Linfociti T multi-virus specifici per il trattamento delle infezioni virali post trapianto

Abstract

Infusion of virus-specific T lymphocytes represents a valid alternative therapeutic strategy to conventional anti-viral drugs for the treatment of virus-related complications in organ transplanted patients. In order to increase the clinical potential of this cell-based immunotherapy, we are developing in our research laboratories innovative approaches to generate and select specific multi-virus T clones.

The T lymphocyte clones, generated from healthy donors’ blood, are activated in vitro against Epstein-Barr virus (EBV), Cytomegalovirus (CMV), Adenovirus (ADV), BK Poliomavirus (BKV) and Herpesvirus-8 (HHV-8) using a mixture of immunodominant and interleukin viral peptides.

The creation of a multi-virus specific heterologous T lymphocytes bank, which is our final objective, would guarantee the availability of a “ready-to-use” product: multi virus specific T cells, derived from a donor who is compatible in terms of major HLA histocompatibility, to be infused into the patient when a post-transplant virus-related complication is diagnosed.

Impact:

Infectious disease, particularly those caused by viral agents, are the main cause of post-transplant morbidity and mortality. Up to 75% of transplanted patients develop infections during the first year after transplantation. The primary cause of this phenomenon is the inhibition of the cell-mediated virus-specific immune response induced by the immunosuppressant drugs used to prevent rejection. Since T cells play a key role in the control and clearance of viral infections, the state of immunodepression promotes primary infection, reinfection or reactivation of viral agents with high prevalence, such as herpes viruses (eg EBV, CMV and HHV-8), with possible development of systemic or organ diseases. The treatment of these infections is a significant challenge because of the scarcity of antiviral drugs and their associated toxicity. An alternative treatment, now clinically validated, is the infusion of virus-specific T lymphocytes, an advanced Therapy Medicinal Product (ATMP) that enables the patient to develop in vivo a cytotoxic response against infected cells: an effective therapy both as a prophylaxis and as cure of virus-induced pathological manifestations which could be lethal for the patient.

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