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Adapter Chimeric Antigen Receptor (AdCAR)-Engineered NK-92 Cells for the Multiplex Targeting of Bone Metastases
Stefan Grote1, Frank Traub2, Joerg Mittelstaet3
1Department of Hematology and Oncology, University Hospital Tuebingen, Children's Hospital, 72076 Tuebingen, Germany.
Background:
Since metastatic spreading of solid tumor cells often leads to a fatal outcome for most cancer patients, new approaches for patient-individualized, targeted immunotherapy are urgently needed.
Methods:
Here, we established cell lines from four bone metastases of different tumor entities. We assessed AdCAR NK-92-mediated cytotoxicity in vitro in standard cytotoxicity assays as well as 3D spheroid models Results: AdCAR-engineered NK-92 cells successfully demonstrated distinct and specific cytotoxic potential targeting different tumor antigens expressed on cell lines established from bone metastases of mammary, renal cell and colorectal carcinoma as well as melanomas. In that process AdCAR NK-92 cells produced a multitude of NK effector molecules as well as pro inflammatory cytokines. Furthermore, AdCAR NK-92 showed increased cytotoxicity in 3D spheroid models which can recapitulate in vivo architecture, thereby bridging the gap between in vitro and in vivo models.
Conclusions:
AdCAR NK-92 cells may provide an interesting and promising "off-the-shelf" cellular product for the targeted therapy of cancers metastasizing to the bone, while utilization of clinically approved, therapeutic antibodies, as exchangeable adapter molecules can facilitate quick clinical translation.
Insights
Engineered NK-92 cells show promise for targeted immunotherapy against bone metastases. These AdCAR NK-92 cells effectively target various cancer antigens, offering a potential "off-the-shelf" treatment.
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.
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