It is good to be cautious (but optimistic) about cancer and heart attack vaccines

A few days ago, an interview by Guardian to the head of the medical division of Moderna triggered a wave of communication which, after a few days, also reached our country. The Guardian in fact he titled it like this: “Cancer and heart disease vaccines ready by end of decade”, and all the newspapers that I managed to read in our country took up roughly the same text, like the Republicwhich was entitled “Vaccines against cancer and heart attacks: the revolution with RNA”.

Now, for anyone who understands a minimum of medicine or biology, this is rather curious, because while it has been clear for decades what is meant by cancer vaccines, the idea that an immune response can be induced against a specific antigen to correct non-oncological or infectious cardiovascular diseases sounds somewhat new. After all, reading the text of the original interview, there is ample discussion on the potential applications of RNA vaccines in the oncological field, but no clue as to what is meant by a possible vaccine to be used in the cardiovascular field. The reason is simple: whoever collected the interview on the Guardianand from what I almost always read, even those who then relaunched it in national newspapers, must not really have very clear ideas, which is why I believe some additional explanations are due to the readers.

Let’s start with cancer: in February, the FDA granted Moderna and Roche a “breakthrough therapy designation” for the combined use of a monoclonal antibody from Roche (Pembrolizumab) and a new RNA vaccine from Moderna against advanced melanoma, in those patients who, after resection, have a high probability of recurrence and death. Compared to the monoclonal antibody alone, the addition of the vaccine decreased the risk of an inauspicious outcome by over 40 percent: an excellent result, due to the combined “cleaning” action performed by the antibody and immune-mediated induction of memory from the vaccine.

The vaccine has been used in combination with a therapeutic agent because, in many cases, cancers are specific immunosuppressants, managing to modulate the immune system so as to prevent it from mounting an adequate response to destroy them; by giving preformed antibodies, this action is at least momentarily interrupted, so that the immune system can build an effective memory response and prevent tumor regrowth (which occurs whenever even a few cells survive a therapeutic agent such as a monoclonal antibody).

The advantage of using an RNA, in the case of oncological vaccines, is crucial: since it is possible to personalize the induced antigen, the vision that researchers propose, both in Moderna and elsewhere, is that taking a biopsy from the patient, associated with tumor DNA sequencing and identification using advanced bioinformatics techniques of a specific antigenic profile of that patient’s tumor, allows the production of a corresponding vaccine RNA, which is then administered using the same technology seen in action in the last three years, or its further and improved variants.

In other words, the information needed to make it recognizable to the immune system is extracted directly from the cancer, thus circumventing the “tricks” implemented by the tumor precisely to avoid this recognition. Of course – and I ask everyone to pay attention to this point – cancer is a Darwinian system, and therefore it can respond adaptively to the selection made by the immune system; this may mean that, from time to time, further doses of RNA adapted to the recurrences that may occur will be necessary. Thus far, therefore, we are really discussing a vaccination approach to RNA; on the other hand, the method proposed to deal with some cardiovascular pathologies is completely different, which does not involve the immune system in any way and, therefore, does not correspond to the use of any vaccine – to the chagrin of the titlists of the Guardian and of our own.

Also in this case, Moderna has reached an agreement with another large pharmaceutical company, and precisely with Astra Zeneca, and also in this case limited phase II data is available (since 2021) for an RNA molecule to be injected directly into the myocardium of patients with coronary artery disease and subsequent heart failure. In this case, the RNA used encodes a protein known as Vegf-a, which is used to promote revascularization and thus increase perfusion of the ischemic heart. The very first, few clinical data presented in 2022 show a moderate, encouraging benefit of cardiac function in treated patients compared to control patients, but the statistic is really based on samples too small to be able to draw anything more than an omen; the real solid data are those in animals, where extensive revascularization has been demonstrated in accompaniment to functional recovery.

Let’s sum up: on closer inspection, and even discounting the blunder of those who spoke of vaccines for cardiovascular diseases, we are dealing with a legitimate corporate communication and certainly well motivated by the magnificent scenarios that technology opens up to Rna, but, as often happens in these cases, we are in the absence of data that provide new indications with respect to what was already heard months or years ago. Optimism and caution are therefore both well motivated, and their combination is a must.