Tumor lysis with LTX-401 creates anticancer immunity. (3rd July 2019)

• Record Type: Journal Article
• Authors: Xie, Wei; Mondragón, Laura; Mauseth, Brynjar; Wang, Yan; Pol, Jonathan; Lévesque, Sarah; Zhou, Heng; Yamazaki, Takahiro; Eksteen, Johannes J.; Zitvogel, Laurence; Sveinbjørnsson, Baldur; Rekdal, Øystein; Kepp, Oliver; Kroemer, Guido
• Is Part Of: Oncoimmunology. Volume 8:Number 7(2019)
• Publication Date: 2019-07-03
• Subjects: Oncolysis -- anticancer therapy -- immunogenic cell death -- checkpoint blockade; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2019.1594555
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: Local immunotherapies such as the intratumoral injection of oncolytic compounds aim at reinstating and enhancing systemic anticancer immune responses. LTX-315 is a first-in-class, clinically evaluated oncolytic peptide-based local immunotherapy that meets these criteria. Here, we show that LTX-401, yet another oncolytic compound designed for local immunotherapy, depicts a similar safety profile and that sequential local inoculation of LTX-401 was able to cure immunocompetent host from subcutaneous MCA205 and TC-1 cancers. Cured animals exhibited long-term immune memory effects that rendered them resistant to rechallenge with syngeneic tumors. Nevertheless, the local treatment with LTX-401 alone had only limited abscopal effects on secondary contralateral lesions. Anticancer effects resulting from single as well as sequential injections of LTX-401 were boosted in combination with PD-1 and CTLA-4 immune checkpoint blockade (ICB), and sequential LTX-401 treatment combined with double ICB exhibited strong abscopal antineoplastic effects on contralateral tumors underlining the potency of this combination therapy.