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Adapter Chimeric Antigen Receptor (AdCAR)-Engineered NK-92 Cells for the Multiplex Targeting of Bone Metastases
SIMPLE SUMMARY: Metastatic disease remains one of the biggest challenges for tumor therapy. The aim of our study was the preclinical evaluation of adapter chimeric antigen receptor (AdCAR)-engineered NK-92 cell efficacy as a possible treatment strategy for various types of bone metastatic cancers. W...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961358/ https://www.ncbi.nlm.nih.gov/pubmed/33807875 http://dx.doi.org/10.3390/cancers13051124 |
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author | Grote, Stefan Traub, Frank Mittelstaet, Joerg Seitz, Christian Kaiser, Andrew Handgretinger, Rupert Schleicher, Sabine |
author_facet | Grote, Stefan Traub, Frank Mittelstaet, Joerg Seitz, Christian Kaiser, Andrew Handgretinger, Rupert Schleicher, Sabine |
author_sort | Grote, Stefan |
collection | PubMed |
description | SIMPLE SUMMARY: Metastatic disease remains one of the biggest challenges for tumor therapy. The aim of our study was the preclinical evaluation of adapter chimeric antigen receptor (AdCAR)-engineered NK-92 cell efficacy as a possible treatment strategy for various types of bone metastatic cancers. We confirmed that AdCAR NK-92 cells successfully induces tumor cell lysis in bone metastasis cell lines derived from mammary, renal cell and colorectal carcinoma as well as melanoma in a specific and controllable manner, thus, establishing a potent cellular product with universal applicability and quick clinical translation potential for the treatment of solid tumors, including metastases. ABSTRACT: 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. |
format | Online Article Text |
id | pubmed-7961358 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-79613582021-03-17 Adapter Chimeric Antigen Receptor (AdCAR)-Engineered NK-92 Cells for the Multiplex Targeting of Bone Metastases Grote, Stefan Traub, Frank Mittelstaet, Joerg Seitz, Christian Kaiser, Andrew Handgretinger, Rupert Schleicher, Sabine Cancers (Basel) Article SIMPLE SUMMARY: Metastatic disease remains one of the biggest challenges for tumor therapy. The aim of our study was the preclinical evaluation of adapter chimeric antigen receptor (AdCAR)-engineered NK-92 cell efficacy as a possible treatment strategy for various types of bone metastatic cancers. We confirmed that AdCAR NK-92 cells successfully induces tumor cell lysis in bone metastasis cell lines derived from mammary, renal cell and colorectal carcinoma as well as melanoma in a specific and controllable manner, thus, establishing a potent cellular product with universal applicability and quick clinical translation potential for the treatment of solid tumors, including metastases. ABSTRACT: 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. MDPI 2021-03-05 /pmc/articles/PMC7961358/ /pubmed/33807875 http://dx.doi.org/10.3390/cancers13051124 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Grote, Stefan Traub, Frank Mittelstaet, Joerg Seitz, Christian Kaiser, Andrew Handgretinger, Rupert Schleicher, Sabine Adapter Chimeric Antigen Receptor (AdCAR)-Engineered NK-92 Cells for the Multiplex Targeting of Bone Metastases |
title | Adapter Chimeric Antigen Receptor (AdCAR)-Engineered NK-92 Cells for the Multiplex Targeting of Bone Metastases |
title_full | Adapter Chimeric Antigen Receptor (AdCAR)-Engineered NK-92 Cells for the Multiplex Targeting of Bone Metastases |
title_fullStr | Adapter Chimeric Antigen Receptor (AdCAR)-Engineered NK-92 Cells for the Multiplex Targeting of Bone Metastases |
title_full_unstemmed | Adapter Chimeric Antigen Receptor (AdCAR)-Engineered NK-92 Cells for the Multiplex Targeting of Bone Metastases |
title_short | Adapter Chimeric Antigen Receptor (AdCAR)-Engineered NK-92 Cells for the Multiplex Targeting of Bone Metastases |
title_sort | adapter chimeric antigen receptor (adcar)-engineered nk-92 cells for the multiplex targeting of bone metastases |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961358/ https://www.ncbi.nlm.nih.gov/pubmed/33807875 http://dx.doi.org/10.3390/cancers13051124 |
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