Cryopreservation of Natural Killer Cells Pre-Complexed with Innate Cell Engagers
Innate cell engager (ICE<sup>®</sup>) constructs are bispecific tetravalent antibodies targeting specific tumor antigens and simultaneously engaging natural killer (NK) cell and macrophage receptors for the destruction of tumor cells. Pre-complexing of ICE<sup>®</sup> constru...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Antibodies |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4468/11/1/12 |
| _version_ | 1797473235098402816 |
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| author | Uwe Reusch Kristina Ellwanger Ivica Fucek Thomas Müller Ute Schniegler-Mattox Joachim Koch Michael Tesar |
| author_facet | Uwe Reusch Kristina Ellwanger Ivica Fucek Thomas Müller Ute Schniegler-Mattox Joachim Koch Michael Tesar |
| author_sort | Uwe Reusch |
| collection | DOAJ |
| description | Innate cell engager (ICE<sup>®</sup>) constructs are bispecific tetravalent antibodies targeting specific tumor antigens and simultaneously engaging natural killer (NK) cell and macrophage receptors for the destruction of tumor cells. Pre-complexing of ICE<sup>®</sup> constructs with adoptive NK cells is a novel approach to enhance NK cell activity. The suitability of such complexes for cryopreservation, whilst retaining the biological activity and specificity, may enable the development of off-the-shelf NK cell products. This study investigates the binding affinity of ICE<sup>®</sup> constructs targeting EpCAM and NK cell receptors CD16A, NKG2D, or NKp46 to the corresponding antigens, the ICE<sup>®</sup> antitumor activity, and feasibility of cryopreservation. Cell surface retention assays using primary NK cells confirmed a substantially slower ICE<sup>®</sup> construct dissociation kinetics compared with control molecules, suggesting the formation of durable complexes independently of the CD16A polymorphism. The high-affinity NK cell and EpCAM/CD16A ICE<sup>®</sup> complexes were superior to those engaging NKG2D or NKp46 receptors when tested for the NK-cell-mediated elimination of EpCAM-expressing tumor cells. Moreover, the potency and efficacy of these complexes were unaffected after a single freeze–thaw cycle. CD16A-selective ICE<sup>®</sup> drug candidates complexed with NK cells hold promise as novel cryopreserved off-the-shelf NK cell products with chimeric antigen receptor-like NK cell properties, capable of effective depletion of tumor cells. |
| first_indexed | 2024-03-09T20:12:00Z |
| format | Article |
| id | doaj.art-c2ab650ca3c04175a6acf0e1b84c5100 |
| institution | Directory Open Access Journal |
| issn | 2073-4468 |
| language | English |
| last_indexed | 2024-03-09T20:12:00Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibodies |
| spelling | doaj.art-c2ab650ca3c04175a6acf0e1b84c51002023-11-24T00:12:29ZengMDPI AGAntibodies2073-44682022-02-011111210.3390/antib11010012Cryopreservation of Natural Killer Cells Pre-Complexed with Innate Cell EngagersUwe Reusch0Kristina Ellwanger1Ivica Fucek2Thomas Müller3Ute Schniegler-Mattox4Joachim Koch5Michael Tesar6Affimed GmbH, 69120 Heidelberg, GermanyAffimed GmbH, 69120 Heidelberg, GermanyAffimed GmbH, 69120 Heidelberg, GermanyAffimed GmbH, 69120 Heidelberg, GermanyAffimed GmbH, 69120 Heidelberg, GermanyAffimed GmbH, 69120 Heidelberg, GermanyAffimed GmbH, 69120 Heidelberg, GermanyInnate cell engager (ICE<sup>®</sup>) constructs are bispecific tetravalent antibodies targeting specific tumor antigens and simultaneously engaging natural killer (NK) cell and macrophage receptors for the destruction of tumor cells. Pre-complexing of ICE<sup>®</sup> constructs with adoptive NK cells is a novel approach to enhance NK cell activity. The suitability of such complexes for cryopreservation, whilst retaining the biological activity and specificity, may enable the development of off-the-shelf NK cell products. This study investigates the binding affinity of ICE<sup>®</sup> constructs targeting EpCAM and NK cell receptors CD16A, NKG2D, or NKp46 to the corresponding antigens, the ICE<sup>®</sup> antitumor activity, and feasibility of cryopreservation. Cell surface retention assays using primary NK cells confirmed a substantially slower ICE<sup>®</sup> construct dissociation kinetics compared with control molecules, suggesting the formation of durable complexes independently of the CD16A polymorphism. The high-affinity NK cell and EpCAM/CD16A ICE<sup>®</sup> complexes were superior to those engaging NKG2D or NKp46 receptors when tested for the NK-cell-mediated elimination of EpCAM-expressing tumor cells. Moreover, the potency and efficacy of these complexes were unaffected after a single freeze–thaw cycle. CD16A-selective ICE<sup>®</sup> drug candidates complexed with NK cells hold promise as novel cryopreserved off-the-shelf NK cell products with chimeric antigen receptor-like NK cell properties, capable of effective depletion of tumor cells.https://www.mdpi.com/2073-4468/11/1/12adoptive transferbispecific antibodycryopreservationinnate cell engagerinnate immune cellsnatural killer cell |
| spellingShingle | Uwe Reusch Kristina Ellwanger Ivica Fucek Thomas Müller Ute Schniegler-Mattox Joachim Koch Michael Tesar Cryopreservation of Natural Killer Cells Pre-Complexed with Innate Cell Engagers Antibodies adoptive transfer bispecific antibody cryopreservation innate cell engager innate immune cells natural killer cell |
| title | Cryopreservation of Natural Killer Cells Pre-Complexed with Innate Cell Engagers |
| title_full | Cryopreservation of Natural Killer Cells Pre-Complexed with Innate Cell Engagers |
| title_fullStr | Cryopreservation of Natural Killer Cells Pre-Complexed with Innate Cell Engagers |
| title_full_unstemmed | Cryopreservation of Natural Killer Cells Pre-Complexed with Innate Cell Engagers |
| title_short | Cryopreservation of Natural Killer Cells Pre-Complexed with Innate Cell Engagers |
| title_sort | cryopreservation of natural killer cells pre complexed with innate cell engagers |
| topic | adoptive transfer bispecific antibody cryopreservation innate cell engager innate immune cells natural killer cell |
| url | https://www.mdpi.com/2073-4468/11/1/12 |
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