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 |
NEW YORK, April 1, 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 “Frontiers in Cancer Immunotherapy” being held on May 14-15, 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.
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, “CELL-FREE TUMOR DNA AND NEUTROPHIL EXTRACELLULAR TRAPS AS NOVEL THERAPEUTIC TARGETS FOR PANCREATIC CANCER” at the Frontiers in Cancer Immunotherapy organized by the New York Academy of Sciences May 14-15, 2019, in New York, New York.
NEW YORK, NY / May 14, 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 on its AAV therapy clinical candidate, CLS-014, this week at the annual meeting of the American Society of Gene and Cell Therapy (ASGCT).