Scientists investigate NPRL2 gene therapy for hard-to-treat lung cancer—What they found

A significant study published in eLife suggests that NPRL2 gene therapy could offer a new therapeutic approach for treating anti-PD1 resistant non-small cell lung cancer (NSCLC). Conducted by research collaborators at a leading cancer center in Houston, Texas, the study demonstrated that NPRL2 exhibited strong single-agent activity against treatment-resistant NSCLC in humanized mouse models.

The research also highlights the potential of Genprex, Inc.’s (NASDAQ: GNPX) Oncoprex Delivery System, a non-viral lipid nanoparticle platform designed to deliver tumor suppressor genes directly to cancer cells. While NPRL2 gene therapy is not developed by Genprex, the company’s delivery system played a critical role in the study, demonstrating its ability to transport tumor suppressor genes effectively into resistant lung cancer cells.

What Did the Study Reveal About NPRL2 Gene Therapy?

The study focused on KRAS/STK11 mutant anti-PD1 resistant NSCLC, a particularly aggressive and treatment-resistant form of lung cancer. Researchers examined the effects of NPRL2 gene therapy as a standalone treatment and in combination with pembrolizumab (Keytruda), an FDA-approved immune checkpoint inhibitor.

The results were notable: NPRL2 alone triggered a dramatic antitumor response, while pembrolizumab alone was ineffective. The combination of both treatments did not significantly improve outcomes beyond NPRL2 alone, indicating that NPRL2 gene therapy may provide therapeutic benefits independent of checkpoint inhibition.

Further analysis revealed that NPRL2 exerts its effects by activating the immune system, particularly through dendritic cell-mediated antigen presentation and cytotoxic immune cell activation. The study found that the antitumor response was more pronounced in humanized mouse models, reinforcing the immune-modulating properties of NPRL2 therapy.

How Does Genprex’s Oncoprex Delivery System Support Gene Therapy?

The study utilized Genprex’s Oncoprex Delivery System, a proprietary non-viral lipid nanoparticle platform that enables the intravenous delivery of tumor suppressor genes. This technology differs from viral-based gene therapies, which often pose safety concerns such as immune system complications and toxicity risks.

Genprex originally developed the Oncoprex Delivery System for Reqorsa Gene Therapy (quaratusugene ozeplasmid), which delivers the TUSC2 tumor suppressor gene to lung cancer cells. The findings from this study suggest that the platform is versatile enough to deliver other tumor suppressor genes, including NPRL2, broadening its potential clinical applications.

Previous research at MD Anderson Cancer Center demonstrated that Reqorsa Gene Therapy specifically targets tumor cells while minimizing uptake by normal tissues. In preclinical studies, the uptake of TUSC2 in tumor cells after Reqorsa treatment was 10 to 33 times greater than in normal cells, reinforcing the precision of the Oncoprex Delivery System.

What Does This Mean for Lung Cancer Patients?

The study’s findings offer renewed hope for lung cancer patients who have developed resistance to immune checkpoint inhibitors like pembrolizumab. While checkpoint inhibitors have revolutionized NSCLC treatment, many patients fail to respond, particularly those with KRAS/STK11 mutations, which are found in approximately 30% of all NSCLC cases.

The ability of NPRL2 gene therapy to activate an antitumor immune response in these difficult-to-treat tumors suggests that it could serve as an effective treatment option for patients with limited alternatives. If further studies confirm its effectiveness, NPRL2 therapy could potentially be integrated into future clinical trials for drug-resistant lung cancer.

What Are the Next Steps for NPRL2 Gene Therapy Research?

Following the promising preclinical findings, additional clinical research will be necessary to evaluate NPRL2 gene therapy’s safety and efficacy in human patients. While Genprex has not announced any plans to incorporate NPRL2 into its current clinical pipeline, its Oncoprex Delivery System continues to support gene therapy advancements in oncology.

Genprex’s lead gene therapy candidate, Reqorsa, has already received Fast Track Designation from the U.S. Food and Drug Administration (FDA) for NSCLC and Orphan Drug Designation for small cell lung cancer (SCLC). These regulatory designations provide a pathway for expedited development of gene therapies targeting lung cancer.

Beyond oncology, Genprex is also advancing gene therapy for diabetes, using an AAV vector to deliver Pdx1 and MafA genes to the pancreas. This technology has demonstrated the ability to transform alpha cells into insulin-producing beta-like cells, offering a potential new treatment strategy for Type 1 and Type 2 diabetes.

Could NPRL2 Gene Therapy Change the Future of Lung Cancer Treatment?

The potential of NPRL2 gene therapy represents a major advancement in the fight against drug-resistant lung cancer. While immune checkpoint inhibitors have transformed lung cancer care, their effectiveness remains limited to a subset of patients. The development of tumor suppressor gene therapy, delivered through non-viral platforms like Oncoprex, provides a promising alternative for those who do not respond to current treatments.

As researchers continue to explore NPRL2 gene therapy, its ability to trigger immune system activation and tumor suppression could make it a valuable addition to future cancer treatment strategies. With continued scientific investigation and clinical trials, this innovative approach has the potential to improve outcomes for thousands of lung cancer patients worldwide.