Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Πέμπτη 4 Φεβρουαρίου 2021

Safety, anti-tumor activity and T-cell responses in a dose-ranging phase 1 trial of the oncolytic peptide LTX-315 in patients with solid tumors

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Purpose: LTX-315 is a first in class, 9-mer membranolytic peptide that has shown potent immunomodulatory properties in preclinical models. We conducted a phase 1 dose-escalating study of intratumoral LTX-315 administration in patients with advanced solid tumors. Patient and methods: Thirty-nine patients were enrolled, receiving LTX-315 injections into accessible tumors. The primary objective was to assess the safety and tolerability of this approach, with anti-tumor and immunomodulatory activity as secondary objectives. Tumor biopsies were collected at baseline and post-treatment for analysis of immunological parameters. Results: The most common treatment-related grade 1-2 adverse events were vascular disorders including transient hypotension (18 patients, 46%), flushing (11 patients, 28%), and injection site reactions in 38% of patients. The most common grade 3 LTX-315-related toxicities were hypersensitivity or anaphylaxis (4 patients, 10%). Analysis of im mune endpoints in serial biopsies indicated that LTX-315 induces necrosis and CD8+ T cell infiltration into the tumor microenvironment. Sequencing of the TCR repertoire in peripheral blood identified significant expansion of T-cell clones after treatment, of which 49% were present in available tumor biopsies after treatment, suggesting that they were tumor-associated. Substantial volume reduction ({greater than or equal to}30%) of injected tumors occurred in 29% of the patients, and 86% (12 out of 14 biopsies) had an increase in intralesional CD8+ T cells post-treatment. No partial responses by immune-related response criteria were seen, but evidence of abscopal effect was demonstrated following treatment with LTX-315. Conclusions: LTX-315 has an acceptable safety profile, is clinically active, induces changes in the tumor microenvironment and contributes to immune-mediated anticancer activity.

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