Immunisation against infections has become, for most of us, a routine part of life. The general principle is familiar. Expose the body to harmless fragments (antigens) from disease-causing viruses or bacteria and our immune system will produce antibodies and white blood cells (T cells) to attack what it recognises as foreign material. Should we subsequently encounter the actual microorganism, our defences have a vital head start in neutralising the threat. Vaccination protects against a wide variety of serious infections, from meningitis to measles, tetanus to polio. And, most recently, severe Covid disease.
But might we be on the threshold of a new era in which vaccines will help in the fight against cancer? That was the suggestion made by professors Uğur Şahin and Özlem Türeci, co-founders of the German company BioNTech, during an interview with the BBC’s Laura Kuenssberg on 16 October. Over the past two years, BioNTech has gone from obscure biotechnology outfit to near-household name thanks to its partnership with the US pharmaceutical giant Pfizer in creating one of the world’s most successful Covid vaccines. Far from resting on their laurels, Şahin and Türeci suggested to Kuenssberg that by 2030 they may have transformed their technology into a weapon to be deployed against malignancy.
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This may seem a startling claim, but it sits squarely within a new area of cancer therapeutics that has been gathering momentum over the past decade: immunotherapy. Medics have long suspected that our immune system plays a vital role in protecting against malignancy. Transplant patients, for example, given powerful drugs that suppress their immune systems in order to prevent organ rejection, are prone to developing tumours. Equally, population-screening programmes like breast mammography, aiming to detect cancer at an early stage before symptoms develop, pick up many more malignancies than would be expected from the incidence of clinical disease. The inference is that, in many cases, cancers that arise within our bodies are controlled or even eradicated by an immune response before they can cause us harm.
Why and how do some malignancies escape our bodies’ defences? Beyond immunosuppression (whether due to medication, ageing, severe stress, or other factors) there seem to be two broad explanations. First, many cancers acquire mutations that enable them to switch off or circumvent immune system responses that would otherwise make them vulnerable to attack.
The second impediment to successful immune system control is that cancers comprise altered human cells. While viruses and bacteria are readily recognised as “foreign” by our innate defences, tumour cells share many characteristics with normal tissues, effectively camouflaging them. And surface antigens that do mark them as abnormal can vary in different regions of a tumour, presenting a shifting target.
This is where vaccination may come in. Molecular analysis of cancers is increasingly sophisticated, enabling pathologists to “type” tumours according to the abnormal antigens expressed on their cell surfaces. There are already many therapies that deploy lab-created “monoclonal” antibodies that bind to these cancer antigens and so stimulate immune system attack. BioNTech’s vision is for vaccine technology to stimulate patients’ defences to generate effective antibody and T cell responses from within the body itself.
The Pfizer-BioNTech Covid vaccine employs novel messenger RNA (mRNA) technology. This mRNA is a short-lived genetic material that contains the instructions for cells to synthesise a particular protein – in the case of the Covid vaccine, the surface “spike” that the virus uses to enter our tissues. The large amount of spike protein produced in the days following immunisation creates a strong immune reaction, and if the Covid virus is subsequently encountered it is neutralised before it can cause severe infection. Now that this new technology has become established, any mRNA could, in theory, be substituted. BioNTech envisages a time when a particular patient’s tumour could be typed, and corresponding mRNA vaccines administered that would provoke a vigorous response against antigens on the cancer cells’ surfaces.
Professors Şahin and Türeci have been careful to emphasise that there are many problems that need to be overcome. A different form of immunotherapy, “CAR T”, in which a patient’s T cells are genetically modified to attack certain types of blood-cell malignancy, can provoke catastrophic side-effects as a result of unbridled immune system activity. And the microenvironment within many solid tumours poses additional challenges to an effective immune response.
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BioNTech has reported encouraging results in some early trials, but we are still very far from a time when vaccination against cancer might become routine. So why go public now? Covid presented BioNTech with an extraordinary windfall, with billions in revenue from its partnership with Pfizer. The German firm has reinvested huge sums to accelerate its work on cancer therapeutics, but projections for the next few years show diminishing revenues from Covid vaccine sales. Maintaining momentum will require external investment. The BBC interview was well-intentioned, but like all announcements of an imminent breakthrough without an actual breakthrough to announce, it would partly have been done to help secure future funding.
Immunotherapy continues to offer exciting prospects in the battle against our old foe, cancer. But the costs of progress are high, and hype and hope remain intrinsically uneasy bedfellows.
Phil Whitaker’s new book, “What Is a Doctor?”, will be published by Canongate in July 2023
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This article appears in the 19 Oct 2022 issue of the New Statesman, State of Emergency