【IF 14.1】Breaking Pancreatic Cancer Treatment Bottlenecks: How ANT BIO PTE. LTD. Empowers Nanobiologic-based Immunotherapy

Pancreatic cancer ranks among the most aggressive malignancies globally, with a 5-year survival rate below 7%. Two major hurdles have long hindered effective treatment: the high risk of recurrence and metastasis following local ablation therapies, and the limited responsiveness of pancreatic tumors to current immunotherapeutic strategies. A groundbreaking study recently published in Advanced Science (IF 14.1) addresses these challenges by introducing a novel approach: leveraging nanobiologics to target splenic myeloid cells and elicit antitumor peripheral trained immunity, thereby substantially improving treatment outcomes after irreversible electroporation (IRE) ablation. ANT BIO PTE. LTD. is proud to have supported this pivotal research, with its Absin brand four-color multiplex immunofluorescence staining kit (Cat. No.: abs50028) serving as a core experimental tool that enabled key findings.

Key Literature Information

1. Unmet Clinical Needs and Scientific Rationale

Pancreatic cancer’s therapeutic landscape is constrained by two critical limitations:

1.              Incomplete tumor elimination with local ablation: IRE, an FDA-approved minimally invasive technique for advanced pancreatic cancer, preserves critical adjacent structures like bile ducts and vasculature but often leaves behind residual tumor cells, which drive recurrence;

2.              Immunotherapeutic resistance: Most contemporary immunotherapies depend on activating T cells of the adaptive immune system. However, pancreatic cancer’s highly immunosuppressive tumor microenvironment (TME) severely compromises T cell function. In contrast, strategies harnessing the innate immune system’s "trained immunity"—a form of long-term functional reprogramming—have remained relatively unexplored for this disease.

A key discovery from the research team shed light on a potential solution: pancreatic cancer progression induces profound remodeling of the splenic immune compartment. Specifically, the study observed an increased proportion of myeloid cells (including monocytes and macrophages) in the spleen, accompanied by a reduction in B cells and cytotoxic T cells. These splenic myeloid cells subsequently migrate to the TME, where they amplify immunosuppression. This observation underscored the potential of targeting splenic myeloid cells and inducing trained immunity via epigenetic and metabolic reprogramming as a strategy to overcome pancreatic cancer’s therapeutic barriers.

2. Nanobiologic Design and Therapeutic Mechanism

To efficiently target splenic myeloid cells and trigger trained immunity, the research team engineered a multifunctional nanobiologic conjugate termed MDCa@RBC-Alipo. Its design integrates four key functional components:

1.              Dual-targeting delivery system: The nanobiologic combines red blood cell (RBC) membrane coating—exploiting the spleen’s natural clearance mechanism for damaged RBCs to achieve splenic tropism—with apolipoprotein A1 (apoA1)-modified liposomes. ApoA1 binds to specific receptors on myeloid cell surfaces, enhancing cell-type-specific targeting;

2.              pH-responsive drug release: Biocompatible CaCO₃ nanoparticles serve as a carrier for muramyl dipeptide (MDP), an immunomodulator. This formulation enables pH-sensitive release of MDP within the acidic environment of lysosomes, protecting the agent from degradation during systemic circulation;

3.              Trained immunity induction: Upon internalization by splenic myeloid cells, MDP upregulates epigenetic markers (H3K27Ac and H3K4me3), promoting the secretion of pro-inflammatory cytokines (TNF-α and IL-6) while suppressing the immunosuppressive cytokine IL-10. This reprograms myeloid cells into an antitumor phenotypic state;

4.              Combination therapy synergy: The induced trained immunity reverses the immunosuppressive TME of residual tumors following IRE, augmenting the efficacy of PD-L1 checkpoint inhibitors (aPD-L1). This forms a synergistic therapeutic paradigm: "ablation + immune training + immune checkpoint blockade."


Figure 1: Schematic illustrating the mechanism of MDCa@RBC-Alipo in inducing antitumor trained immunity

3. Preclinical Efficacy and Safety Outcomes

In both subcutaneous and orthotopic pancreatic cancer mouse models, MDCa@RBC-Alipo demonstrated robust therapeutic performance:

5.              Splenic immune reprogramming: Treatment significantly increased the proportion of CD11b⁺ myeloid cells in the spleen, reduced the number of pro-tumor M2-type macrophages, and enhanced the production of pro-inflammatory cytokines;

6.              Recurrence suppression: When combined with IRE, MDCa@RBC-Alipo reduced residual tumor volume by more than 60% compared to control groups, with a corresponding decrease in tumor weight;

7.              Survival extension: In orthotopic models, the combination of MDCa@RBC-Alipo and aPD-L1 achieved a median survival of 72 days—an 80% extension compared to the control group’s 40-day median survival—while effectively inhibiting hemoperitoneum formation;

8.              Favorable biosafety profile: The nanobiologic did not cause significant changes in mouse body weight or liver/kidney function, nor did it induce pathological damage to major organs (heart, liver, spleen, lungs, kidneys).

4. ANT BIO PTE. LTD. Product Support: The Critical Role of abs50028

Immune cell phenotyping was a cornerstone of validating the study’s hypotheses, and ANT BIO PTE. LTD.’s abs50028 four-color multiplex immunofluorescence staining kit was instrumental in this process:

9.              Experimental application: The kit enabled simultaneous detection of co-localization and expression levels of multiple immune cell markers (CD3, CD8, CD206, Foxp3), facilitating comprehensive evaluation of MDCa@RBC-Alipo’s effects on TME immune cell composition;

10.           Product capabilities: The abs50028 kit supports multi-target fluorescence labeling, distinguishing distinct antigens through dedicated fluorescence channels. Its high specificity minimizes non-specific staining, while its high sensitivity allows detection of low-abundance antigens—key features for high-resolution tissue section imaging;

11.           Data validation: Using the abs50028 kit, the research team obtained definitive evidence of immune modulation:

1.              A 3-fold increase in intratumoral CD8⁺ T cell infiltration in the MDCa@RBC-Alipo treatment group;

2.              A 40% reduction in CD206⁺ M2-type macrophages, accompanied by a significant elevation in the M1/M2 macrophage ratio;

3.              A marked decrease in Foxp3⁺ regulatory T cells (a key immunosuppressive cell population) when combined with aPD-L1.


Figure 4: Representative immunofluorescence images showing CD206 and CD3⁺ immune cell distribution in tumor tissues (Control vs. MDCa@RBC-Alipo Treatment Group) detected by ANT BIO PTE. LTD.’s abs50028 kit

5. About ANT BIO PTE. LTD.: More Than Reagents, A Partner in Innovation

ANT BIO PTE. LTD. is a leading provider of life science reagents, offering a comprehensive portfolio of antibodies, proteins, kits, and general reagents through three specialized sub-brands:

12.           Absin: Focuses on general reagents and kits (including multiplex immunofluorescence solutions);

13.           Starter: Specializes in high-quality antibodies;

14.           UA: Concentrates on recombinant proteins.

Beyond the abs50028 four-color kit utilized in this study, ANT BIO PTE. LTD. provides a full range of multiplex immunofluorescence solutions, including kits/services supporting up to 9-marker 10-color staining. Our commitment to delivering high-quality, cost-effective experimental tools empowers researchers worldwide to accelerate scientific discovery and translate insights into clinical progress.

Products Used in This Study

More Multiplex Immunofluorescence Kits

Reference

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

ANT BIO PTE. LTD. – Empowering Scientific Breakthroughs

At ANT BIO PTE. LTD., we are committed to advancing life science research through high-quality, reliable reagents and comprehensive solutions. Our specialized sub-brands (Absin, Starter, UA) cover a full spectrum of research needs, from general reagents and kits to antibodies and recombinant proteins. With a focus on innovation, quality, and customer-centricity, we strive to be your trusted partner in unlocking scientific mysteries and driving medical progress. Explore our product portfolio today and elevate your research to new heights.