Adoptive Transfer of JC Virus-Specific T Lymphocytes for the Treatment of Progressive Multifocal Leukoencephalopathy.

Affiliation

Berzero G(#)(1)(2), Basso S(#)(3)(4), Stoppini L(3)(4), Palermo A(1), Pichiecchio A(2)(5), Paoletti M(5), Lucev F(5), Gerevini S(6), Rossi A(7), Vegezzi E(1)(2), Diamanti L(1), Bini P(1), Gastaldi M(1), Delbue S(8), Perotti C(9), Seminari E(10), Faraci M(11), Luppi M(12), Baldanti F(13), Zecca M(4), Marchioni E(#)(1), Comoli P(#)(3)(4).
Author information:
(1)Neuroncology Unit, IRCCS Mondino Foundation, Pavia, Italy.
(2)Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
(3)Cell Factory, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy.
(4)Pediatric Hematology-Oncology Unit, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy.
(5)Neuroradiology Unit, IRCCS Mondino Foundation, Pavia, Italy.
(6)Department of Neuroradiology, Papa Giovanni XXIII Hospital, Bergamo, Italy.
(7)Neuroradiology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
(8)Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
(9)Transfusion Service, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy.
(10)Infectious Disease Department, IRCCS Fondazione Policlinico San Matteo, Pavia, Italy.
(11)HSCT Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
(12)Department of Medical and Surgical Sciences, Section of Hematology, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
(13)Molecular Virology, IRCCS Fondazione Policlinico San Matteo, University of Pavia, Pavia, Italy.
(#)Contributed equally

Abstract

OBJECTIVE: Progressive multifocal leukoencephalopathy (PML) is still burdened by high mortality in a subset of patients, such as those affected by hematological malignancies. The aim of this study was to analyze the safety and carry out preliminary evaluation of the efficacy of polyomavirus JC (JCPyV)-specific T cell therapy in a cohort of hematological patients with PML. METHODS: Between 2014 and 2019, 9 patients with a diagnosis of "definite PML" according to the 2013 consensus who were showing progressive clinical deterioration received JCPyV-specific T cells. Cell lines were expanded from autologous or allogenic peripheral blood mononuclear cells by stimulation with JCPyV antigen-derived peptides. RESULTS: None of the patients experienced treatment-related adverse events. In the evaluable patients, an increase in the frequency of circulating JCPyV-specific lymphocytes was observed, with a decrease or clearance of JCPyV viral load in cerebrospinal fluid. In responsive patients, transient appearance of punctate areas of contrast enhancement within, or close to, PML lesions was observed, which was interpreted as a sign of immune control and which regressed spontaneously without the need for steroid treatment. Six of 9 patients achieved PML control, with 5 alive and in good clinical condition at their last follow-up. INTERPRETATION: Among other novel treatments, T cell therapy is emerging as a viable treatment option in patients with PML, particularly for those not amenable to restoration of specific immunity. Neurologists should be encouraged to refer PML patients to specialized centers to allow access to this treatment strategy. ANN NEUROL 2021;89:769-779.