LTX-315, a novel oncolytic peptide is effective against both drug-resistant and drug-sensitive cancer cells with lower toxicity towards normal cells. Intratumoral treatment with LTX-315 results in growth inhibition, complete regression and long lasting tumor-specific immune responses.
The oncolytic effect of LTX-315 involves perturbation of the plasma membrane and distortion of intracellular organelles including the mitochondria with subsequent release of Damage-Associated Molecular Pattern molecules (DAMPs) such as ATP, cytochrome c and HMGB1. LTX-315 effectively induces necrosis within the tumor followed by the release of tumor antigens as demonstrated by a greater increase in tumor infiltrating CD8+ T cells, expansion of T cell clonality, and number of clones within the tumor microenvironment.
LTX-315`s ability to modify the tumor microenvironment makes it ideal as a combination partner for other cancer therapies, including chemotherapy and immune checkpoint inhibitors.
In preclinical tumor models, combination of LTX-315 and chemotherapeutic agents such as cyclophosphamide and doxorubicin demonstrates significant synergy.
Citation Format: Ketil André Camilio, Meng Yu Wang, Janne Nestvold, Gunhild Mælandsmo, Baldur Sveinbjørnsson, Øystein Rekdal. The oncolytic peptide LTX-315 enhances T cell clonality and induces synergy with chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 11. doi:10.1158/1538-7445.AM2017-11