MI2026 – Poster Presenters

The identification of novel and complex protein targets in drug discovery increasingly exposes the limitations of conventional antibody generation, particularly for targets that are poorly immunogenic or structurally challenging. These challenges can delay target validation and introduce risk into early-stage development. Ankyrons are engineered recombinant binding proteins (~15 kDa) designed to overcome these constraints, providing high-affinity, target-specific reagents in a rapid and scalable format.

Selected from ProImmune’s highly diverse TeraLibrary™ (~10¹² variants) using ribosome display, Ankyrons enable fully in vitro, high-throughput binder generation without the need for immunising animals. This allows accelerated targeting of difficult or novel antigens, including pathogen-derived proteins and emerging therapeutic targets, supporting faster progression from target identification to functional validation.

Their small size and robust biophysical properties offer advantages in tissue penetration and epitope accessibility. Ankyrons are readily deployable alongside antibodies across standard assay platforms including flow cytometry, immunofluorescence, Western Blot, ELISA immunohistochemistry and more. They can be engineered into multivalent or multispecific formats to support more complex assay designs and therapeutic hypotheses.

For drug developers, Ankyrons provide a flexible and cost-effective solution for de-risking early discovery by enabling precise epitope mapping, target engagement studies, and biomarker assay development. Their applicability across multiple species also supports translational studies and cross-species validation strategies.

Genetically engineered Salmonella strains are promising vectors for cancer therapy, but their clinical use is limited by host immune responses. A key immunogenic antigen, the phosphatase PhoN, is metabolically essential for bacterial survival in the vitamin B6-depleted tumour microenvironment and thus cannot be simply deleted. While conventional deimmunisation targets surface residues, we present a strategy of allosteric deimmunisation by mutating non-surface, buried residues within the dominant h2 helix T-cell epitope. We hypothesised that the epitope is allosterically coupled to the distal active site gate, allowing for the simultaneous modulation of immunogenicity and enzymatic function. Using a computational pipeline, we designed deimmunised variants and used molecular dynamics (MD) simulations to predict their functional effects. The simulations revealed that mutations in the h2 helix allosterically controlled the gate's flexibility. The enzymatic activities of the deimmunized variants were correlated with the MD predictions: two of the five designed variants exhibited 2~3-fold increases in catalytic function. This work demonstrates that non-surface epitopes can be rationally engineered to not only ablate immunogenicity but also to allosterically enhance protein function.

T cell receptor (TCR) cross-reactivity—the ability of one TCR to recognize multiple peptide–MHC (pMHC) complexes—is essential for immune adaptability but poses major safety risks for TCR-engineered cancer therapies, as molecular mimicry between tumor and self-peptides has led to severe off-target toxicities. We developed CROSSTCR, a comprehensive and manually curated database integrating experimentally validated evidence of TCR cross-reactivity. Bidirectional TCR–antigen relationships are annotated, and data reliability is ensured through rule-based filtering, expert curation, and multi-level verification using sequence alignment, ESM-2 embedding similarity, and structural comparison. The current release contains >20,000 TCR–pMHC interactions across ~1,500 cross-reactive groups. Despite low sequence similarity, peptides recognized by the same TCR share embedding proximity and convergent 3D conformations, revealing conserved features underlying cross-reactivity. A case study of the MAGE-A3/Titin mimicry event reproduced clinically observed off-target cardiotoxicity. The web platform provides interactive visualization and downloadable datasets. CROSSTCR offers the first systematic, validated resource for TCR cross-reactivity, supporting molecular mimicry assessment and safer design of TCR-based cancer immunotherapies.

Therapeutic monoclonal antibodies (mAbs) are widely used for treating diverse diseases, yet their clinical success is often hindered by polyreactivity caused by non-specific binding to off-target biomolecules. Early identification of polyreactivity risk is therefore essential to improve developability and reduce failure rates.We developed PolyXpert, a polyreactivity prediction model based on fine-tuned protein language models. Among six evaluated models, PolyXpert achieved the best performance, reaching an AUC of 0.9672 and ~90% accuracy on an independent test set.Our results show that fine-tuning PLMs significantly improves robustness compared to embedding-based approaches. PolyXpert provides an efficient in silico tool for early-stage screening and selection of therapeutic antibody candidates.Code is available at: https://github.com/zzyywww/PolyXpert

Occupational inhalation of respirable crystalline silica and coal dust is a fundamental cause of silicosis and coal workers' pneumoconiosis (CWP). However, the cellular mechanisms behind disease progression are not fully understood. Alveolar macrophages (AMs) are the main mediators of particulate clearance, but how sustained particle burden affects macrophage lipid metabolism and stress signalling remains poorly characterised. This study uses an integrated metabolic and transcriptomic approach in a murine model of occupational lung disease (OLD) to clarify these mechanisms.

Dust-exposed mice showed increased airway hyperresponsiveness and signs of emphysematous and fibrotic remodelling compared to controls (p < 0.05). Raman microspectroscopy identified co-localisation of intracellular silica with lipid-rich cellular regions, indicating neutral lipid accumulation. Transcriptomic analysis of silica-positive AMs showed strong enrichment of foam cell–associated gene signatures. There was upregulation of scavenger and lipid uptake receptors, such as CD36, and suppression of reverse cholesterol transporters (ABCA1, ABCG1). Genes involved in fatty acid transport and β-oxidation were downregulated, suggesting impaired lipid catabolism. These lipid metabolic disturbances were linked to activation of ER stress pathways, implying lipid overload contributes to proteostatic dysfunction. Silica-negative AMs showed intermediate transcriptional changes. Coal dust–exposed AMs exhibited overlapping yet distinct metabolic reprogramming. Cross-dataset validation confirmed progressive, foam cell–like transcriptional remodelling with increasing particle burden over time.

This study shows that particle-laden AMs exhibit coordinated lipid metabolic dysregulation, ER stress, and foam cell reprogramming. These are central processes in the pathogenesis of pneumoconiosis. Results suggest macrophage lipid homeostasis is a promising therapeutic target. Future research will define the temporal sequence of these events and test candidate interventions to slow early disease progression.

We investigated the mechanism by which eupalinolide B (EB) regulates DEK protein ubiquitination and degradation, and its impact on DEK-mediated receptor-interacting protein kinase 1 (RIPK)-PAN optosis pathway in allergic asthma.

In vitro, EB could bind to DEK. RNF149 and RNF170 were identified as regulatory factors of DEK, poly ubiquitinating the K349 site in the DEK coding DNA sequence region 270–350 through K48 linkages and leading to its degradation. RNA sequencing showed that DEK overexpression upregulated the expression of genes such as RIPK1, FADD, and Caspase 8. Treatment with DEK siRNA or EB reduced the activation of the RIPK1-PANoptosis pathway in BEAS-2B-DEK cells. In vivo, EB significantly reduced the levels of DEK in house dust mite-induced mice and alleviated pulmonary inflammatory cell infiltration, goblet cell hyperplasia, collagen fiber deposition, and eosinophil proportion in BALF. Knocking out the DEK gene reduced RIPK1-induced PANoptosis, and inhibited airway inflammation and cell apoptosis.

EB promotes the degradation of DEK by RNF149 and RNF170, inhibits the RIPK1-PANoptosis pathway, and may effectively suppress asthma. EB may become a potential drug for treating airway inflammation in asthma.

Suzhou 4a Biotechnology Co., Ltd., formerly known as Beijing 4a Biotechnology Co., Ltd., was founded in 2009. It is a national high-tech enterprise integrating biopharmaceutical product research and development, large-scale production, marketing, and professional technical services. After more than a decade of continuous development and technological accumulation, the company has built a complete technology platform with flow cytometry technology as its core feature, creating a rich product line covering immune detection, clinical diagnosis, and scientific research applications. Its business scope comprehensively covers three core areas: basic research in life sciences, innovative drug development, and in vitro diagnostics (IVD).

As a pioneer in the Chinese immunological research market, Suzhou 4a Biotechnology has established a long-term strategic partnership with ProImmune, a leading global provider of immunology solutions. For over two decades, the two companies have collaborated to deeply empower domestic research institutions, pharmaceutical companies, and clinical laboratories with professional products and high-quality services. Together, they are promoting the application of key technologies such as flow cytometry, antigen-specific T-cell analysis, and immune monitoring in the fields of oncology, vaccine development, infectious diseases, and autoimmune diseases, continuously injecting momentum into the high-quality development of China's life science and scientific research reagent industry.

Immunometabolic reprogramming is increasingly recognized as a driver of asthma pathogenesis, yet the molecular mechanisms linking lactate accumulation to airway inflammation via protein lactylation (Kla) remain elusive. In this study, we integrated a house dust mite (HDM)-induced asthma model with quantitative lactylomics to identify ATP6V1B2, a key V-ATPase subunit, as a core lactylation target. Combined molecular dynamics simulations and biochemical analyses revealed that intracellular L-lactate triggers lactylation at K108/K109. This modification restricts ATP6V1B2 conformational flexibility, leading to the disassembly of the V1-V0 complex and subsequent loss of proton pump activity. Crucially, the lactylation event was validated in primary human bronchial epithelial cells (HBEs), confirming that HDM and L-lactate stimulation induce ATP6V1B2 lactylation, thereby ensuring the clinical relevance of our findings. We demonstrate that this loss-of-function precipitates lysosomal alkalinization and membrane permeabilization (LMP). Crucially, LMP acts as a central node that bifurcates into two pathogenic cascades: it triggers a catastrophic mitochondrial ROS burst via Cathepsin B leakage. This oxidative burst functions as a pivotal redox signal that initiates a non-canonical Caspase-8/3/GSDME-dependent pyroptosis pathway, distinct from intrinsic apoptosis. In vivo, blocking ATP6V1B2 lactylation using an AAV-delivered lactylation-deficient (2 KR) mutant successfully severed this metabolic-inflammatory loop, significantly attenuating airway inflammation, Th2 cytokine release, and tissue pyroptosis. These findings characterize a novel 'L-lactate-ATP6V1B2-GSDME' axis, establishing ATP6V1B2 lactylation as a critical metabolic switch connecting lysosomal damage to inflammatory cell death, thereby identifying a potential therapeutic target for metabolic dysregulation in chronic asthma with severe pathology.

This study aimed to investigate the functional recovery of an 8-gene-edited pig heart after orthotopic xenotransplantation, the characteristics of the recipient’s immune responses, and the efficacy of postoperative complication management to provide comprehensive experimental evidence for the clinical translation of xenogeneic cardiac transplantation technology.

On December 27, 2025, an orthotopic heart was xenotransplanted from an 8-gene-edited pig to a rhesus macaque using the biatrial anastomosis technique. Postoperatively, comprehensive vital sign monitoring, immunosuppressive therapy, and complication interventions were implemented. Donor organ cardiac function, recipient immune indicators, and survival status were evaluated within 30 days after transplantation.

The recipient macaque survived for more than 30 days postoperatively. The cardiac function of the donor heart gradually stabilized, with the ejection fraction increasing from 58% in the early postoperative phase to 66%. No hyperacute immune rejection occurred. Postoperative complications, including infection, pleural effusion, and blood pressure fluctuations, were effectively controlled with symptomatic treatment.

An 8-gene-edited pig heart demonstrates good biocompatibility in xenogeneic cardiac transplantation. Standardized surgical procedures, precise immunosuppressive regimens, and comprehensive postoperative care can effectively ensure desirable transplantation outcomes. This study offers an important technical reference for clinical xenogeneic cardiac transplantation.