On April 20, 2026 Genprex, Inc. ("Genprex" or the "Company") (NASDAQ: GNPX), a clinical-stage gene therapy company focused on developing life-changing therapies for patients with cancer and diabetes, reported that its research collaborators presented at the 2026 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting being held April 17-22, 2026 in San Diego, California. The collaborators presented positive preclinical data from studies of its lead drug candidate, Reqorsa Gene Therapy (quaratusugene ozeplasmid, also referred to as Quar Oze), for the treatment of lung cancer.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"The identification of TROP2 and PTEN as potential biomarkers for primary resistance to REQORSA may provide invaluable insights for patient selection, enhancing our precision medicine strategy for our lung cancer clinical trials," said Ryan Confer, President and Chief Executive Officer at Genprex. "Furthermore, the demonstrated ability of REQORSA to induce apoptosis and decrease tumor volume in ALK-EML4 positive NSCLC cell lines and in vivo models, including those resistant to current ALK inhibitors such as alectinib, represents a potential opportunity for a future clinical trial. In addition, REQORSA’s capacity to boost Natural Killer cell antitumor activity and immunity led to observed tumor suppression and even complete tumor elimination in preclinical studies. This demonstrates REQORSA’s potential not only as a standalone agent, but also as a powerful adjunct therapy to re-sensitize resistant tumors and improve outcomes for a broad spectrum of lung cancer patients."
The featured Genprex-supported abstracts and posters presented at AACR (Free AACR Whitepaper) 2026:
Title: "TROP2 and PTEN are biomarkers of primary resistance to TUSC2 gene therapy in non-small cell lung cancer (NSCLC)"
Session Category: Experimental and Molecular Therapeutics
Session Title: Mechanisms of Drug Resistance 1
Session Date and Time: April 19, 2026 from 2-5 p.m. PT
Location: Poster Section 16
Poster Board Number: 24
Abstract Presentation Number: 391
In this study, researchers established models primarily resistant to TUSC2 gene therapy (REQORSA or Quar Oze) to find biomarkers indicative of TUSC2 gene therapy resistance in NSCLC cell lines, PDX-derived organoids (PDXOs), and patient-derived xenografts (PDXs). A panel of 10 NSCLC cell lines screened for TUSC2 sensitivity showed resistance in 50% of the cell lines, as assessed by annexin V staining and colony formation assays. Researchers evaluated TUSC2 sensitivity in 12 NSCLC PDXOs using ATP-based viability assays in 3D culture following TUSC2 or empty vector transfection. While some PDXOs were highly responsive to TUSC2 within 72 hours post-transfection, 50% of PDXOs exhibited primary resistance. TC314AR (Acquired Resistance) PDX tumors and xenograft models (A549AR, H1299AR, H23AR) were developed, grown in NSG mice, and then treated with TUSC2 gene therapy. 20-30% of tumors in every model showed resistance, with no significant reduction in size compared to the control tumors after treatment. Protein expression profiling using reverse-phase protein array (RPPA) analysis of 500 proteins showed distinct expression signatures, with several candidate biomarkers significantly altered in resistant cell lines and PDXOs. RPPA analysis of residual tumors from both the xenograft and PDX models revealed significant but model-specific alterations in protein expression between responders and non-responders. Comparative analyses across the three models showed low expression of TROP2 and high expression of PTEN as potential biomarkers of primary resistance. Overexpression of TROP2 in H1299 and H460 cells increased TUSC2-induced apoptosis. These findings suggest that TROP2 and PTEN may serve as biomarkers to predict TUSC2 response and guide therapeutic strategies in NSCLC.
Title: "Quaratusugene ozeplasmid mediated TUSC2 upregulation in EML4-ALK bearing non-small cell lung carcinoma induces apoptosis and is highly effective in preclinical studies"
Session Category: Experimental and Molecular Therapeutics
Session Title: RNA, Gene and Cell Therapies, and Enabling Assay Technologies
Session Date and Time: April 19, 2026 from 2-5 p.m. PT
Location: Poster Section 19
Poster Board Number: 12
Abstract Presentation Number: 469
In this study, researchers evaluated TUSC2 expression in a range of ALK+ cell lines and patient-derived organoids (PDOs), both prior to and following exposure to quaratusugene ozeplasmid (Quar Oze). The findings show that Quar Oze-driven TUSC2 overexpression initiates a robust pro-apoptotic response in ALK-positive (ALK+) models, not only in cells that are sensitive but also with acquired resistance (generated in the lab) to the ALK inhibitor alectinib. This is evidenced by increased pro-apoptotic markers and lower cell viability when Quar Oze is used in combination with alectinib. To further assess the Quar Oze and alectinib combination, researchers tested it in two in vivo models: (1) an alectinib-sensitive model using subcutaneous injection of NCI-H2228 ALK+ cells into nude mice, and (2) an alectinib-resistant model using ALK167 PDX implants in NSG mice. Once tumors reached ~ 100 mm³, mice were randomized into four groups: vehicle control; Quar Oze alone (25 μg/mouse, IV, every three days); alectinib alone (0.5 mg/kg for sensitive or 15 mg/kg for resistant, oral, daily); and Quar Oze plus alectinib at the same doses. In the sensitive model, tumors in the alectinib-treated group shrank by 60%. Notably, treatment with Quar Oze alone, and particularly Quar Oze combined with alectinib, resulted in 79% tumor shrinkage (p value 0.0135 versus control), demonstrating a 23% improved outcome compared to alectinib alone. This suggests that Quar Oze might serve as a valuable adjunct therapy, especially for patients who have advanced disease and/or experience resistance to TKIs.
In the resistant model, the Quar Oze and alectinib combination produced a synergistic effect, achieving the greatest tumor reduction and improved overall survival (p value 0.0001 versus control), further supporting the clinical potential of this therapeutic strategy in ALK+ NSCLC. Altogether, the in vitro and in vivo studies indicate that Quar Oze-mediated TUSC2 overexpression in ALK+ NSCLC effectively curtails tumor growth and proliferation via activation of apoptotic pathways, providing a compelling rationale for progressing toward a clinical trial.
Title: "Restoring TUSC2 function boosts NK cell cytotoxicity and antitumor immunity in vivo and in vitro"
Session Category: Immunology
Session Title: Immune Cell Biology and Tumor-Immune Crosstalk
Session Date and Time: April 19, 2026 from 2-5 p.m. PT
Location: Poster Section 8
Poster Board Number: 7
Abstract Presentation Number: 164
TUSC2, located on chromosome 3p21.3, is frequently deleted in multiple human cancers, including NSCLC, small cell lung carcinoma (SCLC), mesothelioma, breast cancer and head-and-neck cancers. Loss of TUSC2 is associated with reduced survival and increased tumor aggressiveness. Although TUSC2 is known to suppress tumor cell proliferation and induce apoptosis, its regulatory role in the immune system—particularly in innate lymphoid populations—remains insufficiently defined. Building on prior work identifying TUSC2 as a mitochondrial protein involved in calcium regulation and immune modulation, researchers hypothesized that TUSC2 exerts antitumor effects in part by enhancing NK cell cytotoxicity.
Tusc2 knockout (Tusc2 KO) and wild-type (Tusc2 WT) mice were challenged with syngeneic tumor cells (344SQ) and treated with TUSC2-expressing lipoparticles (quaratusugene ozeplasmid, Quar Oze). The therapeutic group received Quar Oze after tumor establishment starting at day 8 from cell line injection, while the prophylaxis group received Quar Oze before tumor establishment, starting 2 days before injection of cell lines. Control groups received empty lipoparticles. After three weeks from cell line injection, tumor volumes were assessed, and mice were euthanized for collection of tumors, spleens, and tumor-draining lymph nodes (TDLN). Immune cell phenotypes and cytotoxic markers were analyzed using flow cytometry.
In vitro studies evaluated NK cell cytotoxic function following Quar Oze treatment by measuring CD107a degranulation and CellTrace Violet–based proliferation. In the therapeutic treatment group, 67% of Tusc2 KO mice and 33% of Tusc2 WT mice achieved complete tumor regression, with all remaining mice showing significant tumor reduction compared with controls. Prophylactic administration did not induce complete tumor clearance but consistently reduced tumor growth across all mice. Immune profiling of the tumor microenvironment revealed that Quar Oze robustly enhanced NK cell cytotoxicity, particularly increasing granzyme B and perforin expression. In vitro assays confirmed that TUSC2 restoration significantly increased NK cell degranulation and proliferation, supporting the in vivo findings.
In conclusion, TUSC2 acts as a critical enhancer of innate antitumor immunity by boosting NK cell cytotoxic function. Therapeutic delivery of TUSC2 via Quar Oze suppresses tumor progression and, in many cases, drives complete tumor elimination. These results highlight TUSC2 as a potent immunomodulatory tumor suppressor and support its development as a dual-function therapeutic that directly targets tumor cells while also activating NK cell–mediated immunity.
These AACR (Free AACR Whitepaper) 2026 posters have been made available on Genprex’s website.
(Press release, Genprex, APR 20, 2026, View Source [SID1234664538])