Thisted et al. developed SNS-101, a fully human antagonistic VISTA antibody that selectively binds to a unique epitope in protonated VISTA at low pH and mitigates the cytokine release syndrome associated with other non-pH-selective anti-VISTA antibodies. SNS-101 showed favorable pharmacokinetic and safety profiles in non-human primates. When combined with an anti-PD-1 inhibitor, SNS-101 demonstrated improved in vivo efficacy, modulated cytokine and chemokine signaling, and altered the tumor microenvironment in human VISTA knock-in MC38 colon, MB49 bladder, and MCA/1956 sarcoma syngeneic tumor models.
Contributed by Shishir Pant
ABSTRACT: VISTA, an inhibitory myeloid-T-cell checkpoint, holds promise as a target for cancer immunotherapy. However, its effective targeting has been impeded by issues such as rapid clearance and cytokine release syndrome observed with previous VISTA antibodies. Here we demonstrate that SNS-101, a newly developed pH-selective VISTA antibody, addresses these challenges. Structural and biochemical analyses confirmed the pH-selectivity and unique epitope targeted by SNS-101. These properties confer favorable pharmacokinetic and safety profiles on SNS-101. In syngeneic tumor models utilizing human VISTA knock-in mice, SNS-101 shows in vivo efficacy when combined with a PD-1 inhibitor, modulates cytokine and chemokine signaling, and alters the tumor microenvironment. In summary, SNS-101, currently in Phase I clinical trials, emerges as a promising therapeutic biologic for a wide range of patients whose cancer is refractory to current immunotherapy regimens.
Author Info: (1) Sensei Biotherapeutics Inc., 1405 Research Blvd, Suite 125, Rockville, MD, 20850, USA. (2) Sensei Biotherapeutics Inc., 1405 Research Blvd, Suite 125, Rockville, MD, 20850, USA
Author Info: (1) Sensei Biotherapeutics Inc., 1405 Research Blvd, Suite 125, Rockville, MD, 20850, USA. (2) Sensei Biotherapeutics Inc., 1405 Research Blvd, Suite 125, Rockville, MD, 20850, USA. (3) Sensei Biotherapeutics Inc., 1405 Research Blvd, Suite 125, Rockville, MD, 20850, USA. (4) Sensei Biotherapeutics Inc., 1405 Research Blvd, Suite 125, Rockville, MD, 20850, USA. (5) Sensei Biotherapeutics Inc., 1405 Research Blvd, Suite 125, Rockville, MD, 20850, USA. (6) Sensei Biotherapeutics Inc., 1405 Research Blvd, Suite 125, Rockville, MD, 20850, USA. (7) Sensei Biotherapeutics Inc., 1405 Research Blvd, Suite 125, Rockville, MD, 20850, USA. (8) Sensei Biotherapeutics Inc., 1405 Research Blvd, Suite 125, Rockville, MD, 20850, USA. (9) Sensei Biotherapeutics Inc., 1405 Research Blvd, Suite 125, Rockville, MD, 20850, USA. (10) Sensei Biotherapeutics Inc., 1405 Research Blvd, Suite 125, Rockville, MD, 20850, USA. (11) Sensei Biotherapeutics Inc., 1405 Research Blvd, Suite 125, Rockville, MD, 20850, USA. (12) Sensei Biotherapeutics Inc., 1405 Research Blvd, Suite 125, Rockville, MD, 20850, USA. (13) Sensei Biotherapeutics Inc., 1405 Research Blvd, Suite 125, Rockville, MD, 20850, USA. (14) genOway, Technopark Gerland, 69007, Lyon, France. (15) Department of Pathology and Immunology, Washington Univ. School of Medicine, Mailstop 8118, 425 South Euclid Ave, St. Louis, MO, 63110, USA. (16) genOway, Technopark Gerland, 69007, Lyon, France. (17) Department of Pathology and Immunology, Washington Univ. School of Medicine, Mailstop 8118, 425 South Euclid Ave, St. Louis, MO, 63110, USA. (18) Sensei Biotherapeutics Inc., 1405 Research Blvd, Suite 125, Rockville, MD, 20850, USA. evanderhorst@senseibio.com.
