Xenetic Biosciences, Inc. Presents Positive Data Demonstrating DNase I Significantly Improves Efficacy of Anti-CTLA-4 Immune Checkpoint Blockade in Preclinical Colorectal Carcinoma Models

In This Article:

Data presented at Society for Immunotherapy of Cancer (SITC) 2024

Systemic DNase I combined with 𝛼-CTLA-4 antibody demonstrated to promote antitumor immunity and generate immunological memory against microsatellite stable, mismatch repair proficient colorectal carcinoma (CRC) tumors

FRAMINGHAM, MA / ACCESSWIRE / November 12, 2024 / Xenetic Biosciences, Inc. (NASDAQ:XBIO) ("Xenetic" or the "Company"), a biopharmaceutical company focused on advancing innovative immuno-oncology technologies addressing hard to treat oncology indications, today announced the presentation of positive preclinical data.

The poster titled, " DNase I Targeting of Neutrophil Extracellular Traps Improves CTLA-4 Immune Checkpoint blockade in Models of MSS/MMRp CRC ," was presented byReid Bissonnette, Ph.D., Executive Consultant for Translational Research and Development at Xenetic at the Society for Immunotherapy of Cancer (SITC) 39 th Annual Meeting held on November 6-10, 2024, in Houston, Texas and virtually.

"We continue to be encouraged by the data demonstrated by our DNase platform technology. Several human cancers, including gastrointestinal cancers like colorectal cancers (CRC) in particular, have high levels of neutrophil infiltration and neutrophil extracellular traps (NETs), which contribute to an immunosuppressive, protumor microenvironment (TME), leading to poor response to therapies. Based on the growing body of data, we believe our DNase-based oncology platform has the potential to address the significant unmet need across a number of cancer indications where immune checkpoint inhibitors have not shown significant clinical utility to date, such as microsatellite stable, mismatch repair proficient (MSS/MMRp) CRC, which is the largest subset of CRC and where immune checkpoint inhibitors have shown little clinical efficacy. We look forward to continuing our efforts to advance this important program toward clinical-stage," commented Dr. Bissonnette.

For the preclinical study, mice were implanted with either CT26 or Colon26 cells, both mouse models of MSS/MMRp CRC. The mice were treated with anti-CTLA-4 and either daily or biweekly DNase I (administered either ip or iv). Response was monitored by measuring tumor volume.

Key Highlights

  • Data demonstrates beneficial effects of targeting NETs with systemic DNase I in models of primary tumor and metastatic CRC, improving the efficacy of CTLA-4 immune checkpoint blockade.

  • Both published and newer data suggests that DNase I impedes neutrophil tumor infiltration, promotes CD4 and CD8 T cell infiltration, and enhances intratumoral T cell activation.

  • DNase I plus 𝛼-CTLA-4 combination therapy results in tumor growth inhibition, several CRs and enhanced survival in mice bearing CT26 or Colon26 MSS/MMRp CRC tumors.

  • Dose response evaluations of DNase I combined with 𝛼-CTLA-4, examining both route and frequency of administration was performed.

  • DNase I plus 𝛼-CTLA-4 combination therapy resulted in complete responses (CRs) in mice bearing either CT26 or Colon26 tumors.

  • Significantly, rechallenge of Colon26 and CT26 complete responder animals resulted in no (0 mm3) tumor take or growth, suggesting that DNase I combined with 𝛼-CTLA-4 promoted antitumor immunity and immunological memory.

Waiting for permission
Allow microphone access to enable voice search

Try again.