NEW YORK, NY / July, 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).
Abstract Title (e16002): Neutrophil extracellular traps blockade in combination with PD-1 inhibition in treatment of colorectal cancer metastasis
Session: Cancer – Targeted Gene and Cell Therapy
Publication: J. Clinical Oncology
Speaker: George Tetz, M.D., Ph.D., CEO of CLS-Therapeutics, Inc
Background: Immune checkpoint inhibitors (ICIs) are currently approved for microsatellite instability-high metastatic colorectal cancer (mCRC) however reported objective response rate to monotherapy range between 28-52%. Neutrophil Extracellular Traps (NETs), an extracellular network of DNA and proteins expelled by neutrophils into the tumor microenvironment, promote CRC metastasis by inducing potent immunosuppressive effects. We hypothesize that targeting this network may improve response rates to immune checkpoint therapy. The purpose of our study is to investigate the effect of combination DNase I treatment, a NET depleting agent, and PD-1 blockade in mCRC progression.
Methods: Subcutaneous MC38 (MSI-H adenocarcinoma of the colon) tumors were established in 6-week-old mice. Treatment was initiated six days after tumor inoculation with daily intraperitoneal (i.p) injections of DNase I followed by i.p anti-PD-1 treatment administered every 3 days. Animals were divided into treatment groups: control, DNase alone, anti-PD-1 alone and combination of DNase I with anti-PD-1 (n = 6 mice/ group).
Results: Tumors were successfully established after 6 days of inoculation. These tumors expressed high neutrophil infiltration and NETs. To determine the effects of combination therapy on tumor progression, we measured tumor volume and time to progression (TTP). We found that mice treated with combination DNase I and anti-PD-1 had significantly lower mean tumor volume compared to anti-PD-1 alone (1372.68mm3 vs 2193.20 mm3, p-value = 0.043). TTP was higher in the combination group compared to anti-PD-1 treatment alone (median time to progression 22 vs 17 days, p-value = 0.004). Next we sought to determine the mechanism behind this effect by investigating if NETs blockade modulated the tumor microenvironment. We found that treatment with DNase I decreased exhaustion of CD8+ T-cells in the tumor compared to no treatment.
Conclusions: Targeting NETs in combination with immune checkpoint inhibition may be an option to improve response rate to immune checkpoint inhibitors through decreasing exhausted CD8+ T-cells.
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.
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).
NEW YORK, March 28, 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 “Targeting Tumor Heterogeneity” being held on May 8, 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.