According to the National Cancer Institute, lung cancer is the leading cause of cancer deaths in the United States, killing more people than breast, colon, kidney, liver, and prostate cancers combined, and is the second most common type of cancer. Each year, there are over 1.8 million new lung cancer cases and 1.6 million deaths from lung cancer worldwide, and in the United States there are over 225,000 new cases and more than 150,000 deaths from lung cancer per year. Non-small cell lung cancer (NSCLC) represents 80% of all lung cancer cases.
Systemic, cytotoxic chemotherapy remains a standard treatment for many NSCLC patients. Some patients may benefit from targeted cancer therapies, such as tyrosine kinase inhibitors (TKIs), but the majority of patients are not candidates for these therapies because they do not have the right molecular profile. Additionally, some patients receiving TKIs often see their disease progress as their tumors become resistant to TKI treatment.
More recently, immunotherapies, such as checkpoint inhibitors, have achieved encouraging clinical responses in NSCLC, however, the majority of patients do not respond to checkpoint inhibition.
Growing scientific consensus points to utilizing a combination therapy approach to targeting multiple anti-cancer pathways as the most promising approach to achieving greater response rates in cancer patients.
Immunogene therapy: a multimodal attack on cancer cells
Biotechnology company Genprex, Inc.’s immunogene therapy has the potential to increase the clinical utility of targeted therapies and immunotherapies and expand their use for a larger population of patients.
The company’s lead drug candidate, Oncoprex, consists of a gene called TUSC2 that is encapsulated in a positively charged nanovesicle made from lipid molecules, and is non-viral mediated. The therapy is injected intravenously and is able to home in to target cancer cells, partly due to electrical charge interaction as well as physico-chemical properties of the delivery vector. Once Oncoprex penetrates the cancer cell, the TUSC2 gene is expressed into a protein that corrects certain aberrant functions that allow the cancer cells to proliferate. Oncoprex has a multimodal mechanism of action that interrupts cell-signaling pathways governing replication of cancer cells, re-establishes pathways that induce programmed cell death (or apoptosis) of cancer cells, and marshals the body’s own immune response against cancer cells.
Better Together: Immunogene therapy’s synergistic effect on targeted and immunotherapies
Clinical and preclinical data indicate that Oncoprex works in combination with a number of other anti-cancer therapies including TKIs, such as erlotinib (Tarceva®) and gefitinib (Iressa®), that inhibit the epithelial growth factor receptor (EGFR), the AKT inhibitor MK2206; and checkpoint inhibitors, such as anti-PD1 and CTLA-4 agents, in the same family as pembrolizumab (Keytruda®), nivolumab (Opdivo®), atezolizumab (Tecentriq®), and ipilimumab (Yervoy®).
Research has shown that Oncoprex combined with EGFR TKI therapeutics can overcome tumor resistance by inactivating EGFR and AKT signaling pathways to restore apoptosis. The combination provides a synergistic effect that can potentially benefit patients with EGFR negative status or who have rare mutations typically not responsive to EGFR inhibition. Interim data from the company’s Phase I/II clinical trial evaluating Oncoprex in combination with erlotinib in patients with advanced NSCLC showed a disease control rate of 78%, with seven out of nine patients achieving stable disease or better, including one complete response (CR).
Preclinical research in a NSCLC metastasis mouse model has demonstrated that TUSC2 alone or in combination with anti-PD-1 and/or anti-CTLA4 checkpoint blockade significantly prolonged survival compared to checkpoint blockade alone. The greatest increase in survival was seen with TUSC2 combined with checkpoint blockade and treatment response was associated with high infiltration of natural killer (NK) cells and CD8+ T cells, and low infiltration of myeloid-derived suppressor cells (MDSC) in the tumor microenvironment.
Based on these data, Genprex is expanding its clinical development program to study TUSC2 with checkpoint inhibitors. The goal is to provide a combination cancer treatment that can achieve greater response rates in a larger population of patients.
This article contains forward-looking statements, which are subject to risks and uncertainties, including those described under the caption “Risk Factors” and elsewhere in Genprex’s filings and reports with the United States Securities and Exchange Commission. Actual results may differ materially from those expressed or implied by such forward-looking statements.