Global VISTA Inhibitor Clinical Trials & Market Opportunity Insight 2023 Report Highlights:
- Market Potential Of VISTA Inhibitors
- Market Commercialization Assessment Scenario
- Partnerships, Collaborations & Agreements
- Global VISTA Inhibitors Clinical Pipeline By Biomarker, Indication, Company, Country & Phase
- Global VISTA Inhibitors Market Dynamics
- Insight On 15 Companies Involved In Development Of VISTA Inhibiting Drugs
- Role Of VISTA As Inhibitory & Costimulatory Checkpoint
Download Report: https://www.kuickresearch.com/report-vista-inhibitors-vista-immune-checkpoint-vista-antibody-clinical-trial-vista-protein
Immune checkpoint molecules control the inhibitory and stimulatory pathways of the immune system to ensure equilibrium. They can stop immune responses before they become extreme and self-destructive, whereas stimulatory checkpoint molecules can signal for an attack against tumor or infected cells. To maintain tumor cell control, immune cells must invade the tumor microenvironment. However, immune – suppressive mechanisms that upregulate inhibitory pathways frequently cause their functions to be downregulated in the tumor microenvironment. By blocking the inhibitory checkpoint molecules, immune cells can be freed to multiply more rapidly and fight tumor cells. Given this information, immune checkpoint therapy is becoming a more popular method of treatment for a wider range of cancer types. While many novel immune checkpoint medicines are being investigated in clinical studies, the VISTA protein has emerged as another immune checkpoint that can be utilized for cancer immunotherapy in the recent years.
Mice studies have been used to identify V-domain Ig suppressor of T cell activation (VISTA), an extracellular inhibitory ligand of the Ig superfamily. Numerous alternative names for Vista include DD1, PD-1H, Dies1, among others. This gene is primarily expressed in hematopoietic tissues or tissues with a high infiltration of leukocytes in humans and encodes a 279-amino acid protein that bears 22% sequence identity to the PD-L1 ligand, a B7 family protein. High amounts of VISTA are produced by lymphocytes that invade tumors, including regulatory T cells and myeloid-derived suppressor cells. When VISTA is blocked by an antibody, tumor growth is slowed in animal models of melanoma and squamous cell carcinoma. When compared to uninfected people, monocytes from HIV-positive patients produce more VISTA. An increase in immunological activation and a decrease in CD4-positive T cells were connected with elevated VISTA levels.
It is difficult and controversial how VISTA affects immune regulation. VISTA functions as both a ligand that is expressed on antigen-presenting cells and a receptor on T cells. High levels of VISTA expression have been observed in a number of malignancies, including prostate, colorectal, and non-small cell lung cancer (NSCLC), its levels sometimes even exceeding PD-1 expression. However, further research is required to fully understand the immunoregulatory mechanism of VISTA in pancreatic cancer because different research investigations have reached conflicting conclusions.
Most preclinical data point to VISTA’s ability to inhibit the immune system. Anti – VISTA medicines are therefore encouraged as a method of enhancing the immune response against cancer cells. ImmuNext has been a front runner in the development of VISTA antibodies. The biotech company and the multinational giant Johnsons & Johnsons (JNJ) have partnered to develop JNJ-61610588, an anti-VISTA antibody. JNJ withdrew from the project claiming business reasons, but ImmuNext found a new partner in Curis, who is now in charge of overseeing the further development of the development, which has been rebranded as CI-8993. CI-8993 is a first-in-class VISTA antagonist that is presently undergoing phase I clinical testing. The company also entered into a strategic partnership with Roche to amplify the effects of VISTA in the treatment of inflammatory diseases.
Another antibody designed to limit the activities of the VISTA protein is SNS-101, produced by Sensei Biotherapeutics. Less than 50 clinical studies evaluating the efficiency of VISTA inhibitors in the treatment of cancer have been made public on the clinical trial database. The prospect of creating small molecule inhibitors to block several pathways at once was investigated in light of the homology between VISTA and B7 family proteins. In addition to its collaboration with ImmuNext, Curis is also creating CA-170, a proprietary first-in-class oral small molecule antagonist that targets PD-L1 and VISTA, both of which serve as inhibitors of immune activation.
In addition to this, pre-clinical studies are investigating the impact of VISTA inhibitors in combination with other immunotherapies have shown encouraging outcomes. In trials using CT26 colon cancer mice and B16 tumor-bearing mice, the treatment with anti – VISTA and anti – PDL1 antibodies resulted in tumor regression and improved survival in the mouse models. Another study to assess the combined effects of a VISTA mAb and TLR vaccination demonstrated tumor free survival in 50% of the mouse population carrying the B16 melanoma, in contrast to the partial effects reported when the mice were treated with the two treatments in monotherapy. Combination therapies are therefore necessary to give the drugs involved additional support, which can greatly boost the therapeutic effects of the treatment.
Additionally, research and development in this field has seen an increase in the development of new drugs that target this protein as a result of advancements in biotechnology and the use of computer-based molecular design. Using the company’s exclusive AI-directed Rational Antibody Discovery platform, Hummingbird Bioscience has created an IgG4 isotype anti-VISTA antibody that can bind with a location in the protein that was predicted using computational methods. This investigational drug exhibits good safety and efficacy characteristics and was able to enter clinical trials quickly in 2021 thanks to its rational design, which was mediated by the expected structure of its binding site. Phase I clinical studies for this drug are now being conducted for a number of solid cancer types.
At present, clinical activity and acceptable tolerability profiles have been shown for small compounds or mAb directed against VISTA. Nevertheless, the VISTA pathway’s relevance as a target for cancer immunotherapy is currently constrained by its complexity and a few uncertain molecular characteristics. Its applicability may be impacted by the fact that it is not equally expressed across all cancer types. In order to define its function within the immunological signatures of solid and hematological malignancies and to develop new treatment approaches, a deeper characterization of this immune checkpoint may be helpful.