Sep 09, 2020
CLS’s AAV‐mediated Gene Transfer of DNase I Study in Colorectal Cancer Published in the Journal, Molecular Oncology

NEW YORK, NY /  September, 2020 / CLS Therapeutics, a preclinical-stage anticancer gene therapy platform company developing novel medicines to bring the curative power of cell-free DNA destruction to patients with tumors, presented preclinical data at the annual meeting of the American Society of Clinical Oncology (ASCO).

AAV‐mediated gene transfer of DNase I in the liver of mice with colorectal 
cancer reduces liver metastasis and restores local innate and adaptive immune response 
Publication Type  Journal article
 Authors
 Abstract Liver metastasis is the main cause of colorectal cancer (CRC)‐related death. Neutrophil extracellular traps (NETs) play important roles in CRC progression. Deoxyribonuclease I (DNase I) has been shown to alter NET function by cleaving DNA strands comprising the NET backbone. Moreover, DNase I displays high antimetastatic activity in multiple tumor models. To circumvent long‐term daily administrations of recombinant DNase I, we have developed an adeno‐associated virus (AAV) gene therapy vector to specifically express DNase I in the liver. In this study, we demonstrate AAV‐mediated DNase I liver gene transfer following a single intravenous injection suppresses the development of liver metastases in a mouse model of CRC liver metastasis. Increased levels of neutrophils and NET formation in tumors are associated with poor prognosis in many patients with advanced cancers. Neutrophil infiltration and NET formation were inhibited in tumor tissues with AAV‐DNase I treatment. This approach restored local immune responses at the tumor site by increasing the percentage of CD8+ T cells while keeping CD4+ T cells similar between AAV‐DNase I and AAV‐null treatments. Our data suggest that AAV‐mediated DNase I liver gene transfer is a safe and effective modality to inhibit metastasis and represents a novel therapeutic strategy for CRC.
Year of
Publication
 2020
 Journal Molecular Oncology
 DOI 10.1002/1878-0261.12787
May 10, 2019

CLS Therapeutics Inc., a preclinical-stage biopharmaceutical company developing next-generation gene therapy anticancer drugs, today announced that George Tetz, MD, Ph.D., Chief Executive Officer, presented the poster, “TRANSFORMATIVE ANTICANCER GENE THERAPY PLATFORM ADDRESSING A NOVEL THERAPEUTIC TARGET” at the Targeting Tumor Heterogeneity Conference organized by the New York Academy of Sciences May 8, 2019, in New York, New York.

May 10, 2019

CLS Therapeutics Inc., a preclinical-stage biopharmaceutical company developing next-generation gene therapy anticancer drugs, today announced that George Tetz, MD, Ph.D., Chief Executive Officer, presented the poster, “TRANSFORMATIVE ANTICANCER GENE THERAPY PLATFORM ADDRESSING A NOVEL THERAPEUTIC TARGET” at the Cancer Metabolism and Signaling organized by the New York Academy of Sciences May 9, 2019, in New York, New York.

Mar 29, 2019

NEW YORK, March 29, 2019 – CLS Therapeutics, Inc., today announced a poster presentation “First-In-Class-AAV-Based Gene Therapy For Pancreatic Cancer Based On The Destruction Of Cell-Free DNA with Vector-delivered DNase I” at the New York Academy of Sciences symposium “Cancer Metabolism and Signaling” being held on May 9, 2019, in New York City. The presentation includes the first animal data for the activity of AAV-based vector (in silico designed ) encoding DNase I of the treatment of pancreatic cancer animal model.