The oncolytic peptide LTX-315 overcomes resistance of cancers to immunotherapy with CTLA4 checkpoint blockade View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-06

AUTHORS

T Yamazaki, J M Pitt, M Vétizou, A Marabelle, C Flores, Ø Rekdal, G Kroemer, L Zitvogel

ABSTRACT

Intratumoral immunotherapies aim at reducing local immunosuppression, as well as reinstating and enhancing systemic anticancer T-cell functions, without inducing side effects. LTX-315 is a first-in-class oncolytic peptide-based local immunotherapy that meets these criteria by inducing a type of malignant cell death that elicits anticancer immune responses. Here, we show that LTX-315 rapidly reprograms the tumor microenvironment by decreasing the local abundance of immunosuppressive Tregs and myeloid-derived suppressor cells and by increasing the frequency of polyfunctional T helper type 1/type 1 cytotoxic T cells with a concomitant increase in cytotoxic T-lymphocyte antigen-4 (CTLA4) and drop in PD-1 expression levels. Logically, in tumors that were resistant to intratumoral or systemic CTLA4 blockade, subsequent local inoculation of LTX-315 cured the animals or caused tumor regressions with abscopal effects. This synergistic interaction between CTLA4 blockade and LTX-315 was reduced upon blockade of the β-chain of the interleukin-2 receptor (CD122). This preclinical study provides a strong rationale for administering the oncolytic peptide LTX-315 to patients who are receiving treatment with the CTLA4 blocking antibody ipilimumab. More... »

PAGES

1004-1015

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/cdd.2016.35

DOI

http://dx.doi.org/10.1038/cdd.2016.35

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1037749715

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27082453


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