Tumor lysis with LTX-401 creates anticancer immunity
AuthorXie, Wei; Mondragon, Laura; Mauseth, Brynjar; Wang, Yan; Pol, Jonathan; Levesque, Sarah; Zhou, Heng; Yamazaki, Takahiro; Eksteen, Jacobus Johannes; Zitvogel, Laurence; Sveinbjørnsson, Baldur; Rekdal, Øystein; Kepp, Oliver; Kroemer, Guido
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.
This is an Accepted Manuscript of an article published by Taylor & Francis in Oncoimmunology on 13 April 2019, available online: https://www.tandfonline.com/doi/full/10.1080/2162402X.2019.1594555.