Rondahl, Veronica
- Institutionen för husdjurens biovetenskaper, Sveriges lantbruksuniversitet
Sammanfattning
CD19 CAR-T cell therapy shows striking results in treating B cell malignancies. However, approximately two-thirds of the lymphoma patients eventually relapse, with about one-third displaying CD19-negative tumors at relapse. Our previous study showed that CAR-T cells armed with the Helicobacterpylori neutrophil-activating protein (NAP), CAR(NAP)-T cells, can trigger a bystander immune response and eliminate CAR-target-antigen-negative tumor cells. Here, we report the development of CD20-targeted CAR-T cells (CAR20-T cells), with the targeting moiety from rituximab, and the safety and efficacy of NAP-armed CAR-T cells. CAR20-T cells displayed efficient and specific cytotoxic potential against multiple human B cell lymphoma cell lines in vitro. In addition, primary mantle cell lymphoma cells, isolated from a patient who relapsed after rituximab treatment, can also be eliminated by CAR20-T cells. CAR20(NAP)-T cells delayed tumor growth and prolonged survival of mice with lymphoma. No obvious histopathological alteration in major organs were observed in mice treated with CAR(NAP)-T cells. Further, no excessive cytokine release or immune cell activation was observed when human blood from healthy volunteers was exposed to recombinant NAP protein in an ex vivo blood loop assay, suggesting a safe therapeutic profile for NAP. Taken together, these results warrant the clinical investigation of CAR20(NAP)-T cells.
Nyckelord
CD20; Chimeric antigen receptor; CAR-T cell; Neutrophil-activating protein; Safety; Toxicity; Lymphoma; Cytokine release; Rituximab
Publicerad i
Cancer Immunology, Immunotherapy
2025, volym: 74, nummer: 8, artikelnummer: 262
Utgivare: SPRINGER
SLU författare
UKÄ forskningsämne
Cell- och molekylärbiologi
Cancer och onkologi
Publikationens identifierare
- DOI: https://doi.org/10.1007/s00262-025-04112-1
Permanent länk till denna sida (URI)
https://res.slu.se/id/publ/143112