NYMC Faculty Publications

Combinatorial Immunotherapy of Anti-MCAM CAR-Modified Expanded Natural Killer Cells and NKTR-255 Against Neuroblastoma

Author Type(s)

Faculty

DOI

10.1016/j.omton.2024.200894

Journal Title

Molecular Therapy Oncology

Document Type

Article

Publication Date

12-19-2024

Department

Pediatrics

Keywords

chimeric antigen receptor, MCAM, MT: Regular Issue, natural killer cell, neuroblastoma, NKTR-255

Disciplines

Medicine and Health Sciences

Abstract

Pediatric patients with recurrent metastatic neuroblastoma (NB) have a dismal 5-year survival. Novel therapeutic approaches are urgently needed. The melanoma cell adhesion molecule (MCAM/CD146/MUC18) is expressed in a variety of pediatric solid tumors, including NB, and constitutes a novel target for immunotherapy. Here, we developed a chimeric antigen receptor (CAR) expressing natural killer (NK) cell-targeting MCAM by non-viral electroporation of CAR mRNA into ex vivo expanded NK cells. Expression of anti-MCAM CAR significantly enhanced NK cell cytotoxic activity compared to mock NK cells against MCAMhigh but not MCAMlow/knockout NB cells in vitro. Anti-MCAM-CAR-NK cell treatment significantly decreased tumor growth and prolonged animal survival in an NB xenograft mouse model. NKTR-255, a polymer-conjugated recombinant human interleukin-15 agonist, significantly stimulated NK cell proliferation and expansion and further enhanced the in vitro cytotoxic activity and in vivo anti-tumor efficacy of anti-MCAM-CAR-NK cells against NB. Our preclinical studies demonstrate that ex vivo expanded and modified anti-MCAM-CAR-NK cells alone and/or in combination with NKTR-255 are promising novel alternative therapeutic approaches to targeting MCAMhigh malignant NB.

Link to Full Text

Share

COinS