Combining NK cells and mAb9.2.27 to combat NG2-dependent and anti-inflammatory signals in glioblastoma

Justyna Kmiecik; Andrea Gras Navarro; Aurelie Poli; Jesús Planagumà Planagumà; Jacques Zimmer; Martha Chekenya

doi:10.4161/onci.27185

Combining NK cells and mAb9.2.27 to combat NG2-dependent and anti-inflammatory signals in glioblastoma

Oncoimmunology. 2014 Jan 1;3(1):e27185. doi: 10.4161/onci.27185.

Authors

Justyna Kmiecik¹, Andrea Gras Navarro¹, Aurelie Poli², Jesús Planagumà Planagumà³, Jacques Zimmer², Martha Chekenya⁴

Affiliations

¹ University of Bergen; Institute for Biomedicine; Bergen, Norway.
² Laboratoire d'Immunogénétique-Allergologie; CRP-Santé, Luxembourg.
³ Department of Neuroimmunology; Hospital Clinic (IDIBAPS); Barcelona, Spain.
⁴ University of Bergen; Institute for Biomedicine; Bergen, Norway ; University of Bergen, Institute for Clinical Dentistry; Bergen, Norway.

Abstract

Glioblastoma is a deadly brain cancer with limited treatment options. Targeting chondroitin sulfate proteoglycan 4 (CSPG4, best known as NG2) with the monoclonal antibody mAb9.2.27 and activated natural killer (NK) cells abrogated the tumor growth and prolonged the survival of glioblastoma-bearing animals by favoring the establishment of a pro-inflammatory microenvironment. The combination of NK cells and mAb9.2.27 recruited ED1⁺CCR2^low macrophages that stimulated ED1⁺ED2^lowMHCII^high microglial cells to exert robust cytotoxicity. Our findings demonstrate the therapeutic potential of targeting salient tumor associated-antigens.

Keywords: CNS immunosurveillance; CSPG4; NK cells; glioblastoma; passive immunotherapy.

Publication types

Research Support, Non-U.S. Gov't