Donor-derived CARCIK-CD19 cells engineered with Sleeping Beauty transposon in acute lymphoblastic leukemia relapsed after allogeneic transplantation
Non-viral engineering can ease CAR-T cell production and reduce regulatory and cost requirements. We utilized Sleeping Beauty transposon to engineer donor-derived anti-CD19.CD28.OX40.CD3zeta T cells differentiated in cytokine-induced killer (CARCIK-CD19) for B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients relapsed after allogeneic hematopoietic stem cell transplantation (alloHSCT). We report the results of CARCIK-CD19 observed in 36 patients (4 children and 32 adults) treated according to the final recommended dose. Cytokine release syndrome of grade 2 or lower occurred in 15 patients, ICANS grade 2 in 1 patient, and late-onset peripheral neurotoxicity of grade 3 in 2 patients. GVHD never occurred after treatment with allogeneic CARCIK-CD19. Complete remission was achieved by 30 out of 36 patients (83.3%), with MRD negativity in 89% of responders. With a median follow-up of 2.2 years, the 1-year overall survival was 57.0%, and event-free survival was 32.0%. The median duration of response at 1 year was 38.6%. CAR-T cells expanded rapidly after infusion and remained detectable for over 2 years. Integration site analysis after infusion showed a high clonal diversity. These data demonstrated that SB-engineered CAR-T cells are safe and induce durable remission in heavily pretreated patients with BCP-ALL relapsed after alloHSCT. Trial registration: The phase 1/2 and phase II trials are registered at www.clinicaltrials.gov as NCT#03389035 and NCT#05252403.
Authors
- Giuliana Rizzuto (ORCID: https://orcid.org/0000-0001-7518-2521)
- Sara Napolitano (ORCID: https://orcid.org/0000-0003-2145-7395)
- Elisa Gotti
- Giuseppe Gritti (ORCID: https://orcid.org/0000-0002-6789-5123)
- Silvia Ferrari (ORCID: https://orcid.org/0000-0002-9917-2843)
- Fabrizio Benedicenti (ORCID: https://orcid.org/0000-0002-6378-125X)
- Josée Golay (ORCID: https://orcid.org/0000-0002-7932-909X)
- Chiara Capelli (ORCID: https://orcid.org/0000-0002-4454-1541)
- Sarah Tettamanti (ORCID: https://orcid.org/0000-0002-7327-418X)
- Giulio Spinozzi (ORCID: https://orcid.org/0000-0002-4220-2474)
- Martino Introna (ORCID: https://orcid.org/0000-0001-6216-0892)
- Stefania Galimberti (ORCID: https://orcid.org/0000-0003-1504-7242)
- Cristian Meli
- Chiara F. Magnani (ORCID: https://orcid.org/0000-0003-2474-2159)
- Giuseppe Dastoli
- Andrea Biondi (ORCID: https://orcid.org/0000-0002-6757-6173)
- Federico Lussana (ORCID: https://orcid.org/0000-0002-6510-8616)
- Giulia Risca (ORCID: https://orcid.org/0000-0002-6389-9434)
- Alessandro Rambaldi (ORCID: https://orcid.org/0000-0002-3739-7502)
- Muriel Paganessi
- Alex Moretti (ORCID: https://orcid.org/0000-0003-3596-825X)
- Giulia Pais (ORCID: https://orcid.org/0009-0005-5621-4803)
- Chiara Buracchi (ORCID: https://orcid.org/0000-0002-5345-7448)
- Eugenio Montini (ORCID: https://orcid.org/0000-0003-1771-6067)
- Anna Grassi (ORCID: https://orcid.org/0000-0001-7273-4263)
- Benedetta Cabiati
- Giovanni Cazzaniga (ORCID: https://orcid.org/0000-0003-2955-4528)
- Adriana Balduzzi (ORCID: https://orcid.org/0000-0002-5879-0610)
- Benedetta Rambaldi (ORCID: https://orcid.org/0000-0002-5246-9471)
- Maria Grazia Valsecchi (ORCID: https://orcid.org/0000-0001-5574-3504)
- Giuseppe Gaipa (ORCID: https://orcid.org/0000-0002-1006-5946)
- Daniela Belotti
- Gian Maria Borleri
Institutions
- University of Milan (IT)
- University of Zurich (CH)
- University Hospital of Zurich (CH)
- Ospedale Papa Giovanni XXIII (IT)
- Azienda Ospedaliera San Gerardo (IT)
- The San Raffaele Telethon Institute for Gene Therapy (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT)
- University of Milano-Bicocca (IT)
Publication Details
- Journal
- Blood Cancer Journal
- Published
- 2025-04-03
- DOI
- https://doi.org/10.1038/s41408-025-01260-6
- Citations
- 9
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 9.41
Funders
- Cancer Research UK
- Fundación Científica Asociación Española Contra el Cáncer
- Ministero della Salute
- Associazione Italiana per la Ricerca sul Cancro
- Regione Lombardia
- Ministero dell'Università e della Ricerca
- Fondazione Regionale per la Ricerca Biomedica
- Alleanza Contro il Cancro
- Agenzia Italiana del Farmaco, Ministero della Salute