Targeted Immune Modulation Strategies for Cancer, Infectious and Autoimmune Diseases

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: 31 July 2025 | Viewed by 5720

Special Issue Editors


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Guest Editor
West China School of Pharmacy, Sichuan University, Chengdu 610041, China
Interests: vaccine delivery; cancer vaccination; lymph-node targeting; immune tolerance induction; microneedle delivery system

E-Mail Website
Guest Editor
West China School of Pharmacy, Sichuan University, Chengdu 610041, China
Interests: targeted drug delivery; cell delivery, anti-metastasis therapy; polymer-drug conjugate

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute to our Special Issue entitled “Targeted Immune Modulation Strategies for Cancer, Infectious and Autoimmune Diseases”. The immune system plays a crucial role in the fight against infectious pathogens and cancerous cells, and its abnormal status may cause serious conditions such as cancer, infectious diseases and autoimmunity. Immune modulation could potentially treat these pathological conditions, and the precise targeting of the immune system, which includes lymphoid organs and immune cells, could enhance the efficacy and safety of therapy. In recent years, various microparticle-, nanoparticle- and cell-based delivery systems have been developed for targeted immune modulation, and the lymphoid targeting efficiency has been enhanced by optimizing their physico-chemical parameters such as size and surface charge, or by modifying their surface with targeting ligands. These optimized systems are designed to train and strengthen the immune system in order to eliminate harmful pathogens or cells, or to induce immune suppression or tolerance in order to reprogram the immune balance. The proper use of these immune modulation strategies could enhance the therapeutic or prophylactic efficacy of various immunotherapy.

This Special Issue aims to highlight recent advances in the application of immune modulation strategies that monitor the immune system against cancer, autoimmunity and infectious diseases. This Special Issue therefore presents innovative drug delivery and formulation strategies in the fields of vaccination, cancer immunotherapy and autoimmune monitoring.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

  • Novel vaccination and delivery strategies for stimulating humoral and cellular immune responses against various infectious diseases and cancer;
  • Immune monitoring strategies that aim to remold the abnormal immune conditions in autoimmune disease, such as immune suppression and immune tolerance induction;
  • The targeting of the cancer microenvironment or tumor-draining lymph nodes for stimulating anti-cancer immune responses.

We look forward to receiving your contributions.

Dr. Guangsheng Du
Dr. Lian Li
Guest Editors

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Keywords

  • immune modulation
  • lymphoid targeting
  • cancer immunotherapy
  • autoimmune disease
  • vaccine delivery

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Published Papers (4 papers)

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Research

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18 pages, 2224 KiB  
Article
HIFU-CCL19/21 Axis Enhances Dendritic Cell Vaccine Efficacy in the Tumor Microenvironment
by Bum-Seo Baek, Hyunmi Park, Ji-Woong Choi, Eun-Young Lee and Seung-Yong Seong
Pharmaceutics 2025, 17(1), 65; https://doi.org/10.3390/pharmaceutics17010065 - 6 Jan 2025
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Abstract
Background/Objectives: Effectively targeting treatment-resistant tumor cells, particularly cancer stem cells (CSCs) involved in tumor recurrence, remains a major challenge in immunotherapy. This study examines the potential of combining mechanical high-intensity focused ultrasound (M-HIFU) with dendritic cell (DC) vaccines to enhance immune responses against [...] Read more.
Background/Objectives: Effectively targeting treatment-resistant tumor cells, particularly cancer stem cells (CSCs) involved in tumor recurrence, remains a major challenge in immunotherapy. This study examines the potential of combining mechanical high-intensity focused ultrasound (M-HIFU) with dendritic cell (DC) vaccines to enhance immune responses against OLFM4-expressing tumors, a CSC marker linked to immune evasion and tumor growth. Methods: M-HIFU was applied to induce immunogenic cell death by mechanically disrupting tumor cells, releasing tumor-associated antigens and creating an immunostimulatory environment. DC vaccines loaded with OLFM4 were then administered to boost the immune response within this primed environment. Results: The combination of M-HIFU and DC vaccine significantly inhibited tumor growth and metastasis, with enhanced T-cell activation and increased recruitment of immune cells due to elevated chemokines CCL19 and CCL21. This synergy promoted immune memory, reducing the likelihood of recurrence. Conclusions: M-HIFU effectively promotes the migration of DC vaccines through CCL19/21, presenting a promising approach for cancer treatment. Further studies are recommended to optimize this combination for clinical applications, with potential to improve patient outcomes in challenging cancer types. Full article
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18 pages, 7233 KiB  
Article
The Intra-Articular Delivery of a Low-Dose Adeno-Associated Virus-IL-1 Receptor Antagonist Vector Alleviates the Progress of Arthritis in an Osteoarthritis Rat Model
by Shuang Luo, Hao Jiang, Qingwei Li, Shiping Yang, Xuemei Yu, Xiongliang Xu, Qing Xie, Xiao Ke and Qiang Zheng
Pharmaceutics 2024, 16(12), 1518; https://doi.org/10.3390/pharmaceutics16121518 - 25 Nov 2024
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Abstract
Background/Objectives: Interleukin-1 (IL-1) is a pivotal mediator in the pathological progression of osteoarthritis (OA), playing a central role in disease progression. However, the rapid clearance of IL-1 receptor antagonist (IL-1Ra) from the joints may hinder the efficacy of intra-articular IL-1Ra injections in reducing [...] Read more.
Background/Objectives: Interleukin-1 (IL-1) is a pivotal mediator in the pathological progression of osteoarthritis (OA), playing a central role in disease progression. However, the rapid clearance of IL-1 receptor antagonist (IL-1Ra) from the joints may hinder the efficacy of intra-articular IL-1Ra injections in reducing OA-associated pain or cartilage degradation. Methods: Sustaining sufficient levels of IL-1Ra within the joints via adeno-associated virus (AAV)-mediated gene therapy presents a promising therapeutic strategy for OA. In this study, we constructed an IL-1Ra expression cassette employing intron insertion in the coding sequence (CDS) region to enhance protein expression levels. Furthermore, we incorporated precisely targeted liver-specific microRNA (miRNA) sequences to specifically downregulate transgene expression within hepatic tissues, thereby ensuring more targeted and controlled regulation of gene expression. Results: A rat model of OA was employed to compare the efficacy of AAV5 and AAV9 for IL-1Ra delivery at both high and low doses. It was observed that low-dose, but not high-dose, AAV9-IL-1Ra resulted in a significant reduction in joint swelling, accompanied by a decrease in the diameter of the affected area and the preservation of biomarkers associated with trabecular bone integrity. Conclusions: These results highlight the great potential of AAV9-IL-1Ra in osteoarthritis therapy, with the promise of achieving long-term improvement through a single intra-articular injection. Full article
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Review

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30 pages, 7375 KiB  
Review
Subcellular Organelle Targeting as a Novel Approach to Combat Tumor Metastasis
by Zefan Liu, Yang Liu, Xin Kang, Lian Li and Yucheng Xiang
Pharmaceutics 2025, 17(2), 198; https://doi.org/10.3390/pharmaceutics17020198 - 5 Feb 2025
Viewed by 894
Abstract
Tumor metastasis, the spread of cancer cells from the primary site to distant organs, remains a formidable challenge in oncology. Central to this process is the involvement of subcellular organelles, which undergo significant functional and structural changes during metastasis. Targeting these specific organelles [...] Read more.
Tumor metastasis, the spread of cancer cells from the primary site to distant organs, remains a formidable challenge in oncology. Central to this process is the involvement of subcellular organelles, which undergo significant functional and structural changes during metastasis. Targeting these specific organelles offers a promising avenue for enhanced drug delivery and metastasis therapeutic efficacy. This precision increases the potency and reduces potential off-target effects. Moreover, by understanding the role of each organelle in metastasis, treatments can be designed to disrupt the metastatic process at multiple stages, from cell migration to the establishment of secondary tumors. This review delves deeply into tumor metastasis processes and their connection with subcellular organelles. In order to target these organelles, biomembranes, cell-penetrating peptides, localization signal peptides, aptamers, specific small molecules, and various other strategies have been developed. In this review, we will elucidate targeting delivery strategies for each subcellular organelle and look forward to prospects in this domain. Full article
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46 pages, 1455 KiB  
Review
Mannose and Lactobionic Acid in Nasal Vaccination: Enhancing Antigen Delivery via C-Type Lectin Receptors
by Mariana Colaço, Maria T. Cruz, Luís Pereira de Almeida and Olga Borges
Pharmaceutics 2024, 16(10), 1308; https://doi.org/10.3390/pharmaceutics16101308 - 8 Oct 2024
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Abstract
Background/Objectives: Nasal vaccines are a promising strategy for enhancing mucosal immune responses and preventing diseases at mucosal sites by stimulating the secretion of secretory IgA, which is crucial for early pathogen neutralization. However, designing effective nasal vaccines is challenging due to the complex [...] Read more.
Background/Objectives: Nasal vaccines are a promising strategy for enhancing mucosal immune responses and preventing diseases at mucosal sites by stimulating the secretion of secretory IgA, which is crucial for early pathogen neutralization. However, designing effective nasal vaccines is challenging due to the complex immunological mechanisms in the nasal mucosa, which must balance protection and tolerance against constant exposure to inhaled pathogens. The nasal route also presents unique formulation and delivery hurdles, such as the mucous layer hindering antigen penetration and immune cell access. Methods: This review focuses on cutting-edge approaches to enhance nasal vaccine delivery, particularly those targeting C-type lectin receptors (CLRs) like the mannose receptor and macrophage galactose-type lectin (MGL) receptor. It elucidates the roles of these receptors in antigen recognition and uptake by antigen-presenting cells (APCs), providing insights into optimizing vaccine delivery. Results: While a comprehensive examination of targeted glycoconjugate vaccine development is outside the scope of this study, we provide key examples of glycan-based ligands, such as lactobionic acid and mannose, which can selectively target CLRs in the nasal mucosa. Conclusions: With the rise of new viral infections, this review aims to facilitate the design of innovative vaccines and equip researchers, clinicians, and vaccine developers with the knowledge to enhance immune defenses against respiratory pathogens, ultimately protecting public health. Full article
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