Harnessing innate lung anti-cancer effector functions with a novel bacterial-derived immunotherapy
Acute infection is known to induce strong anti-tumor immune responses, but clinical translation has been hindered by the lack of an effective strategy to safely and consistently provoke a therapeutic response. These limitations are overcome with a novel treatment approach involving repeated subcutan...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2018-03-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2017.1398875 |
| _version_ | 1818267412881997824 |
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| author | Mark Bazett Amanda M. Costa Momir Bosiljcic Rebecca M. Anderson Matthew P. Alexander Stephanie W. Y. Wong Salim Dhanji Jenny MH Chen Jim Pankovich Stephen Lam Simon Sutcliffe Hal Gunn Shirin Kalyan David W. Mullins |
| author_facet | Mark Bazett Amanda M. Costa Momir Bosiljcic Rebecca M. Anderson Matthew P. Alexander Stephanie W. Y. Wong Salim Dhanji Jenny MH Chen Jim Pankovich Stephen Lam Simon Sutcliffe Hal Gunn Shirin Kalyan David W. Mullins |
| author_sort | Mark Bazett |
| collection | DOAJ |
| description | Acute infection is known to induce strong anti-tumor immune responses, but clinical translation has been hindered by the lack of an effective strategy to safely and consistently provoke a therapeutic response. These limitations are overcome with a novel treatment approach involving repeated subcutaneous delivery of a Klebsiella-derived investigational immunotherapeutic, QBKPN. In preclinical models of lung cancer, QBKPN administration consistently showed anti-cancer efficacy, which was dependent on Klebsiella pre-exposure, but was independent of adaptive immunity. Rather, QBKPN induced anti-tumor innate immunity that required NK cells and NKG2D engagement. QBKPN increased NK cells and macrophages in the lungs, altered macrophage polarization, and augmented the production of cytotoxic molecules. An exploratory trial in patients with non-small cell lung cancer demonstrated QBKPN was well tolerated, safe, and induced peripheral immune changes suggestive of macrophage polarization and reduction of PD-1 and PD-L1 expression on leukocytes. These data demonstrate preclinical efficacy, and clinical safety and tolerability, for this cancer immunotherapy strategy that exploits innate anti-tumor immune mechanisms. |
| first_indexed | 2024-12-12T20:22:12Z |
| format | Article |
| id | doaj.art-edc987a804c9426cbb1774284128f680 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-12T20:22:12Z |
| publishDate | 2018-03-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-edc987a804c9426cbb1774284128f6802022-12-22T00:13:14ZengTaylor & Francis GroupOncoImmunology2162-402X2018-03-017310.1080/2162402X.2017.13988751398875Harnessing innate lung anti-cancer effector functions with a novel bacterial-derived immunotherapyMark Bazett0Amanda M. Costa1Momir Bosiljcic2Rebecca M. Anderson3Matthew P. Alexander4Stephanie W. Y. Wong5Salim Dhanji6Jenny MH Chen7Jim Pankovich8Stephen Lam9Simon Sutcliffe10Hal Gunn11Shirin Kalyan12David W. Mullins13Qu Biologics Inc.Department of Microbiology and Immunology, Geisel School of Medicine at DartmouthQu Biologics Inc.Qu Biologics Inc.Department of Microbiology and Immunology, Geisel School of Medicine at DartmouthQu Biologics Inc.Qu Biologics Inc.Qu Biologics Inc.Qu Biologics Inc.BC Cancer Research CenterQu Biologics Inc.Qu Biologics Inc.Qu Biologics Inc.Department of Microbiology and Immunology, Geisel School of Medicine at DartmouthAcute infection is known to induce strong anti-tumor immune responses, but clinical translation has been hindered by the lack of an effective strategy to safely and consistently provoke a therapeutic response. These limitations are overcome with a novel treatment approach involving repeated subcutaneous delivery of a Klebsiella-derived investigational immunotherapeutic, QBKPN. In preclinical models of lung cancer, QBKPN administration consistently showed anti-cancer efficacy, which was dependent on Klebsiella pre-exposure, but was independent of adaptive immunity. Rather, QBKPN induced anti-tumor innate immunity that required NK cells and NKG2D engagement. QBKPN increased NK cells and macrophages in the lungs, altered macrophage polarization, and augmented the production of cytotoxic molecules. An exploratory trial in patients with non-small cell lung cancer demonstrated QBKPN was well tolerated, safe, and induced peripheral immune changes suggestive of macrophage polarization and reduction of PD-1 and PD-L1 expression on leukocytes. These data demonstrate preclinical efficacy, and clinical safety and tolerability, for this cancer immunotherapy strategy that exploits innate anti-tumor immune mechanisms.http://dx.doi.org/10.1080/2162402X.2017.1398875immunotherapyinnate immunityklebsiellalung cancernk cellsnkg2dnsclc |
| spellingShingle | Mark Bazett Amanda M. Costa Momir Bosiljcic Rebecca M. Anderson Matthew P. Alexander Stephanie W. Y. Wong Salim Dhanji Jenny MH Chen Jim Pankovich Stephen Lam Simon Sutcliffe Hal Gunn Shirin Kalyan David W. Mullins Harnessing innate lung anti-cancer effector functions with a novel bacterial-derived immunotherapy OncoImmunology immunotherapy innate immunity klebsiella lung cancer nk cells nkg2d nsclc |
| title | Harnessing innate lung anti-cancer effector functions with a novel bacterial-derived immunotherapy |
| title_full | Harnessing innate lung anti-cancer effector functions with a novel bacterial-derived immunotherapy |
| title_fullStr | Harnessing innate lung anti-cancer effector functions with a novel bacterial-derived immunotherapy |
| title_full_unstemmed | Harnessing innate lung anti-cancer effector functions with a novel bacterial-derived immunotherapy |
| title_short | Harnessing innate lung anti-cancer effector functions with a novel bacterial-derived immunotherapy |
| title_sort | harnessing innate lung anti cancer effector functions with a novel bacterial derived immunotherapy |
| topic | immunotherapy innate immunity klebsiella lung cancer nk cells nkg2d nsclc |
| url | http://dx.doi.org/10.1080/2162402X.2017.1398875 |
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