On November 3, 2026 Verismo Therapeutics, a clinical-stage CAR T cell therapy company pioneering a novel multi-chain KIR-CAR platform technology, reported new preclinical data demonstrating enhanced anti-tumor activity, reduced cytokine release, and lower T cell exhaustion with SynKIR-110 with reduced off-target activity compared to conventional single-chain CAR T designs. The data will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 41st Annual Meeting in Phoenix, Arizona (Abstract 253). The study evaluated SynKIR-110 against CD28- and 4-1BB-based single-chain CAR T cells in preclinical mesothelioma xenograft models.
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Poster Presentation Details
Title: Mesothelin-targeted Multi-Chain Killer Immunoglobulin Receptor (KIR)-based CAR T Reduces Exhaustion, Cytokine Release, and Enhances Safety Profile in vivo vs CD28 or 41BB single-chain CAR T
Presenter: Nora Yucel, Ph.D., Verismo Therapeutics
Session: Cellular Therapies — Chimeric Antigen Receptors
Session Date and Time: Friday, November 6, 2026 — 10 a.m.–2 p.m., 5–7 p.m. MT
Abstract Number: 253
Location: Phoenix Convention Center, Phoenix, Arizona
Full Abstract: View Source
In head-to-head comparisons, SynKIR-110 achieved the fastest tumor control among the three CAR T designs with low cytokine production, while CD28-based single-chain CAR T cells produced approximately 10-fold higher IFNγ and 30-fold higher TNFα and IL-2 levels. Tumor-infiltrating SynKIR-110 CD8 T cells also demonstrated reduced expression of exhaustion markers TIM3, LAG3, and PD1 compared to both single-chain comparators. Additionally, while both single-chain CAR T groups showed off-target activity in vitro and accumulation of CD8 CAR T cells in healthy lung tissue in vivo, no such effects were observed in SynKIR-110-treated animals.
"These preclinical head-to-head findings reinforce the mechanistic rationale behind the multi-chain KIR-CAR platform — that separating antigen binding from T cell activation can meaningfully reduce tonic signaling and non-specific off-target activity associated with conventional single-chain CAR T designs, without compromising antitumor control," said Laura Johnson, Ph.D., Chief Scientific Officer and Chief Operating Officer of Verismo Therapeutics. "Seeing SynKIR-110 deliver the fastest tumor control among the three CAR T architectures tested, with substantially lower cytokine production versus CD28-based single-chain CAR T, reduced T cell exhaustion markers compared with both single-chain comparators, and no off-target accumulation in healthy lung tissue, supports the differentiated safety and efficacy profile we are now evaluating in the ongoing STAR-101 clinical trial in patients with mesothelin-expressing solid tumors."
SynKIR-110 is currently being evaluated in the ongoing Phase 1 STAR-101 clinical trial (NCT05568680) in patients with advanced mesothelin-expressing solid tumors, including mesothelioma, ovarian cancer, and cholangiocarcinoma. Initial clinical data presented at AACR (Free AACR Whitepaper) 2026 showed a favorable safety profile in nine patients across the first three dose-escalation cohorts, with no dose-limiting toxicities, no Grade 3 or higher cytokine release syndrome, and no immune effector cell-associated neurotoxicity syndrome (ICANS) observed, while also demonstrating tumor reduction. SynKIR-110 has received Orphan Drug and Fast Track designations from the U.S. Food and Drug Administration for mesothelioma. Dose escalation remains ongoing to determine the recommended Phase 2 dose.
About the KIR-CAR Platform
The KIR-CAR platform is a multi-chain T cell therapy that has shown highly effective solid tumor treatment in otherwise CAR-resistant animal models with hard-to-treat tumors. Using NK cell-derived killer immunoglobulin-like receptor (KIR) and DAP12 to split the target binding and T cell activation signals provides a novel paired immune-receptor activation that is independent from CD3 signaling and does not require additional co-stimulation. KIR-CAR enables sustained cell receptor expression in T cells, and induces deeper, more durable tumor treatments. Together, this multi-chain cell signaling platform provides the potential to deliver effective patient treatments by minimizing the background activation and early T cell exhaustion observed in conventional single-chain CAR T therapy, with potential to treat patients with both solid and hematologic tumors.
(Press release, Verismo Therapeutics, NOV 3, 2026, View Source [SID1234674111])