Oncology

From melanoma to gastrointestinal cancers: new prospects from immunotherapy

A ‘super cytokine’ designed to boost the immune system’s ability to recognise and fight cancer cells could mark a breakthrough in treatment resistance

by Paolo Ascierto *

11 November 2026

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3' min read

Translated by AI

Versione italiana

3' min read

Translated by AI

Versione italiana

One of the most significant challenges in modern oncology is overcoming resistance to treatment. In recent years, immunotherapy has profoundly changed the treatment options for numerous cancers, but not all patients respond to it and, even when it works initially, the disease can develop mechanisms that allow it to evade the immune system’s control once again. It is precisely in this area that some of the most promising research is currently being focused.

A new experimental immunotherapy, already recognised in the field of melanoma, could open up significant new possibilities for the treatment of advanced gastrointestinal cancers, even when previous treatments have failed. It is called MDNA11 and is a bioengineered molecule, described as a ‘super cytokine’, designed to enhance the immune system’s ability to recognise and fight cancer cells.

The study

The results of the international Phase 1/2 Ability-1 trial, presented at the Society for Immunotherapy of Cancer (SITC) conference in Phoenix, show that 8 out of 20 patients (40 per cent) achieved an objective response to treatment, whilst in 16 (80 per cent) the disease was found to be under control. A reduction in tumour mass was also observed in 11 out of 20 patients.

But the most surprising finding concerns liver metastases, which are particularly difficult to treat and are often associated with a poorer prognosis. In four patients treated with MDNA11 alone, all eight liver lesions examined disappeared completely. Although this result was achieved in a still very small number of people, it represents a highly promising sign for the development of new treatment options.

There are quite a few of these patients; they just seem few in number. What I mean is that every new treatment, before it can be used in everyday practice, must go through several stages of trialling. It is a long and rigorous process, but all the major therapeutic innovations we use today to treat patients have, in turn, gone through initial studies conducted on small groups of people.

It is in this context that the results of Ability-1 should be viewed; this is a trial that began several years ago and which, through successive updates, is yielding increasingly encouraging findings.

Experimental therapy

MDNA11 has been used either on its own or in combination with pembrolizumab, an immunotherapy drug already used in the treatment of various cancers. The molecule is a modified version of interleukin-2, a substance naturally involved in regulating the immune system. Thanks to bioengineering, it has been designed to selectively stimulate the immune cells capable of attacking the tumour, whilst avoiding the activation of those that might instead hinder the body’s response. The aim is therefore to reactivate the immune system even when the tumour has developed resistance mechanisms.

Another encouraging finding concerns tolerability. Among the more than 140 patients treated in total in the Ability-1 study, which also included other solid tumours, more than 90 per cent of the adverse events associated with the drug were mild or moderate in severity and generally of short duration.

Beyond gastrointestinal cancers

The prospects for this research are not limited to gastrointestinal cancers. Ability-1 is also evaluating the use of the same molecule in advanced melanoma – my own area of specialisation – a cancer in which immunotherapy has already revolutionised treatment options, but where the challenge of resistance remains. In this area too, we are seeing promising signs, which could open up new avenues for patients who no longer respond to available treatments. And we will be discussing this soon at the ‘Immunotherapy and Melanoma Bridge’ conference, to be held in Naples from 29 November to 3 December.

There is a long way to go, but this is precisely how cancer research works: through small steps, observations, tests and findings which, over time, can lead to new treatment options.

* Full Professor of Oncology, Federico II University of Naples – President of the Melanoma Foundation

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