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.
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.
NEW YORK, NY / April 06, 2021 / CLS Therapeutics, cancer gene therapy company utilizing a novel therapeutic target, announces presentation at the upcoming 2021 American Society of Gene & Cell Therapy (ASGCT) 24th Annual Meeting.
NEW YORK, NY / April 08, 2020 / CLS Therapeutics, a privately held anticancer gene therapy platform company addressing a novel therapeutic target, announces presentation at the upcoming 2020 American Society of Gene & Cell Therapy (ASGCT) Annual Meeting that will be held from April 29 to May 2, 2019 that is planned to be held May 12 – May 15, 2020, at the Hynes Convention Center in Boston, USA.