Adapter Chimeric Antigen Receptor (AdCAR)-Engineered NK-92 Cells for the Multiplex Targeting of Bone Metastases

Area of Science:

• Immunology
• Oncology
• Cell Therapy

Background:

• Metastatic spreading of solid tumors is a primary cause of cancer mortality.
• There is a critical need for personalized and targeted immunotherapies for cancer patients.

Purpose of the Study:

• To develop and evaluate AdCAR NK-92 cells for targeted immunotherapy against bone metastases.
• To assess the efficacy of AdCAR NK-92 cells in vitro and in 3D spheroid models.

Main Methods:

• Established cell lines from four bone metastases of different tumor types.
• Assessed AdCAR NK-92 cell-mediated cytotoxicity using standard assays and 3D spheroid models.
• Analyzed the production of NK effector molecules and pro-inflammatory cytokines.

Main Results:

• AdCAR NK-92 cells demonstrated specific cytotoxicity against tumor antigens from mammary, renal cell, colorectal carcinomas, and melanomas.
• Engineered NK-92 cells produced significant levels of NK effector molecules and pro-inflammatory cytokines.
• Enhanced cytotoxicity was observed in 3D spheroid models, which better mimic in vivo tumor architecture.

Conclusions:

• AdCAR NK-92 cells represent a promising "off-the-shelf" cellular therapy for bone metastasis.
• The use of exchangeable adapter molecules with clinically approved antibodies can expedite clinical translation.