Introduction

Since the discovery of VISTA (Wang et al., 2011) genOway has helped advancing scientific knowledge about this target by creating innovative and translatable humanized VISTA models.  The development of these models has led to successful Investigational New Drug (IND) applications.

The VISTA success story is an example of how genOway can help advance preclinical research due to our offer that provides ultimate predictability throughout the preclinical journey.

Would you like to discuss how we can support your research program?

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I) The role of genOway in unveiling the VISTA potential

Development of the  humanized VISTA model

Following the discovery of VISTA in 2011, genOway took on the challenge of developing the first humanized genO-hVISTA mouse model, despite the limited available information about this protein. Thanks to our 15 years of experience and the 2000+ models genOway had created on-demand at that time, we were able to develop two custom-made humanized VISTA mouse models. Tailoring our humanization strategy to clients' specific needs was essential for creating models that helped develop and test anti-VISTA therapies.

Learn more about our capabilities for generating custom-made models for ultimate predictability.

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genO-hVISTA and its contribution to scientific advances

Based on the experience with custom-made models, genOway created genO-hVISTA, a catalog model made accessible to the scientific community in 2017.

Pharmaceutical and biotech companies, as well as academic institutions, started to use the genO-hVISTA mouse model for their research, resulting in several scientific publications:

  • Identification of VISTA as a pH-selective ligand of PSGL-1 by Bristol-Myers Squibb, published in Nature in 2019 (Johnston et al., 2019). Read more
  • Researchers at ImmuNext and Dartmouth College found that VISTA is a regulator of T-cell activation, highlighting the importance of VISTA as a target for either agonists or antagonists (ElTanbouly et al., 2020, Science). Read more
  • Biodistribution and pharmacokinetics analysis of an anti-VISTA monoclonal antibody (Burvenich et al., 2024, EJNMMI). Read more

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II) From a promising target to innovative VISTA-based therapeutics

Kineta’s anti-VISTA antibody undergoing clinical trials

At the AACR conference in 2021, Kineta researchers presented the poster “A Fully Human anti-VISTA Antibody as a Promising Therapy Against Poorly Immunogenic Tumors.”

In this poster they used genO-hVISTA to show that Kineta's fully human anti-VISTA antibody, KVA12123, effectively blocks the immunosuppressive function of VISTA, thereby enhancing T-cell activation and promoting anti-tumor immune responses. This suggested that the KVA12123 antibody could be a promising therapeutic option for treating cancers that currently have limited treatment options due to their low immunogenicity.

Kineta announced in 2022 the FDA acceptance for investigational new drug (IND) for KVA12123 that is now in clinical trials.

▶️ Read Kineta’s research findings in Frontiers in Immunology here

 

Sensei Bio’s pH-selective anti-VISTA antibody IND approval

In 2022, Sensei Bio used genO-hVISTA and genO-BRGSF-HIS mouse models to develop and validate their pH-selective anti-VISTA antibody, SNS-101, which targets VISTA in acidic tumor microenvironments.

These models helped in assessing SNS-101's efficacy, safety and pharmacokinetic features, by minimizing cytokine release syndrome and avoiding rapid drug clearance.

This research, published in Nature Communications, supported the successful FDA approval of their pH-selective antibody for clinical trials in July 2023.‍

▶️ Check out Sensei Bio’s poster presented at SITC 2022 here

▶️ Read more on Sensei Bio’s research in Nature Communications here

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III) Accelerating the development of next-generation VISTA-targeting compounds

During the 2021 CURIS 1st VISTA Symposium, ~70% of pharma and biotech speakers, including Kineta Therapeutics, BMS, and ImmuNext, reported using genO-hVISTA, recognizing it as a standard in the field. As VISTA-related research extends to autoimmune conditions such as arthritis and inflammation, the need for reliable reference models becomes increasingly important.

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To increase the predictability of preclinical research, genOway has developed:‍

▶️ genO-hPD-1/hVISTA for efficacy assessment and profiling of immuno-oncology agents targeting human immune checkpoint PD-1 and/or VISTA

 

genOway is developing:

▶️ genO-hVISTA/hCD28 for efficacy assessment and profiling of immuno-oncology agents targeting human immune checkpoint CD28 and/or VISTA

▶️ genO-hVISTA/hFcγR for efficacy assessment of Fc-mediated effector function of anti-VISTA antibodies

▶️ genO-hVISTA/hFcγR/hSA/hFcRn for improved half-life and efficacy studies of Fc-mediated effector function of anti-VISTA antibodies

 

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genOway, your trusted partner for the development of innovative preclinical programs

Developing a new drug from a newly identified target can be a long journey. To make sure your research is heading the right direction, you need highly predictive preclinical tools. The VISTA success story shows the ability of genOway to create preclinical models that lead to scientific advances

Want to discuss how genOway can support your research program?

How to make innovative immunotherapies go clinical: the story of VISTA-targeted therapies

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