Genprex : AACR 2026 Poster - Restoring TUSC2 function boosts NK cell cytotoxicity and antitumor immunity in vivo and in vitro

Published: 2026-04-19 18:12:04 ET GNPX

Published on 04/19/2026 at 06:12 pm EDT

Muna Mohammed1, Salvador Gonzalez Ochoa2, Jane Tonello2, Thanigaivelan Kanagasabai2, Mark Berger3, Alla Ivanova2*, Anil Shanker1,2*

1School of Graduate Studies, Meharry Medical College, Nashville, TN 2Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, Meharry Medical College, Nashville, TN, 3Genprex, Austin, TX

Tumor Suppressor Candidate 2 (TUSC2), located on chromosome 3p21.3, is A B

frequently deleted in multiple human cancers, including non-small cell lung

carcinoma (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 our prior work identifying TUSC2 as a mitochondrial protein involved in calcium regulation and immune modulation, we hypothesized that TUSC2 exerts antitumor effects in part by enhancing NK cell cytotoxicity.

Figure 1: A schematic showing the importance of calcium in cytotoxic NK cell signaling

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Explore the anti-tumor effect of TUSC2, leveraging the Tusc2 KO mouse model and TUSC2 expressing lipoparticles (Quar Oze)

Investigate the tumor microenvironment in mice that received

TUSC2 supplementation versus the control group

Study cytotoxic immune cells, specifically NK cells, in vitro to

identify the effect of Quar Oze on cytotoxic granules.

Figure 4: A, B. Treatment with TUSC2 lipoparticles (Quar Oze) significantly reduced tumor volume in both Tusc2 WT and KO mice. C. in vitro coculture of WT/ KO NK cell with 344SQ cell lines showed that Tusc2 WT mice are more

C

capable to degranulate compared with Tusc2 KO NK cells.

Figure 5: TUSC2 boosts cytotoxic molecules production. A. Gating strategy for NK cells from CD3- populations. B. Treatment with TUSC2 lipoparticles increases the expression of Granzyme-B and perforin in cytotoxic cells. C. representative figure for KO mice bearing a tumor, treated with Quar Oze versus control

Direct cytotoxicity mediated by NK cells exerts significant anticancer effects (Chu et al, 2022). NK cells kill cancer cells directly through various mechanisms: (1) NK cells release the cytotoxic molecules, perforin and granzyme to cause apoptosis of malignant cells. (2) NK cells trigger apoptosis through the binding of membrane TNF family molecules to tumor cell membrane ligands. (3) antibody-dependent cell-mediated cytotoxicity (ADCC). (4) NK cells generate plenty of cytokines like IFN-y that exert anti-tumor effects

A

Meraz et al, 2018 showed earlier that the anti-tumor effect of TUSC2 was mainly attributed to NK cells. .

Figure 2: A. Injection schedule of mice with 344SQ cell lines and injection with TUSC2 lipoparticles (Quar Oze). B. Purification of Tumor-infiltrating leukocytes (TILs) and their phenotyping using flow cytometry

Figure 3: NK cell harvesting, purification and co-culture with 344SQ cell line

Figure 6 TUSC2 is needed for proper NK cell proliferation. A. Gating strategy for NK cells from CD3- populations. B. Tusc2 KO cells failed to reach generation 6 of proliferation. C. Significant difference between Tusc2 WT NK and Tusc2 KO NK in proliferation capacity.

Ivanova AV, et al. Autoimmunity, spontaneous tumourigenesis, and IL-15 insufficiency in mice with a targeted disruption of the tumour suppressor gene Fus1. PMID: 17318811.

Kondo M, et al. Overexpression of candidate tumor suppressor gene FUS1 isolated from the 3p21.3 homozygous deletion region leads to G1 arrest and growth inhibition of lung

cancer cells. Oncogene. PMID: 11593436.

Arrigo A, et al. Tumor Suppressor Candidate 2 (TUSC2): Discovery, Functions, and Cancer Therapy. Cancers (Basel). APMID: 37173921.

Chu J, Gao F, Yan M, Zhao S, Yan Z, Shi B, Liu Y. Natural killer cells: a promising immunotherapy for cancer. J Transl Med. 2022.

Meraz IM, et al. TUSC2 Immunogene Therapy Synergizes with Anti-PD-1 through Enhanced Proliferation and Infiltration of Natural Killer Cells in Syngeneic Kras-Mutant

Mouse Lung Cancer Models. Cancer Immunol Res. 2018

TUSC2 is important for cytotoxic NK cell optimal activation, which includes

proliferation and production of the killing molecules

Investigate the TUSC2-specific mechanisms of action on tumor immune cells

Modify the injection schedule of Quar Oze to achieve a prolonged effect of the nanoparticles

Combine nanoparticles with different immune checkpoint inhibitors to harness full function of cytotoxic cells

RNA-seq of cytotoxic immune cells under presence and absence of TUSC2

Run survival study to investigate durability of the response and to make sure that there is no recurrence.

Work with TUSC2 and NK only in vivo study in the mice model that Rag1-/- to

focus on NK only effect in a biological system.

Consider NK cell adoptive transfer after treatment with TUSC2 lipoparticles or

control

Training grant(T32)

Meharry Medical College Core Facilities, which are supported by NIH

Grants MD007586, CA163069, and S10RR025497".

Meharry Medical College Animal Care Facility.

Grant"Glycolytic Metabolism in TUSC2 Deficiency" provided by

Genprex, Inc

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Genprex Inc. published this content on April 19, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on April 19, 2026 at 22:11 UTC.