IF 14.1: Nanobiologics Targeting Splenic Myeloids Break PDAC Therapy Deadlock

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with a five-year overall survival below 7 %. High rates of local recurrence and distant metastasis after irreversible electroporation (IRE), together with limited efficacy of current immune-based therapies, constitute a long-standing clinical bottleneck. A study recently published in Advanced Science now offers a rational solution: nanobiologics that home to splenic myeloid cells and induce anti-tumour peripheral trained immunity, markedly improving IRE outcomes in pre-clinical PDAC models. Absin’s four-colour multiplex fluorescent IHC kit (abs50028) served as a key histo-phenotyping tool and is proud to have empowered this breakthrough.

I. Background: the “double bind” of PDAC therapy

Two major hurdles persist:

· Limited cytoreduction by IRE: although FDA-approved, IRE cannot eradicate all tumour cells, leading to rapid local recurrence;
· Immune-refractory TME: PDAC harbours an immunosuppressive microenvironment that blunts adaptive T-cell responses, while trained-immunity-based strategies remain largely unexplored.

The authors observed that PDAC progression remodels the splenic immune landscape—myeloid cells (monocytes/macrophages) expand while cytotoxic T and B cells drop. Targeting these splenic myeloid populations to induce tumouricidal trained immunity therefore emerged as a rational therapeutic angle.

II. Strategy: rational design of MDCa@RBC-Alipo nanobiologics

The team engineered a multimodal nanobiologic—MDCa@RBC-Alipo—with the following features:

1. Spleen-homing vector: hybrid vesicles composed of erythrocyte membrane (spleen-reticuloendothelial tropism) and apoA1-decorated liposomes for myeloid targeting;
2. pH-responsive cargo: CaCO₃ nanocores loaded with muramyl dipeptide (MDP), releasing MDP in acidified lysosomes to avoid systemic degradation;
3. Trained-immunity programming: MDP triggers epigenetic rewiring (H3K27ac, H3K4me3) of splenic myeloid cells, boosting TNF-α/IL-6 while suppressing IL-10, thereby generating a tumouricidal phenotype;
4. Therapeutic synergy: trained myeloid cells infiltrate residual tumours post-IRE, sensitising them to PD-L1 blockade and creating an “ablation + trained immunity + ICB” tri-modal regimen.

III. Key results: marked recurrence suppression and survival benefit

In subcutaneous and orthotopic PDAC mouse models MDCa@RBC-Alipo showed:

· Splenic immune rewiring: elevated CD11b⁺ myeloid fraction, reduced M2 macrophages, increased pro-inflammatory cytokines;
· Recurrence control: post-IRE residual tumour volume shrank >60 % compared with IRE-only controls;
· Survival extension: median survival reached 72 d versus 40 d in controls (80 % increase) with effective suppression of bloody ascites;
· Favourable safety: no weight loss or hepatorenal toxicity, no histopathological damage to major organs.

Immune-phenotyping by multiplex fluorescent IHC was central to validating these outcomes—enter abs50028.

IV. Powered by Absin: abs50028 for high-content immune profiling

To quantify infiltrating immune subsets (CD206⁺ M2 macrophages, CD8⁺ T cells, Foxp3⁺ Tregs, etc.) in spleen and tumour tissues, the authors used Absin’s four-colour multiplex fluorescent IHC kit (abs50028):

1. Need: simultaneous detection of multiple markers (CD3, CD8, CD206, Foxp3) with cellular resolution;
2. Merits of abs50028: high specificity, low background, compatible with high-resolution whole-slide imaging;
3. Quantitative read-outs:
  (1) 3-fold increase in intratumoural CD8⁺ T cells after MDCa@RBC-Alipo;
  (2) 40 % reduction in M2 macrophages (CD206⁺) and elevated M1/M2 ratio;
  (3) Decreased Foxp3⁺ Tregs when combined with αPD-L1.

V. Absin at a glance—more than reagents, your innovation partner

Beyond abs50028, Absin offers multiplex IHC kits spanning 2- to 10-plex and custom mIHC services, empowering researchers to map the tumour microenvironment with single-cell resolution.

Reference:

Wu S, Xu W, Shan X, et al. Targeting Splenic Myeloid Cells with Nanobiologics to Prevent Post-ablative Pancreatic Cancer Recurrence via Inducing Antitumor Peripheral Trained Immunity. Adv Sci. 2025;12(2413562). DOI: 10.1002/advs.202413562

Product used in the study:

Cat. #	Name	Size
abs50028	Four-colour multiplex fluorescent IHC kit (anti-rabbit)	20T/50T/100T

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