Verismo's Novel KIR-CAR Platform Shows Superior Tumor Control with Reduced Toxicity in Preclinical Studies
核心洞察
Verismo Therapeutics (搜索) presented preclinical data at ASH 2025 showing SynKIR™-310 achieved faster and deeper tumor control compared to conventional CD19 (搜索) CAR-T therapies like tisagenlecleucel.
The novel KIR (搜索)-CAR signaling platform demonstrated superior anti-tumor activity while producing substantially lower levels of inflammatory cytokines in mouse models.
SynKIR™-310 is currently being evaluated in a Phase 1 clinical trial for patients with relapsed/refractory B-cell non-Hodgkin lymphoma, including those previously treated with CD19 (搜索) CAR-T therapies.
Verismo Therapeutics (搜索) presented compelling preclinical data at the American Society of Hematology (ASH) Annual Meeting 2025, demonstrating that its novel SynKIR™-310 KIR (搜索)-CAR T cell therapy achieved superior tumor control with reduced cytokine production compared to conventional CD19 (搜索)-targeting CAR-T therapies. The findings suggest potential for improved efficacy and safety in treating B-cell malignancies.
Enhanced Tumor Control at Lower Doses
In immunocompromised NSG mice with high B cell tumor (NALM6) burden, low doses of SynKIR™-310 demonstrated faster tumor elimination compared to tisagenlecleucel analog FMC63-41BBζ CAR T, which showed significantly lower anti-tumor activity. Dr. Megan Blair, Scientist at Verismo Therapeutics (搜索), presented the data in a poster titled "SynKIR™-310 Split-Signaling Based KIR (搜索)-CAR T Cell Therapy Achieves Faster and Deeper Anti-B Cell Tumor Efficacy with Reduced Cytokine Levels."
The superior performance was attributed specifically to the KIR (搜索)-CAR signaling mechanism rather than the CD19 (搜索)-targeting component. Direct comparisons between SynKIR™-310 (DS191-KIR-CAR), FMC63-KIR-CAR, and FMC63-41BBζ CAR T cells confirmed that KIR-CAR signaling was responsible for the enhanced tumor control versus conventional CAR-T approaches.
Reduced Cytokine Production Addresses Safety Concerns
A critical finding was SynKIR™-310's ability to achieve deeper tumor control while producing substantially lower levels of inflammatory cytokines. In the NALM6 mouse model, SynKIR™-310 T cells generated significantly reduced levels of IFNγ, TNFα, and IL-2 cytokines compared to FMC63-41BBζ CAR T cells.
"Current approved CD19 (搜索) CAR T therapies have transformed treatment for patients with B-cell cancers, although many still experience some toxicity from cytokine release syndrome. Even with this therapy, about half of patients have disease progression within a year, at least in part attributed to early T cell exhaustion or loss of function," said Dr. Laura Johnson, CSO/COO of Verismo Therapeutics (搜索).
Clinical Development and Platform Technology
SynKIR™-310 is currently being evaluated in a Phase 1 clinical trial (NCT06544265) for patients with relapsed/refractory B-cell non-Hodgkin lymphoma, including those who have previously received CD19 (搜索) CAR-T therapies. The therapy leverages Verismo's KIR (搜索)-CAR split-signaling platform, designed to preserve T cell functionality and reduce exhaustion compared to conventional single-chain CAR-T constructs.
The KIR (搜索)-CAR platform represents a multi-chain CAR-T cell therapy using NK cell-derived KIR and DAP12 (搜索) split-signaling that provides novel paired activation independent from CD3 signaling and does not require 41BB/CD28 co-stimulation. This design enables sustained chimeric receptor expression with improved long-term CAR-T cell function and decreased T cell exhaustion.
Addressing Unmet Medical Needs
Verismo Therapeutics (搜索), a subsidiary of HLB Innovation (搜索), is the only company developing the KIR (搜索)-CAR platform. The company has two assets in Phase 1 clinical trials: SynKIR™-110 (NCT05568680) and SynKIR™-310 (NCT06544265). The platform technology was developed specifically to address areas of high unmet medical need, including advanced solid tumors and B cell-associated disorders and malignancies.
"These new data suggest that SynKIR™-310's novel KIR (搜索)-CAR signaling design may promote earlier tumor control that is stronger and more durable, with potentially reduced risk of cytokine-induced toxicity, supporting its ongoing clinical evaluation in patients with relapsed or refractory B cell leukemias or lymphomas," Johnson added.
The KIR (搜索)-CAR platform has demonstrated highly effective prolonged solid tumor treatment in otherwise CAR-resistant preclinical animal models with challenging tumor microenvironments, resulting in CAR-T cell resistance to tumor immunosuppression, prolonged functional persistence, and improved tumor elimination.