Two nanobodies with the highest affinity for LILRB4 were identified through phage display library screening and used to construct nanobody-based dual epitope anti-LILRB4 STAR-T cells, which exhibit more potent tumor inhibition in vitro and in vivo than single epitope anti-LILRB4 STAR-T cells or dual epitope anti-LILRB4 CAR-T cells do...Single-cell RNA sequencing revealed that monocyte-mediated suppression of autologous T-cell function may be a primary mechanism underlying the failure of STAR-T therapy in nonresponders. In conclusion, this first-in-human trial demonstrates the therapeutic potential of targeting LILRB4 with STAR-T-cell therapy in AML and warrants further investigation.

P=N/A, N=1, Completed, Institute of Hematology & Blood Diseases Hospital, China | Not yet recruiting --> Completed | N=10 --> 1

Herein, we present the phase 1a dose escalation data of IO-202 as monotherapy and in combination with azacitidine (AZA) in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) and R/R chronic myelomonocytic leukemia (CMML), and the phase 1b dose expansion data of IO-202 combined with AZA for the treatment of hypomethylating agent (HMA)-naïve CMML. Overall, the data support a future pivotal study of IO-202 + AZA in patients with HMA-naïve CMML. This trial was registered at www.clinicaltrials.gov as #NCT04372433.

P1, N=12, Recruiting, Institute of Hematology & Blood Diseases Hospital, China | Not yet recruiting --> Recruiting

P1, N=222, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

P1, N=11, Completed, Peking University People's Hospital | Trial primary completion date: Dec 2023 --> Aug 2024 | Not yet recruiting --> Completed

P1, N=67, Completed, Immune-Onc Therapeutics | Active, not recruiting --> Completed | N=106 --> 67 | Trial completion date: Jan 2027 --> Jan 2025 | Trial primary completion date: Jan 2026 --> Jan 2025

P1, N=230, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Feb 2025 --> Jun 2025 | Trial primary completion date: Feb 2025 --> Jun 2025

P1, N=130, Active, not recruiting, NGM Biopharmaceuticals, Inc | Recruiting --> Active, not recruiting

P1, N=280, Recruiting, Biond Biologics | Not yet recruiting --> Recruiting

P1, N=106, Active, not recruiting, Immune-Onc Therapeutics | Recruiting --> Active, not recruiting

P1, N=22, Completed, Immune-Onc Therapeutics | Active, not recruiting --> Completed | N=200 --> 22