In recent years, CAR-T cells, engineered to fight cancer, have become one of the symbols of innovation in the fight against cancer. In their classic formulation we mean T lymphocyte based therapies modified in the laboratory to recognize and attack tumor cells, once reintroduced into the patient. But revolutionary as they are, they present many obstacles to overcome. And the idea that comes today from the pages of Nature Chemical Biology aims to overcome some of these. As? By making these cells not only able to recognize and attack cancer cells, but also by transforming them into small drug factories, to be released on site, thus enhancing their overall anticancer activity.
The idea is still confined to laboratory experiments and preclinical tests but it is promising, to the point that it has already attracted the interest of a company that wants to develop the therapy and test it on a clinical level, say the researchers of the Memorial Sloan Kettering Cancer Center. of New York who developed it. In fact, it consists in doubly arming T lymphocytes: not only by equipping them with a receptor capable of recognizing and attacking cancer cells (the chimeric antigen receptor, CAR, which gives the therapy its name) but also by modifying them to carry an enzyme. This enzyme allows the maturation of a substance, injected into the circulation in an inactive form (a prodrug), into a drug: in this way the CAR-T cells can lash a double attack. On the one hand they are in fact enhanced thanks to the chimeric receptor, which recognizes a specific molecule expressed on tumor cells, on the other hand they favor the formation of an anticancer drug where it is needed, as explained by David A. Scheinberg, head of the work.
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This strategy, as mentioned, allows to partially overcome the limits associated with the use of CAR-T, until now considered a real therapeutic option only for selected cases of patients with some forms of haematological tumors. But CAR-T, not without toxicity problems, have limitations: tumors can escape the modified cells, losing the antigen against which the chimeric receptor is directed, they can also undergo the immunosuppressive effects of the tumor environment and exhaust the their immunological potential, the researchers write. A strategy that arms CAR-T cells with a second load – the enzyme for making a drug – would allow some of these limitations to be overcome. Tests in vitro and in mice have shown that these cells, renamed Seaker Cells, work.
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Seaker stands for Synthetic Enzyme-Armed KillER cells, which in Italian we could translate into synthetic enzyme-armed killer cells. These are flexible cells that could also be used in other fields. “By changing the enzyme and prodrug, it is possible to change the antitumor action. But also the action of the cells itself, directing them against autoimmune diseases or infections ”, concludes Scheinberg.
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