Abstract:
: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.
journal_name
Oncoimmunologyjournal_title
Oncoimmunologyauthors
Bazett M,Costa AM,Bosiljcic M,Anderson RM,Alexander MP,Wong SWY,Dhanji S,Chen JM,Pankovich J,Lam S,Sutcliffe S,Gunn H,Kalyan S,Mullins DWdoi
10.1080/2162402X.2017.1398875subject
Has Abstractpub_date
2017-11-27 00:00:00pages
e1398875issue
3eissn
2162-4011issn
2162-402Xpii
1398875journal_volume
7pub_type
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