Publications

Poster Presentation: Intratumoral Administration of Low Volume Ultra-High Concentration Nitric Oxide and Immune Checkpoint Inhibitors in CT26 Tumor-Bearing Mice

Dirbas, F. et al.

Poster Presentation: Intratumoral Administration of Low Volume Ultra High-Concentration Nitric Oxide andAnti-rPD-L1 Treatment Leads to Prolonged Survival in MAT B III Tumor-Bearing Rats

Pegram, M. et al.

Beyond Cancer Presents First-in-Class Clinical Data Showing an Immunogenic Response in Subjects with r/r Unresectable Solid Tumors Treated with Ultra-High Concentration Nitric Oxide (UNO)

ASCO

Poster Presentation: A Phase 1, Multi-center, Safety, Feasibility, and Preliminary Efficacy Study Evaluating a Single Dose of UNO101 in Relapsed or Refractory, Unresectable, Primary, or Metastatic Cutaneous and Subcutaneous Malignancies

Frederick M. Dirbas, et al.

Poster Presentation: Phase 1 Study of Ultra-High Concentration Nitric Oxide (UNO) in Relapsed or Refractory, Unresectable, Primary, or Metastatic Cutaneous and Subcutaneous Malignancies

Dirbas F., et al

Abstract: Phase 1 study of ultra-high concentration nitric oxide (UNO) in relapsed or refractory, unresectable, primary, or metastatic cutaneous and subcutaneous malignancies

Meirovitz A., et al

Manuscript: Gaseous nitric oxide tumor ablation induces an anti-tumor abscopal effect

Hila Confino et al

Poster: Ultra-High Concentration Nitric Oxide (UNO) Enhances Anti-CTLA-4 Treatment Activity and Induces a Durable Anti-Tumor Immune Response

Sela, Y. et al.

Poster: Intratumoral Administration of Ultra High-Concentration Nitric Oxide (UNO) and Anti PD-1Treatment Leads to High Tumor Regression Rates and Prolonged Survival in Tumor-Bearing Mice

Epshtein, Y. et al.

Abstract: Ultra-High Concentration Nitric Oxide (UNO) Enhances Anti-CTLA-4 Treatment Activity and Induces a Durable Anti-Tumor Immune Response

Sela Y. et al

Abstract: Intratumoral Administration of Ultra High-Concentration Nitric Oxide (UNO) and Anti PD-1 Treatment Leads to High Tumor Regression Rates and Prolonged Survival in Tumor-Bearing Mice

Epshtein Y. et al

Poster: Intratumoral Administration of Ultra High-Concentration Nitric Oxide (UNO) is more Efficacious than anti-mPD-1 Therapy in 4T1 Tumor-Bearing Mice

Confino H et al

Poster: Short-Term Exposure of Cancer Cells to Ultra-High Concentrations of Nitric Oxide (UNO) Activates the mPD-1/mPD-L1 Axis and Immune Responses

Confino H et al

Abstract: Short-Term Exposure of Cancer Cells to Ultra-High Concentrations Nitric Oxide Induces PDL-1 Upregulation

Confino H et al

Abstract: Intratumoral Administration of Ultra High-Concentration Nitric Oxide (UNO) is more Efficacious than Anti-PD1 Therapy in 4T1 Tumor-Bearing Mice

Confino H et al

Manuscript: Gaseous Nitric Oxide Tumor Ablation Induces an Anti-Tumor Abscopal Effect

Confino H et al

Poster Presentation: Intratumoral Administration of High-Concentration Nitric Oxide and Anti PD-1 Treatment Leads to Higher Tumor Regression Rates and Prolonged Survival in CT26 Tumor-Bearing Mice

Confino H et al

Poster: Intratumoral Administration of High-Concentration Nitric Oxide and Anti PD-1 Treatment Leads to Higher Tumor Regression Rates and Prolonged Survival in CT26 Tumor-Bearing Mice

Confino H et al

Abstract: Intratumoral Administration of High-Concentration Nitric Oxide and Anti PD-1 Treatment Leads to Higher Tumor Regression Rates and Prolonged Survival in CT26 Tumor-Bearing Mice

Confino H et al

Poster: Ultra-high concentrations of gaseous nitric oxide show rapid cytotoxic capabilities against colon, breast, pancreatic and other cancer cells in vitro.

Confino H et al

Poster: Single intra-tumoral injection of gaseous nitric oxide induces an adaptive immune response in a mouse CT-26 solid tumor model

Confino H et al

American Association for Cancer Research (AACR) Annual Meeting 2022

Confino H et al: Single intra-tumoral injection of gaseous nitric oxide induces an adaptive immune response in a mouse CT-26 solid tumor model

Conclusion: Intra-tumoral injection of ultra-high concentrations of NO at 20,000 and 50,000 ppm gNO led to increased recruitment of lymphocytes and T cells, B cells, macrophages and dendrocytes to the primary tumor. Increased T cells and B cells were detected in the spleen and blood 21 days post NO treatment. Decreased pMDSCs were detected in the spleen 21 days post NO treatment. The data suggest that gNOinduced innate and adaptive immune cell populations, and the reduction of immune suppressor cells, are indicative of an anti-tumor immune response that underlies the rejection of secondary tumors in gNO-treated mice.

American Association for Cancer Research (AACR) Annual Meeting 2022

Confino H et al: Ultra-high concentrations of gaseous nitric oxide show rapid cytotoxic capabilities against colon, breast, pancreatic and other cancer cells in vitro

Conclusion: Exposure of human ovarian and pancreatic cancer cell lines and mouse lung, melanoma, colon and breast cancer cell lines to 10,000 ppm –100,000 ppm gNOresulted in a dose dependent cytotoxic response. Higher concentrations lead to near instant cell death. Lower concentrations require a longer exposure period to elicit cell death. No viable cells were detected after exposure to 50,000 ppm gaseous NO for 1 minute. Together with the known ability of NO to activate and recruit the immune system, these results suggest that gNOmay be a potent therapeutic agent for tumor treatment across a range of tumor types.

American Association for Cancer Research (AACR) Conference on Tumor Immunology and Immunotherapy

Confino H et al: Nitric oxide tumor ablation stimulates an anti-tumor immune response in mice

2020 North American Conference on Lung Cancer

Confino H et al: Nitric oxide lung cancer active vaccination

Conclusion: Gaseous nitric oxide (gNO) treatment results in dose- and time-dependent inhibition of lung cancer cell proliferation and reduced viability in vitro. Treatment of primary LLC1 lung tumors in mice with gNO at a dose of 50,000 ppm for 10 minutes results in no uptake of a challenge tumor implanted up to 14 days later. No unanticipated mortality or signs indicating distress were noted in the animals. These preliminary data suggest that our innovative gNO-based treatment may treat lung tumors locally and their distant metastases systemically, potentially via stimulation of an anti-tumor immune response.

American Association for Cancer Research Virtual Annual Meeting II

Confino H et al: Gaseous nitric oxide at high concentration is a powerful anti-tumor agent both in-vitro and in-vivo

Conclusion: Our data demonstrate the potential utility of gaseous nitric oxide (gNO) as a treatment for cancer. In the current work, gNO at high concentrations showed a significant cytotoxic effect on cancer cells in vitro and in vivo. Moreover, our findings may indicate that tumor ablation with gNO stimulates an anti-tumor immune response.