Genprex, Inc. (“Genprex” or the “Company”) (NASDAQ: GNPX), a clinical-stage gene therapy company, reported that its collaborators from The University of Texas MD Anderson Cancer Center (“MD Anderson”) presented positive preclinical data for the combination of TUSC2 immunogene therapy with an anti-PD1 antibody, pembrolizumab, and for the combination of TUSC2 immunogene therapy, pembrolizumab, and chemotherapy for the treatment of some of the most resistant metastatic lung cancers, including the KRAS and LKB1 mutations, at the American Association of Cancer Research Tumor Immunology and Immunotherapy Meeting 2019. The TUSC2 gene is a tumor suppressor gene and is the active agent in Genprex’s Oncoprex™ immunogene therapy.
The poster, entitled “Efficacy of Novel Immunogene-Combinations for KRAS and LKB1 mutant NSCLC in a Humanized Mouse Model” shows that TUSC2 confers sensitivity to checkpoint blockade for some of the most resistant metastatic human cancers, including the KRAS and LKB1 mutations, in mice with human immune cells (humanized mice) with lung metastases. When TUSC2 was combined with anti-PD1 therapy, pembrolizumab, in humanized mice with KRAS and LKB1 lung metastases, there was significantly increased antitumor activity than when compared to either agent alone. This combination and model also demonstrated TUSC2-related NK (Natural Killer) cell activation. A significantly higher percentage of CD56+ NK and CD56+CD59+ active NK cells, which are immune cells that have been activated to kill cancer cells, were found in the mice that received TUSC2 alone and in those that received the combination of TUSC2 and pembrolizumab than in those that received pembrolizumab alone.
The poster also shows that TUSC2 increases the effectiveness of anti-PD1 checkpoint blockade combined with platinum chemotherapy in humanized mice with lung metastases with KRAS and LKB1 mutations, thus demonstrating that TUSC2 may improve on first-line standard of care for lung cancer. The combination of TUSC2 with pembrolizumab and carboplatin, a platinum chemotherapy, in humanized mice with KRAS and LKB1 lung metastases resulted in metastasis regression significantly greater than either TUSC2 alone or pembrolizumab combined with carboplatin treatments. This model showed significantly fewer or no visible tumor nodules after treatment with the TUSC2 combination as compared with other groups, and it showed strong antitumor efficacy. The combination of TUSC2 with pembrolizumab and carboplatin resulted in complete eradication of anti-PD1 resistant lung metastases in the humanized mouse model.
“These data not only further support existing preclinical data showing that Oncoprex immunogene therapy is synergistic with anti-PD1 therapy, but they also offer new data demonstrating that Oncoprex improves on the combination of anti-PD1 therapy and chemotherapy, today’s first line standard of care for lung cancer,” said Julien L. Pham, MD, MPH, President and Chief Operating Officer of Genprex. “In a sophisticated humanized mouse model, the combination of TUSC2 with pembrolizumab and carboplatin resulted in complete eradication of anti-PD1 resistant lung metastases in some of the most resistant cancer mutations. This is highly encouraging and provides us with a strong indication that the combination could lead to similar results in the clinic.”
The poster authors are Ismail M. Meraz, Mourad Majidi, Meng Feng, RuPing Shao, Min Jin Ha, Jeffrey Morris, Elizabeth J. Shpall, Jack A. Roth, all of MD Anderson Cancer Center, Houston, TX. Jack A. Roth has ownership interest in and is a consultant/advisory board member for Genprex, Inc.
The poster is available on Genprex’s website at genprex.com.