Recently, the first-in-human clinical research paper regarding dual-epitope anti-LILRB4 STAR‑T for relapsed/refractory acute myeloid leukemia (R/R AML), jointly completed by BristarImmunotech, Peking University People’s Hospital and School of Basic Medical Sciences, Tsinghua University, has been formally accepted for publication by Signal Transduction and Targeted Therapy (IF=52.7). Backed by proprietary STAR‑T technology platform and self-developed dual-epitope nanobody targeting LILRB4, this pioneering first-in-human exploratory clinical data has verified the clinical feasibility and therapeutic potential of the candidate, providing critical references for subsequent preclinical translation and clinical development of LILRB4-targeted and STAR-T-based therapies for R/R AML.

Technological Innovation: Building a Differentiated Therapeutic System for AML Treatment

The novel therapy is built on three core innovations: proprietary STAR‑T platform, dual-epitope nanobody engineering and LILRB4-specific targeting, forming a differentiated technical route distinct from conventional CAR-T for AML treatment and laying a solid foundation for subsequent clinical advancement:

• Precision Targeting: LILRB4 is highly enriched on blasts and leukemic stem cells of M4/M5-subtype AML while barely expressed on normal hematopoietic stem cells, rendering it an ideal candidate therapeutic target for monocytic AML with favorable targeting selectivity.
• Dual-Epitope Nanobody Design: Two high-affinity nanobodies binding disparate epitopes of LILRB4 were identified via phage screening; the dual-epitope STAR-T construct strengthens antigen recognition capacity and lowers the risk of tumor escape driven by target antigen mutation.
• Unique Advantages of STAR-T Platform: As a proprietary Synthetic T Cell Receptor and Antigen Receptor (STAR), STAR-T inherits the antigen-binding feature of CAR and intact natural TCR intracellular signaling cascade. Characterized by low constitutive tonic signaling and superior antigen sensitivity, STAR-T can robustly activate T cells even against tumors with low target antigen expression, demonstrating distinctive edges over CAR-T in signal transduction and effector regulation.

In parallel, BristarImmunotech is advancing site-specific integration-based universal STAR-T pipeline enabled by CRISPR gene editing and AAV integration technology. The platform is expected to shorten production cycle and mitigate GvHD risks to improve patient accessibility. The company’s CD19-targeted universal STAR-T research findings have been published in Nature Medicine, corroborating the platform’s academic value.

Early Clinical Exploration: Preliminary Safety and Efficacy Findings

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy, with M4/M5 monocytic subtype associated with dismal prognosis and high post-standard-treatment relapse rate. Conventional CAR-T is largely hampered in AML development due to non-selective target expression and on-target/off-tumor toxicity against normal hematopoietic stem cells.

The enrolled cohort consisted of 9 LILRB-positive R/R AML patients all diagnosed with FAB M4/M5 subtype, among whom 77.8% had suffered disease relapse post allogeneic hematopoietic stem cell transplantation (allo-HSCT); six subjects completed full safety and efficacy assessment:

• Manageable Safety Profile: No Grade ≥3 cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) was observed; 83.3% of patients only developed Grade 1–2 manageable CRS, and no overt off-target injury to normal hematopoietic stem cells was detected.
• Promising Clinical Activity: The best overall response rate (ORR) stood at 50.0% among evaluable subjects. Two responding patients achieved sustained minimal residual disease (MRD)-negative complete remission (CR) for over 16 months after bridging allo-HSCT. Robust in vivo expansion of STAR-T cells was detected, accompanied by marked reduction of LILRB4-positive leukemic blasts.
• Elucidation of Treatment Failure Mechanism: Single-cell RNA sequencing unveiled that monocyte-derived autologous T-cell suppression constitutes the primary driver of therapeutic non-response, paving rational directions for future protocol optimization.

Milestone Progress: From Bench Innovation to Early Clinical Validation

YTS104 (LILRB4 STAR‑T) has fulfilled a full R&D milestone chain: granted FDA Orphan Drug Designation in December 2022; preclinical data unveiled at 2023 AACR Annual Meeting; obtained China NMPA IND approval on January 23, 2024; preliminary IIT clinical outcomes released at 2024 ASH Annual Meeting; first-in-human study formally published in 2026, closing the full-loop from fundamental research to early clinical exploration.

As the world’s first prospective human trial for LILRB4-directed STAR-T against R/R AML, this research preliminarily proves the modality’s clinical feasibility and therapeutic prospect, bringing a novel investigational option for heavily pretreated patients with post-transplant recurrent AML and supporting further development of combination regimens and universal STAR-T candidates.

Prof. Xin Lin, Scientific Founder of BristarImmunotech, commented: “The published research validates the unique R&D value of proprietary STAR-T platform in developing novel hematological malignancy targets. This early clinical exploration opens up new avenues for AML immunotherapy. Going forward, our team will continuously optimize therapeutic protocols and launch larger-scale clinical trials to translate homegrown innovative cellular therapies to benefit global patients.”

Contact Us

•Email: info@bristarimmunotech.com

•BD Cooperation: jinming@bristarimmunotech.com

•Clinical Cooperation: zhenghongli@bristarimmunotech.com