Project_HSCT — Lab Mavilio

Understanding the impact of the immune-reconstitution on the hematopoietic stem cell transplantation outcome

Haploidentical hematopoietic stem cell transplantation (h-HSCT) is a therapeutic option to cure patients affected by hematologic malignancies. Immune-reconstitution (IR) is critical in determining the clinical outcome of HSCT, thus a better understanding of the kinetic and quality of IR can predict opportunistic infections, tumor-relapse, engraftment and Graft versus Leukemia (GvL) and Graft versus Host Diseases (GvHD).

We previously disclosed the kinetics of Natural Killer cell (NK) IR after h-HSCT. We demonstrated the expansion of an unconventional NK subset driving the NK IR, impaired in their effector functions and expressing the inhibitory receptor NKG2A.

Based on these observations, we are now carrying on a phase II clinical trial by infusing Monalizumab, a humanized anti-NKG2A antibody, to unlock NK functions early after h-HSCT, thus promoting GvL, GvHD and preventing opportunistic infections.

TEAM

Clara Di Vito PhD - Senior staff scientist

Alessandro Frigo - Post-doctoral fellow

FUNDing

Associazione Italiana per la Ricerca sul Cancro (AIRC)

Project ID: IG 21567

Targeting allo-reactive Natural Killer cell immune reconstitution in hematologic tumors after bone marrow transplant

collaborations

Humanitas Cancer Center
IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy

Department of Experimental Medicine (DIMES)
University of Genoa, Genoa, Italy

Division of Hematology, Department of Oncology
A.O.U. Città della Salute e della Scienza di Torino, Torino, Italy

Institute for Virology
University Hospital Essen, University Duisburg-Essen, Essen, Germany

Unit of Hematology and Cellular Therapy
IRCCS Ospedale Policlinico San Martino, Genoa, Italy

related publications

Persistence of KIRneg NK cells after haploidentical hematopoietic stem cell transplantation protects from human cytomegalovirus infection/reactivation
Di Vito C, Coianiz N, Calvi M, Terzoli S, Zaghi E, Puccio S, Frigo A, Mariotti J, De Philippis C, Mannina D, Sarina B, Mineri R, Le-Trilling VTK, Trilling M, Castagna L, Bramanti S, Santoro A and Mavilio D.
Front. Immunol. 2024 Jan;14:1266051. doi: 10.3389/fimmu.2023.1266051.
Extracellular Vesicles as Biomarkers of Acute Graft-vs.-Host Disease After Haploidentical Stem Cell Transplantation and Post-Transplant Cyclophosphamide
Lia G, Di Vito C, Bruno S, Tapparo M, Brunello L, Santoro A, Mariotti J, Bramanti S, Zaghi E, Calvi M, Comba L, Fascì M, Giaccone L, Camussi G, Boyle EM, Castagna L, Evangelista A, Mavilio D, Bruno B.
Front Immunol. 2022 Jan 25;12:816231. doi: 10.3389/fimmu.2021.816231.

Single-cell profiling identifies impaired adaptive NK cells expanded after HCMV reactivation in haploidentical HSCT
Zaghi E, Calvi M, Puccio S, Spata G, Terzoli S, Peano C, Roberto A, De Paoli F, van Beek JJ, Mariotti J, De Philippis C, Sarina B, Mineri R, Bramanti S, Santoro A, Le-Trilling VTK, Trilling M, Marcenaro E, Castagna L, Di Vito C, Lugli E, Mavilio D.
JCI Insight. 2021 Jun 22;6(12):e146973. doi: 10.1172/jci.insight.146973.
Extracellular Vesicles After Allogeneic Hematopoietic Cell Transplantation: Emerging Role in Post-Transplant Complications
Lia G, Di Vito C, Cerrano M, Brunello L, Calcaterra F, Tapparo M, Giaccone L, Mavilio D, Bruno B.
Front Immunol. 2020 Mar 20;11:422. doi: 10.3389/fimmu.2020.00422.

Innate Immune Responses in the Outcome of Haploidentical Hematopoietic Stem Cell Transplantation to Cure Hematologic Malignancies
Zaghi E, Calvi M, Di Vito C, Mavilio D.
Front Immunol. 2019 Nov 28;10:2794. doi: 10.3389/fimmu.2019.02794.
Targeting NKG2A to elucidate natural killer cell ontogenesis and to develop novel immune-therapeutic strategies in cancer therapy

Zaghi E, Calvi M, Marcenaro E, Mavilio D, Di Vito C.
J Leukoc Biol. 2019 Jun;105(6):1243-1251. doi: 10.1002/JLB.MR0718-300R.

The early expansion of anergic NKG2Apos/CD56dim/CD16neg natural killer represents a therapeutic target in haploidentical hematopoietic stem cell transplantation
Roberto A, Di Vito C, Zaghi E, Mazza EMC, Capucetti A, Calvi M, Tentorio P, Zanon V, Sarina B, Mariotti J, Bramanti S, Tenedini E, Tagliafico E, Bicciato S, Santoro A, Roederer M, Marcenaro E, Castagna L, Lugli E, Mavilio D.
Haematologica. 2018 Aug;103(8):1390-1402. doi: 10.3324/haematol.2017.186619.
Role of naive-derived T memory stem cells in T-cell reconstitution following allogeneic transplantation
Roberto A, Castagna L, Zanon V, Bramanti S, Crocchiolo R, McLaren JE, Gandolfi S, Tentorio P, Sarina B, Timofeeva I, Santoro A, Carlo-Stella C, Bruno B, Carniti C, Corradini P, Gostick E, Ladell K, Price DA, Roederer M, Mavilio D, Lugli E.
Blood. 2015 Apr 30;125(18):2855-64. doi: 10.1182/blood-2014-11-608406.
B-cell reconstitution recapitulates B-cell lymphopoiesis following haploidentical BM transplantation and post-transplant CY
Roberto A, Castagna L, Gandolfi S, Zanon V, Bramanti S, Sarina B, Crocchiolo R, Todisco E, Carlo-Stella C, Tentorio P, Timofeeva I, Santoro A, Della Bella S, Roederer M, Mavilio D, Lugli E.
Bone Marrow Transplant. 2015 Feb;50(2):317-9. doi: 10.1038/bmt.2014.266.