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Ref Type Journal Article
PMID (30670061)
Authors Camilio KA, Wang MY, Mauseth B, Waagene S, Kvalheim G, Rekdal Ø, Sveinbjørnsson B, Mælandsmo GM
Title Combining the oncolytic peptide LTX-315 with doxorubicin demonstrates therapeutic potential in a triple-negative breast cancer model.
Journal Breast cancer research : BCR
Vol 21
Issue 1
Date 2019 Jan 22
URL
Abstract Text Immunochemotherapy, the combined use of immunotherapy and chemotherapy, has demonstrated great promise in several cancers. LTX-315 is an oncolytic peptide with potent immunomodulatory properties designed for the local treatment of solid tumors. By inducing rapid immunogenic cell death through the release of danger-associated molecular pattern molecules (DAMPs), LTX-315 is capable of reshaping the tumor microenvironment, turning "cold" tumors "hot" through a significant increase in tumor-infiltrating lymphocytes.We investigated the potential of LTX-315 to be used in combination with standard-of-care chemotherapy (doxorubicin, brand name CAELYX®) against triple-negative breast cancer in an orthotopic 4 T1 mammary fat pad model. Tumor growth curves were compared using one-way ANOVA analysis of variance and Tukey's multiple comparisons test, and animal survival curves were compared using the log-rank (Mantel-Cox) test. We considered p values ≤0.05 to indicate statistical significance.We found that LTX-315 displayed a strong additive antitumoral effect when used in combination with CAELYX®, and induced immune-mediated changes in the tumor microenvironment, followed by complete regression in the majority of animals treated. Furthermore, imaging techniques and histological examination showed that the combination induced strong local necrosis, followed by an increase in the infiltration of CD4+ and CD8+ immune cells into the tumor parenchymal tissue.Our data demonstrate that LTX-315 is a promising combination partner with CAELYX® for the treatment of triple-negative breast cancer.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
LTX-315 LTX-315 0 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
LTX-315 LTX-315 is a 9-mer oncolytic peptide that induces release of danger-associated molecular pattern molecules (DAMPs), and may increase anti-tumor immune response and decrease tumor growth (PMID: 26982623, PMID: 30670061).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown triple-receptor negative breast cancer not applicable LTX-315 + Pegylated liposomal-doxorubicin Preclinical - Cell line xenograft Actionable In a preclinical study, treatment with the combination of LTX-315 and Doxil (pegylated liposomal doxorubicin) resulted in increased tumor growth inhibition and regression, increased tumor necrosis, and increased T-cell infiltration in triple-negative breast cancer (TNBC) cell line xenograft models compared to either agent alone, and in TNBC models in the neoadjuvant setting induced tumor regression in 50% and improved survival compared to either agent alone (PMID: 30670061). 30670061