A research team at the Medical University of Vienna led by Maria Sibilia has investigated a new combination therapy against cancer.

This therapy employs systemic administration of the tissue hormone interferon-I combined with local application of Imiquimod.

This combination showed promising results in topically accessible tumours like melanoma and breast cancer models: The therapy led to the death of tumour cells at the treated sites and simultaneously activated the adaptive immune system to fight even distant metastases.

The results published in the top journal Nature Cancer could improve the treatment of superficial tumours such as melanoma and breast cancer.

In recent years, immunotherapies have had significant success in the treatment and cure of a wide range of cancers.

However, for some patients, these agents are still not sufficiently effective.

As part of a preclinical study, Maria Sibilia, Head of the Centre for Cancer Research at the Medical University of Vienna, therefore investigated the effects of a combination immunotherapy consisting of systemic administration of the tissue hormone interferon (IFN)-I and local imiquimod therapy.

Imiquimod is an active substance that activates the innate receptors TLR7/8 and used to treat basal cell carcinomas.

The researchers employed various preclinical mouse tumour models of melanoma and breast cancer.

What both tumours have in common is that they are accessible to local therapy and often form distant metastases.

Effective for local tumours and distant metastases

Immunotherapies use the body's own immune system to fight cancer cells.

Plasmacytoid dendritic cells (pDCs), which are activated by Imiquimod via TLR7/8, play an important role in this process.

The study showed that oral imiquimod stimulates pDCs to produce the tissue hormone IFN-I.

This sensitised other dendritic cells and macrophages in the tumour environment to topical imiquimod therapy, which inhibited the formation of new blood vessels via the cytokine IL12 leading to the death of tumour cells.

The combination immunotherapy not only had an effect on the treated tumours, but also on distant metastases.

It reduced the formation of new metastases thus preventing tumour relapses and increasing the sensitivity of melanomas to checkpoint inhibitors.

“These findings illustrate that the combination of systemic treatment with imiquimod or IFN-I and topical therapy with imiquimod has the potential to expand treatment options for patients and improve therapy outcomes in locally accessible tumours such as melanoma or breast cancer,” emphasises Maria Sibilia.

“Topical treatment of the primary tumour with imiquimod is essential for this combination therapy with systemic IFN-I to be effective at the treated site and also to clear distant metastases,” adds Philipp Novoszel, MedUni Vienna, one of the first authors of the study.

The results suggest that this therapeutic strategy has the potential to improve treatment outcomes in superficial and thus locally accessible tumours such as melanoma and breast cancer - on the one hand through therapy-associated cancer cell death at the locally treated tumours, but also through the induction of a T cell-induced anti-tumour immune response at distant metastases, which is further enhanced by checkpoint inhibitors.

“Our aim is to continue developing immunotherapeutic strategies in order to improve the long-term prospects for patients who are not yet responding well to these agents,” says Maria Sibilia, who is also Deputy Head of the Comprehensive Cancer Centre of MedUni Vienna and University Hospital Vienna.

“As systemic interferon is a well-known cancer therapy and dendritic cells are activated in a similar way to our preclinical models, we believe that the new combination therapy can show an effect in patients,” adds Martina Sanlorenzo, dermato-oncologist at MedUni Vienna and co-first author of the study.

Source: Medical University of Vienna