumore. Oggi, però, abbiamo un’opportunità concreta: una sperimentazione per un vaccino terapeutico somministrabile a tutti i pazienti che potrebbe rivoluzionare la lotta contro questa malattia. Abbiamo bisogno del tuo aiuto per avviare questa sperimentazione in Italia.

Ogni donazione alla fondazione può fare la differenza. Sostieni la ricerca. Dai speranza a migliaia di persone. Il progetto è coordinato da Francesco Novelli, Professore Ordinario di Immunologia e Direttore del Dipartimento di Biotecnologie Molecolari e Scienze per la Salute dell’Università di Torino.

Help us change the future of pancreatic cancer.

Pancreatic cancer is one of the deadliest cancers, with a survival rate that remains devastatingly low. It increasingly affects people as young as 40 or 50, and by 2030, it is expected to become the leading cause of cancer-related death. But today, we have a real chance: a clinical trial for a therapeutic vaccine for all patients that could revolutionize how we fight this disease. We need your support to launch this trial in Italy. Every donation can make a difference. Support research. Bring hope to thousands. The project is coordinated by Francesco Novelli, Professor of Immunology and Director of the Department of Molecular Biotechnology and Health Sciences at the University of Turin.

Prof. Novelli’s Laboratory Project: Towards Clinical Trials for the Treatment of Pancreatic Cancer

In the last ten years, our laboratory has developed preclinical models of pancreatic cancer for an immunotherapeutic treatment based on a DNA vaccine targeting the alpha-enolase protein. The idea stems from the observation that patients with pancreatic cancer who showed high levels of specific antibodies against alpha-enolase at diagnosis generally had a much better life expectancy than others.

The vaccine mechanism primarily works through the stimulation of antibodies and not only that. In fact, the DNA vaccine awakens and expands immune cells with antitumor activity and reduces those immunosuppressive populations typical of pancreatic cancer. All these responses induced by the vaccine effectively act to increase the patient’s life expectancy.

To date, surgical resection is feasible in only a small percentage of patients, so chemotherapy unfortunately remains the only available therapy for the majority. Despite various efforts to find new chemotherapeutic drugs or combinations thereof, clinical studies have shown only limited benefits in survival, with obvious side effects due to high toxicity. On the contrary, immunotherapy, as an antitumor strategy, is proving effective in many tumors with limited side effects. Our recent studies show that combining the vaccine with chemotherapy may be a valid strategy to treat pancreatic cancer more effectively. This combination enhances the vaccine’s effectiveness in reducing tumors and lesions by activating more anti-tumor immune cell populations than the vaccine alone.

In fact, we recently demonstrated that chemotherapy-treated patients showed an increase in alpha-enolase-specific immune responses, while some patients who did not respond to the vaccine alone began to respond when chemotherapy was added. The results of this important work have just been accepted for publication in the journal Journal of Immunotherapy of Cancer (Mandili et al., JITC 2020). The combination significantly slowed tumor progression and increased lymphocyte influx into the tumor itself. Moreover, the same study showed that chemotherapy increases the antibody response not only against alpha-enolase but also towards other molecules. These potentially new targets are currently in preclinical testing to evaluate their role in the antitumor response that could be achieved with a multi-target vaccine, always in combination with chemotherapy.

Secondly, we have completed the necessary preclinical testing for the approval of the DNA vaccine as a drug to be administered to patients. Therefore, our next goal is to draft the required documents for approval by the Italian Medicines Agency (AIFA). In fact, no currently approved study uses this type of drug, and AIFA authorization remains a mandatory step before proceeding with procedures toward clinical trials.

The clinical testing of the vaccine, particularly Phase 1 trials — which will provide an initial assessment of the drug’s safety and tolerability — will be carried out in collaboration with oncologists from COES (Oncology and Hematology Center of Città della Salute e della Scienza) as part of a nonprofit study protocol (not sponsored by any pharmaceutical company).

At the moment, procedures are underway to obtain AIFA authorization for the creation and launch of a Phase 1 unit within the COES. The project is coordinated by Dr. Rosella Spadi. Unless delayed by the new wave of the SARS-CoV2 epidemic, the process should conclude by the first half of 2021. The Molinette Research Foundation will contribute to purchasing necessary equipment (refrigerated cabinet for biological sample storage, beds, and other equipment) for the Phase 1 Unit.

The health emergency caused by the SARS-CoV-2 pandemic has significantly impacted the work of the entire University of Turin, which had to suspend not only in-person classes but also research activities. In particular, our research group had to suspend all animal experiments because staff were only allowed access to research labs for essential treatments or improbable reasons. Despite the suspension of lab activities, which had a significant impact on researchers’ workflows, we actually never stopped. We continued scientific activities without a lab bench, focusing more on data analysis, writing, and discussing collected results, as well as studying published works to design and organize new experimental strategies for future funded research.

We remind that Phase 1 trials aim to provide an initial assessment of the safety and tolerability of new drugs, in this case a DNA vaccine administered to patients in combination with standard chemotherapy. This implies further efforts in the coming year to demonstrate feasibility and non-toxicity in new preclinical models, involving specialized laboratories tasked with conducting experiments using the final vaccine formulation, produced according to Good Manufacturing Practice (GMP) standards.

Finally, studies continue to develop essential laboratory tools to track the immune response induced by the vaccine in patients enrolled in clinical trial.