Efficient and Robust NK-Cell Transduction With Baboon Envelope Pseudotyped Lentivector

Colamartino, A.B.L. ; Lemieux, W. ; Bifsha, P. ; Nicoletti, S. ; Chakravarti, N. ; Sanz, J. (Universidad de Zaragoza) ; Roméro, H. ; Selleri, S. ; Béland, K. ; Guiot, M. ; Tremblay-Laganière, C. ; Dicaire, R. ; Barreiro, L. ; Lee, D.A. ; Verhoeyen, E. ; Haddad, E.

Resumen: NK-cell resistance to transduction is a major technical hurdle for developing NK-cell immunotherapy. By using Baboon envelope pseudotyped lentiviral vectors (BaEV-LVs) encoding eGFP, we obtained a transduction rate of 23.0 ± 6.6% (mean ± SD) in freshly-isolated human NK-cells (FI-NK) and 83.4 ± 10.1% (mean ± SD) in NK-cells obtained from the NK-cell Activation and Expansion System (NKAES), with a sustained transgene expression for at least 21 days. BaEV-LVs outperformed Vesicular Stomatitis Virus type-G (VSV-G)-, RD114- and Measles Virus (MV)- pseudotyped LVs (p < 0.0001). mRNA expression of both BaEV receptors, ASCT1 and ASCT2, was detected in FI-NK and NKAES, with higher expression in NKAES. Transduction with BaEV-LVs encoding for CAR-CD22 resulted in robust CAR-expression on 38.3 ± 23.8% (mean ± SD) of NKAES cells, leading to specific killing of NK-resistant pre-B-ALL-RS4;11 cell line. Using a larger vector encoding a dual CD19/CD22-CAR, we were able to transduce and re-expand dual-CAR-expressing NKAES, even with lower viral titer. These dual-CAR-NK efficiently killed both CD19KO- and CD22KO-RS4;11 cells. Our results suggest that BaEV-LVs may efficiently enable NK-cell biological studies and translation of NK-cell-based immunotherapy to the clinic.

Idioma: Inglés

DOI: 10.3389/fimmu.2019.02873

Año: 2019

Publicado en: Frontiers in Immunology 10 (2019), 2873 1-7
ISSN: 1664-3224

Factor impacto JCR: 5.085 (2019)

Categ. JCR: IMMUNOLOGY rank: 38 / 158 = 0.241 (2019) - Q1 - T1

Factor impacto SCIMAGO: 2.116 - Immunology and Allergy (Q1) - Immunology (Q1)

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Física Teórica (Dpto. Física Teórica)