Abstract Background: While protein-based T cell engagers (TCEs) show promise for hematologic malignancies, challenges remain in safety, efficacy, and durability. ABO2203 provides a novel strategy as a first-in-class, lipid nanoparticle (LNP) -encapsulated messenger RNA (mRNA) encoding a CD3×CD19 TCE. This approach not only proved superior in preclinical studies, but also demonstrated more favorable pharmacokinetics, improved safety, and enhanced anti-tumor potency. Methods: This trial (NCT07072169) enrolled patients with relapsed/refractory CD19+ B cell non-Hodgkin lymphoma (B-NHL) who had received at least 2 prior lines of therapies for diffuse large B-cell lymphoma (DLBCL) or at least one for other subtypes, with no available standard care options. Dose escalation followed a modified 3+3 design across three cohorts: 3-480 µg, 120-960 µg, and 240-1920 µg. Treatment was administered subcutaneously on a weekly basis; upon achieving a complete response, the dosing interval could be extended. The primary endpoints were adverse events and dose-limiting toxicities (DLTs). Secondary endpoints included pharmacokinetics, pharmacodynamics, and efficacy as assessed per the Lugano 2014 criteria. Results: As of November 28, 2025, enrollment of the dose escalation phase completed, including three follicular lymphoma, two DLBCL, two marginal zone lymphoma, and two mantle cell lymphoma patients. No DLTs, serious treatment-emergent AEs (TEAEs), or TEAEs leading to treatment discontinuation were reported. TEAEs occurred in all patients. The most common TEAEs included pyrexia (seven 78%), interleukin level increased (six 67%), and neutrophil count decreased (four 44%). Grade 3-4 TEAEs observed in three (33%) patients, including one patient with concurrent grade 3 decreases in white blood cell (WBC) and neutrophil count, one with grade 3 WBC decreased and grade 4 neutrophil count decreased, and one with grade 3 blood fibrinogen decreased, all of which resolved without sequelae. Seven patients had completed at least one post-treatment tumor assessment, with two cases awaiting assessment. Among seven efficacy-evaluable patients, the objective response rate was 43% (3/7) and the disease control rate was 71% (5/7), including two (29%) complete metabolic responses. ABO2203-encoded TCE exhibited dose-dependent exposure, with a median time to maximum concentration of 5. 5 days after each dose and a mean terminal half-life of 7. 9 days. Moreover, LNP component had a short half-life (mean 2. 4 days), indicative of minimal accumulation risk. Conclusion: ABO2203 achieved initial clinical proof-of-concept. Its LNP-mRNA platform showed a well-tolerated safety profile and dose-dependent anti-tumor activity in heavily pretreated B-NHL patients, supporting its continual development in B-NHL. Citation Format: Li Wang, Rong Shen, Muchen Zhang, Bo Ying, Wenjie Song, Yan Wu, Shiping Ma, Peng Gao, Xinpeng Ma, Jerry Zhang, Lingyin Zhu, Rui Lin, Weili Zhao. ABO2203, a messenger RNA encoding a CD3×CD19 T cell engager, for relapsed/refractory B cell non-Hodgkin lymphoma: Preliminary results from first-in-human study abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (8Suppl): Abstract nr CT032.
Wang et al. (Fri,) studied this question.
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