This is how we reprogram our cells to fight cancer

Car-Ts are one of the most innovative and discussed developments in oncology today. The result of almost 40 years of research, and landed on the pharmaceutical market just seven years ago, they are a form …

This is how we reprogram our cells to fight cancer

Car-Ts are one of the most innovative and discussed developments in oncology today. The result of almost 40 years of research, and landed on the pharmaceutical market just seven years ago, they are a form of gene therapy that allows the patient’s immune system to be recruited to counteract the development of tumors. They promise to treat onco-haematological tumors against which all other lines of therapy fail, but with staggering prices, and long-term efficacy and safety still to be discovered, given that their diffusion in the clinic is still very recent. A promising field, in short, in which research is extremely lively and which sees our country at the forefront: in recent days, in fact, the news of the authorization provided by Aifa for the production of Car-T in the Immuno-Gene Therapy Factory of the Romagna Institute for the Study of Tumors (IRST) ‘Dino Amadori’ in Meldola, which thus becomes the third Italian research center (and the first in Romagna) dedicated to the study and clinical development of these revolutionary therapies. Let’s see what this could mean for patients.

Car t

Car-T is a form of immunotherapy based on gene therapy. It therefore aims to activate the cells of our immune system, in this case the T lymphocytes, to hunt for tumor cells and destroy them. To do this, lymphocytes are taken from the patient and modified in the laboratory using genetic engineering techniques, so that they express a class of synthetic anti-tumor receptors known as chimeric antigen receptors (Car, in fact, in Car-T), which combine the ability to activate T lymphocytes and direct them towards a target (or rather an antigen) present on the membrane of the tumor cells.

In practice, the therapy begins with a sample with which the patient’s T lymphocytes are collected, then continues in the laboratory where they are engineered to express the Car receptors and then “expanded” to obtain millions of copies of the new synthetic lymphocytes, and ends in hospital, where they are reinfused so that they hunt for tumor cells. The process is evidently laborious, and therefore expensive, with prices exceeding 300-400 thousand euros per patient, but it offers otherwise impossible results in the case of recurrent tumors, for which the therapeutic options would be practically nil. The commercial development of these therapies has led in recent years to the rapid approval of six Car-Ts starting from 2018 (the first arrived in Italy in 2019) aimed at the treatment of patients suffering from lymphoma, acute lymphoblastic leukemia and myeloma, and at development of a network of clinical centers which now includes 31 institutions authorized for administration throughout Italy. The results, as we said, are promising (in some cases astonishing), but there are problems.

Duration, toxicity and costs

CAR-Ts currently show surprising results, especially in patients in the advanced stages of the disease, who have not responded to standard therapies and for whom the therapeutic options would otherwise be very limited, as well as the chances of survival. For lymphomas and acute lymphoblastic leukemia, they allow many patients to eliminate the disease with such effectiveness that we are now starting to talk about recovery, even if the follow up is still too short to be certain about its duration over time. For myeloma, the efficacy has not yet proven to be so powerful, but in many patients they still allow the disease to be kept at bay for a long time, in phases in which otherwise it would no longer be possible to intervene.

Unfortunately, currently approximately 50% of patients who are treated with CAR-T are destined to experience a recurrence. These therapies are also burdened by serious side effects, even potentially lethal, and by the risk (currently considered very low) of inducing the appearance of secondary tumors. The methods of personalizing therapies also require relatively long times for access, because patients must be followed in authorized clinical centers and their T lymphocytes must be sent to the laboratories of pharmaceutical companies to be engineered, and therefore several weeks pass before they are sent back to infusion centers. Furthermore, currently this technology has proven to be effective only against some specific subgroups of hematological neoplasms, and still completely ineffective in the case of solid tumors.


Despite being the result of decades of research, Car-Ts are a field that is still in its infancy. They still have to demonstrate in the field that they are fully worth the enormous economic and organizational investment they are asking of healthcare systems, and that they can treat a wider range of patients than the current one. This is why it is important to continue doing research. “We are currently among the very few laboratories authorized for the production of genetically modified lymphocytes, together with the Bambino Gesù of Rome and San Gerardo of Monza”, explains Massimo Petrini, director of the Immuno-Gene Therapy Factory of the Romagna Institute for the study of tumors. “We are now working on developing protocols for phase 1 and 2 studies for testing Car-Ts in the oncology-hematology field, and there are many aspects of these therapies that we aim to investigate in the coming months and years.”

The most interesting aspects of the research, Petrini explains, are trying to improve the persistence of genetically modified cells in the organism, and therefore their effectiveness; reduce toxicities related to treatment, even using other drugs; the search for new molecular targets, with which we can perhaps also effectively target solid tumors. There are also many other types of cell therapies under study, such as Car-Cik or therapy with tumor-infiltrating lymphocytes, which are giving promising results and which could see the light of day in the clinic in the next few years. “Advanced therapies are a field of study in full swing – concludes Petrini – and having more laboratories capable of producing them and carrying out trials for Italian patients will mean having access to more clinical trials, and therefore more treatment opportunities, and also greater proximity which will speed up the time it takes to obtain therapies, and will make them more economically sustainable”.