MiNA Therapeutics Presents Pre-Clinical Data Supporting Combination of MTL-CEBPA with Sorafenib and Other Cancer Treatments at AACR.
M2 PHARMA-April 3, 2019-MiNA Therapeutics Presents Pre-Clinical Data Supporting Combination of MTL-CEBPA with Sorafenib and Other Cancer Treatments at AACR
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- UK-based RNA activation therapeutics specialist MiNA Therapeutics has released pre-clinical data supporting the immunological effects of MTL-CEBPA and its benefits in combination with other anti-cancer interventions including sorafenib, anti-PD1 checkpoint inhibition and radiofrequency ablation, the company said.
The data will be presented in two posters at the 2019 American Association for Cancer Research annual meeting taking place in Atlanta, Georgia.
MiNA Therapeutics said the first pre-clinical study highlights that the combination of MTL-CEBPA with sorafenib resulted in superior tumour growth inhibition and reduction of tumour biomarker alpha-fetoprotein compared to single agents as demonstrated in an immunocompetent rat model of hepatocellular carcinoma.
The anti-tumour activity of sorafenib had previously been demonstrated to be enhanced by immunological agents targeting suppressive myeloid cells in the tumour microenvironment.
In the presented study, the combination of MTL-CEBPA and sorafenib was administered in a sequential regimen to "prime" tumours with MTL-CEBPA before treating with sorafenib. Most importantly, the results further support the expansion of MiNA's Phase 1b OUTREACH trial to evaluate MTL-CEBPA in combination with sorafenib.
A second pre-clinical study describes a triple combination of MTL-CEBPA with anti-PD1 checkpoint inhibition and radiofrequency ablation in an immunocompetent mouse model of liver cancer bearing tumours on two opposite flanks.
Radiofrequency ablation was performed on one flank only and treatment effects were assessed on the contralateral flank. Compared to single agent or double combinations, the triple combination demonstrated significantly improved immunological responses as well as anti-tumour activity.
Immunological responses in the tumour microenvironment were evidenced by superior infiltration of cytotoxic T lymphocytes as well as natural killer T cells. Anti-tumour activity was evidenced by near complete inhibition of tumour growth including complete responses.
Improved tumour growth inhibition in the contralateral flank suggested that the combination of MTL-CEBPA and anti-PD1 checkpoint inhibition increased the effectiveness of the abscopal effects of radiofrequency ablation.
MTL-CEBPA consists of a double stranded RNA formulated in a liposomal nanoparticle and is designed to activate the CEBPA gene. The CEBPA gene encodes CCAAT/enhancer binding protein alpha (C/EBP-?), a transcription factor that acts as a master regulator of cell lineage determination and differentiation in several tissues including myeloid cells, liver cells and adipose tissue.
In cancer, C/EBP-? plays important roles in regulating both tumour growth and the tumour immune microenvironment. MTL-CEBPA is currently under evaluation in OUTREACH, a Phase Ib clinical study in patients with advanced liver cancer.
The multi-centre study is assessing the safety, tolerability and anti-tumour activity of MTL-CEBPA in combination with sorafenib.
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|Date:||Apr 3, 2019|
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