KVA12123: A Promising New Anti-VISTA Antibody for Cancer Immunotherapy

A recent study published in Frontiers in Immunology has shed light on a promising new immune checkpoint inhibitor, KVA12123, developed by Kineta Inc. This fully human monoclonal antibody targets VISTA (V-domain Ig suppressor of T cell activation), a key driver of immunosuppression in the tumor microenvironment.

VISTA is primarily expressed on myeloid cells and plays a crucial role in maintaining immune tolerance. However, in cancer, VISTA allows tumors to evade an effective immune response. By blocking VISTA, KVA12123 has demonstrated the ability to restore an efficient antitumor immune response in preclinical models.

One of the unique features of KVA12123 is its high affinity binding to a distinct epitope on VISTA, different from other clinical-stage anti-VISTA antibodies. This binding specificity enables KVA12123 to effectively block VISTA's interaction with its binding partners, such as VSIG3, VSIG8, PSGL1, and LRIG1, at both neutral and acidic pH levels found in the tumor microenvironment.

In vitro studies showed that KVA12123 enhances T-cell activation, induces monocyte activation, and reverses VISTA-mediated suppression of activated T-cells. Notably, the antibody demonstrated strong single-agent antitumor activity in several syngeneic tumor models and enhanced efficacy when combined with anti-PD-1 treatment.

To improve its pharmacokinetic characteristics and reduce Fc-effector functions, KVA12123 was engineered with a YTE mutation. This modification resulted in a well-tolerated safety profile in preclinical toxicology studies, with no indicators of toxicity or cytokine release syndrome.

ichorbio, a leading provider of high-quality antibodies for in vivo research, offers a range of products that have contributed to the success of this study. For example, the anti-mouse PD-1 antibody (clone RMP1-14, product code ICH1132) used in combination with KVA12123 in the syngeneic tumor models is available through ichorbio. Additionally, the anti-mouse CTLA-4 (clone 9D9, product code ICH1096) and anti-mouse PD-L1 (clone 10F.9G2, product code ICH1086) antibodies used in the proof-of-concept experiments are also part of ichorbio's extensive catalog.

The findings of this study establish KVA12123 as a promising drug candidate with a distinct mechanism of action complementary to first-generation immune checkpoint inhibitors. The antibody is currently being evaluated in a Phase 1/2 open-label clinical trial, both as a monotherapy and in combination with pembrolizumab, in patients with advanced solid tumors.

As we eagerly await the results of the ongoing clinical trial, it is clear that KVA12123 has the potential to become a valuable addition to the growing arsenal of cancer immunotherapies. With its unique binding properties, favorable safety profile, and synergistic effects with other checkpoint inhibitors, this anti-VISTA antibody may soon offer new hope for patients battling difficult-to-treat cancers.