What question did this study set out to answer?

The aim is to assess the safety and efficacy of LYC001, a novel IL-2 formulation, in enhancing antitumor immunity while minimizing side effects.

April 19, 2026

Abstract CT115: LYC001, a high-affinity hierarchical assembly for lymph node-targeted IL-2 immunotherapy: Preclinical validation of potent antitumor immunity and preliminary safety from the first-in-human phase Ia study

Key Points

The aim is to assess the safety and efficacy of LYC001, a novel IL-2 formulation, in enhancing antitumor immunity while minimizing side effects.
Utilized a high-affinity hierarchical assembly platform for IL-2 formulation.
Conducted preclinical studies in syngeneic murine tumor models to evaluate efficacy and immune activation.
Performed pharmacodynamic analysis in non-human primates to assess lymphocyte expansion and survival predictors.
Initiated Phase Ia clinical trial to determine safety, maximum tolerated dose, pharmacokinetics, and preliminary efficacy.
LYC001 demonstrated over 70% tumor growth inhibition in various murine tumor models.
Achieved a 10-fold increase in the CD8+ T cell to Treg ratio compared to control.
In non-human primates, LYC001 showed over 300% lymphocyte expansion, indicating strong immune response.
Phase Ia trial showed LYC001 was well-tolerated with no dose-limiting toxicities or vascular leak syndrome.

Abstract

Abstract High-dose systemic interleukin-2 (IL-2) has demonstrated efficacy in metastatic renal cell carcinoma and melanoma but is severely limited by vascular leak syndrome (VLS) and a short half-life. Current engineering strategies often compromise efficacy for safety. LYC001 is a novel IL-2 formulation engineered via a High-Affinity Hierarchical-Assembly Platform (H2P), utilizing PEG2000-DSPE to form a stable, non-covalent complex (Kd ≈ 10⁻⁸ M). Leveraging a hydrodynamic diameter of ∼15 nm, LYC001 is designed for preferential lymphatic uptake following subcutaneous (SC) administration. This "lymph-targeting" strategy, combined with a "masking effect, " aims to bias immune activation towards lymph-resident CD8+ T cells while minimizing systemic toxicity and Treg stimulation. In preclinical studies, LYC001 monotherapy demonstrated robust antitumor activity with tumor growth inhibition (TGI) rates 70% in multiple syngeneic murine tumor models (B16F10, CT26, Renca 300%, a historic predictor of survival benefit in IL-2 responders. LYC001 outperformed the marketed control, with 60% of high-dose (400, 000 IU/kg) subjects exceeding this efficacy threshold (mean increase 315%) compared to only 20% in the control group. Pharmacokinetics (PK) analysis in NHPs confirmed that SC administration of 200, 000 IU/kg LYC001 resulted in a longer T1/2 (5. 71 ± 0. 51 h vs 2. 27 ± 0. 54 h), higher Cmax (255 ± 60 IU/mL vs 123 ± 33 IU/mL), and greater AUC0-34h (1283 ± 209 h·IU/mL vs. 841 ± 322 h·IU/mL) compared to marketed products. By minimizing non-target tissue exposure, toxicology studies showed no evidence of VLS, cardiovascular toxicity, injection site reactions, or ADA, validating the safety of LYC001. LYC001-I-01 (CTR20254113) is an ongoing Phase Ia, open-label, single-center dose-escalation study in patients with advanced solid tumors, utilizing an accelerated titration followed by a 3+3 design (12, 000 IU/kg to 540, 000 IU/kg). Objectives are to evaluate safety, MTD determination, PK, immunogenicity, and preliminary efficacy. The first patient (12, 000 IU/kg) was successfully dosed and completed the DLT observation period. The drug was well-tolerated with no dose-limiting toxicities (DLTs) or signs of VLS. Enrollment is ongoing, and updated dose-escalation data will be presented. Citation Format: Shuhang Wang, Dongyan Liu, Yanjie Han, Mingzhen Li, Wenfeng Zeng, Wei Liang, Ning Li. LYC001, a high-affinity hierarchical assembly for lymph node-targeted IL-2 immunotherapy: Preclinical validation of potent antitumor immunity and preliminary safety from the first-in-human phase Ia 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 CT115.

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