Zalmoxis® is a patient-specific cell therapy based on the engineering of the immune system that, in association with haplo-identical hematopoietic stem cell transplantation, allows the treatment of adult patients with leukemia and other high-risk haematological malignancies.
Chemotherapy is currently the main therapeutic strategy for patients with leukemia. Once subjected to chemotherapy cycles, the patient's hematopoietic and immune system is strongly debilitated. In order to favor its regeneration, we proceed to the transplantation of hematopoietic stem cells from a partially compatible donor. However, the transplant-borne stem cells need time to differentiate into the mature cells of a fully functional immune system. In this window, the patient is defenseless against both infections and possible leukemic relapses.
In the case of a perfectly compatible donor, the necessary immune defenses are provided by the donor's T lymphocytes. However, in the case in which the compatibility between patient and donor is only partial, the lymphocytes of the latter can not be used because they would involve a very high risk of developing the "graft versus host disease" (Graft versus Host Disease, GvHD ), in which the cells transplanted from the donor attack the tissues of the transplanted patient, with often lethal results.
The therapeutic advantage introduced by Zalmoxis® lies in the shelter of the protective action of the donor's T cells, even if the patient-donor therapy is only partial. Zalmoxis® is based on the use of genetically modified T lymphocytes in which a "suicide gene" (HSV-TK) has been inserted. These cells, once infused in patients undergoing non-compatible donor hematopoietic stem cell transplantation, facilitate the anti-leukemic and anti-viral effect. Furthermore, reimbursement to post-transplant immunosuppressive prophylaxis is no longer necessary and immunological reconstitution is faster. The insertion of the suicide gene allows to control the appearance of the first symptoms, because the lymphocytes in the rejection reactions can be selectively eliminated thanks to the administration of ganciclovir, a common antiviral drug that in combination with the suicide gene induces the death of the cells involved in the GvHD.
Thanks to this mechanism Zalmoxis® demonstrated, in the retrospective pair matched analysis that led EMA to grant the Conditonal Marketing Authorization (CMA,), a significant increases in long-term patient survival,