Verismo reports new CAR T data on SynKIR-110
The multi-chain KIR-CAR therapy SynKIR™-110 achieved faster tumor control and lower cytokine production than conventional CAR T constructs in preclinical studies by Verismo Therapeutics. The company will present the data at the 41st annual meeting of the Society for Immunotherapy of Cancer.
- SynKIR™-110 showed the fastest tumor control of the three CAR T constructs evaluated.
- Compared with CD28-based CAR T, it produced approximately tenfold less IFNγ and 30-fold less TNFα and IL-2.
- Lower TIM3, LAG3 and PD1 expression was measured in tumor-infiltrating T cells.
- No off-target activity or accumulation in healthy lung tissue was observed with SynKIR™-110.
- The therapy’s Phase 1 STAR-101 clinical trial and dose escalation are ongoing.
Faster tumor control, lower cytokine production
Verismo Therapeutics, based in Philadelphia, said it compared SynKIR™-110 with CD28- and 4-1BB-based single-chain CAR T cells in mesothelioma xenograft models. Of the three constructs evaluated, SynKIR™-110 achieved the fastest tumor control.
Compared with CD28-based single-chain CAR T cells, SynKIR™-110 produced approximately tenfold lower levels of IFNγ and 30-fold lower levels of TNFα and IL-2. Cytokine release is an important consideration in the development of CAR T-cell therapies, but Verismo presents these results as preclinical data in its statement.
Fewer exhaustion markers and off-target activity
In tumor-infiltrating SynKIR™-110 CD8 T cells, expression of the exhaustion markers TIM3, LAG3 and PD1 was lower than with either of the two single-chain comparator constructs. In vitro studies showed reduced T-cell exhaustion, less off-target proliferation and lower toxicity, the company reported.
Researchers observed off-target activity in vitro in the single-chain CAR T groups, as well as accumulation of CD8 CAR T cells in healthy lung tissue in vivo. According to Verismo, neither phenomenon was observed in animals treated with SynKIR™-110.
Laura Johnson, Verismo’s chief scientific and operating officer, said the results support the idea that separating antigen binding from T-cell activation could reduce the tonic signaling and nonspecific, off-target activity associated with conventional single-chain CAR T constructs. According to the company’s statement, this was observed with SynKIR™-110 without compromising tumor control.
First clinical trial is underway
SynKIR™-110 is currently being evaluated in the Phase 1 STAR-101 clinical trial, identified by NCT05568680, in patients with advanced mesothelin-expressing solid tumors. The trial includes patients with mesothelioma, ovarian cancer and biliary tract cancer, among others.
According to the company, the initial clinical data presented at the AACR 2026 conference covered nine patients in the first three dose-escalation cohorts. No dose-limiting toxicities, Grade 3 or higher cytokine release syndrome, or immune effector cell-associated neurotoxicity syndrome were reported in these cohorts, while reductions in tumor size were also observed. Dose escalation is ongoing to determine the recommended Phase 2 dose.
SynKIR™-110 has received the U.S. Food and Drug Administration’s orphan drug and fast-track designations for the treatment of mesothelioma.
How the technology is designed
According to Verismo, the KIR-CAR platform is a multi-chain T-cell therapeutic approach. The system uses a killer immunoglobulin-like receptor, or KIR, derived from natural killer cells, together with DAP12 to separate target recognition from T-cell activation. The company says this paired immunoreceptor activation is independent of CD3 signaling and does not require additional costimulation.
According to Verismo’s statement, the platform is designed to support sustained T-cell receptor expression and reduce the background activation and early T-cell exhaustion observed with conventional single-chain CAR T therapies. The company says the technology may be applicable to both solid and hematologic cancers, but ongoing clinical trials of SynKIR™-110 will need to evaluate this further.
The data will be presented at the 2026 SITC meeting in Phoenix. The presentation is listed under abstract number 253 and will be delivered by Nora Yucel of Verismo.