09 March 2020

The “immunological memory” of common childhood vaccines could be exploited to boost the effectiveness of cancer vaccines, according to a research team in Finland.

The research, published in the journal Cancer Research, was led by Professor Vincenzo Cerullo of the University of Helsinki. They found that animals that were pre-immunised with an ordinary vaccine, such as the tetanus virus, responded better to cancer vaccine treatment for an engrafted tumour.

The authors explain that therapeutic cancer vaccines generate an anti-tumour response more similar to a primary than a secondary immune response. In order to convert this into a secondary response, the team developed their hybrid tumour-pathogen therapeutic cancer vaccine.

Mice carrying melanoma tumours were initially vaccinated against tetanus, and were then treated with a new hybrid viral platform called PeptiCRAd (Peptide-coated Conditionally Replicating Adenovirus). In their initial experiments, the adenovirus displayed peptides relating to both melanoma and tetanus antigens. This led to a dramatic improvement in the mice’s immune response to the tumour, compared with a virus which only displayed tumour peptides.

The immune response in pre-immunised mice was also superior to that in unvaccinated animals. This indicates that it is the pre-existing immunity to tetanus that supported the anti-tumour effect.

The researchers then repeated the experiments with mice vaccinated against different human diseases, showing that potentially any peptide which reactivates the memory T cells in these mice can also boost the anti-tumour response caused by PeptiCRAd. Combining their vaccine therapy with immune checkpoint inhibitors led to even greater response in their mouse model.

Prof Cerullo believes that this approach can be very easily translated into clinical trials, as it relies on pre-existing immunity of vaccines included in national vaccination programs worldwide.

“This method has potential to have a significant impact on current immunotherapy protocols,” Prof Cerullo says. “Since their introduction, the vaccines have made one of the greatest contribution to public health, with the eradication of common deadly infections such as smallpox. We thought that they could do even more and help our fight with the cancer.

“We decided to modify the well-established PeptiCRAd platform by adding another set of peptides derived from pathogens, which patients have been vaccinated for e.g. tetanus or diphtheria,” says Cerullo.

Co-author Dr Sara Feola adds: “The main idea is to take advantage of the pre-existing pathogen-specific immunological memory present in the worldwide population of vaccinated individuals. This boosts the anti-tumour response, directing pre-existing memory T cells towards the tumour.”


Source: Tähtinen S, Feola S, Capasso C, Laustio N, Groeneveldt C, Ylösmäki EO, Ylösmäki L, Martins B, Fusciello M, Medeot M, Tagliamonte M, Chiaro J, Hamdan F, Peltonen K, Ranki T, Buonaguro L, Cerullo V (2020) “Exploiting the pre-existing immunity to enhance oncolytic cancer immunotherapy”, Cancer Research, doi: 10.1158/0008-5472.CAN-19-2062

 

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