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Pharmaceutics
Special Issues
Targeted Immune Modulation Strategies for Cancer, Infectious and Autoimmune Diseases
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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: closed (30 April 2026) | Viewed by 22727

Editors

Dr. Guangsheng Du

E-Mail Website
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
Special Issues, Collections and Topics in MDPI journals
Dr. Lian Li

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

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

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

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Published Papers (7 papers)

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Research

Jump to: Review

40 pages, 24796 KB  
Article
AZD4635 Targets cAMP/CREB Axis to Salvage PARPi-Induced Immune Evasion and Enhance Antitumor Efficacy in Ovarian Cancer
by Botao Pan, Xiujuan Yang, Xuanji Wang, Jiahao Fang, Qingqing Liu, Ning Zou, Chenglai Xia and Huiling Shang
Pharmaceutics 2026, 18(2), 257; https://doi.org/10.3390/pharmaceutics18020257 - 19 Feb 2026
Viewed by 982
Abstract
Background/Objectives: Poly(ADP-ribose) polymerase inhibitors (PARPis) have significantly transformed the treatment landscape for ovarian cancer; however, their clinical efficacy is often limited by poor response rates and the emergence of resistance. Recent studies have revealed that in ovarian cancer cells resistant to PARPi, [...] Read more.
Background/Objectives: Poly(ADP-ribose) polymerase inhibitors (PARPis) have significantly transformed the treatment landscape for ovarian cancer; however, their clinical efficacy is often limited by poor response rates and the emergence of resistance. Recent studies have revealed that in ovarian cancer cells resistant to PARPi, the expression levels of adenosine receptors are upregulated. Accumulation of adenosine activates adenosine A2A receptor (A2AR) on immune cells, leading to immune suppression and immune escape. We hypothesize that this is a key factor limiting the efficacy of PARPi and driving the development of resistance. Therefore, the rational combination of PARPi with A2AR antagonists (A2ARas) may represent a highly promising anticancer strategy. Methods: To assess the effects of the PARPi AG14361 and the A2ARa AZD4635 on ovarian cancer growth and the immune microenvironment, we conducted in vitro and in vivo experiments and utilized single-cell RNA sequencing (scRNA-seq) to construct a high-resolution immune landscape. Results: AG14361 significantly inhibited ovarian cancer growth both in vitro and in vivo, accompanied by the accumulation of cyclic adenosine monophosphate (cAMP) and activation of the cAMP/cAMP response element-binding protein (CREB) pathway in mouse cells and tumor tissues. However, compared to monotherapy, the combination of AG14361 and AZD4635 significantly enhanced antitumor activity by inhibiting cAMP accumulation and the cAMP/CREB pathway. More importantly, the combination therapy of PARPi and A2ARa reduced the infiltration of immunosuppressive cells (such as regulatory T cells and M2 macrophages) while increasing the infiltration of cytotoxic T cells and granzyme B-positive cells, thereby creating a more favorable immune microenvironment for tumor clearance. Single-cell analysis revealed distinct functional subpopulations of macrophages and T cells, highlighting the complexity of immune heterogeneity and the potential for targeting specific immune cell subpopulations to enhance therapeutic efficacy. Conclusions: These findings suggest that the combination therapy of PARPi and A2ARa is a highly promising strategy that overcomes PARPi-induced immune escape by targeting the cAMP/CREB axis, thereby synergistically enhancing antitumor effects and holding promise as an effective treatment for solid tumors. Full article
(This article belongs to the Special Issue Targeted Immune Modulation Strategies for Cancer, Infectious and Autoimmune Diseases)
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18 pages, 2224 KB  
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
Cited by 3 | Viewed by 3236
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
(This article belongs to the Special Issue Targeted Immune Modulation Strategies for Cancer, Infectious and Autoimmune Diseases)
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18 pages, 7233 KB  
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
Cited by 5 | Viewed by 3293
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
(This article belongs to the Special Issue Targeted Immune Modulation Strategies for Cancer, Infectious and Autoimmune Diseases)
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Review

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30 pages, 1916 KB  
Review
Ambivalent Copper: Mechanistically Distinct Immune Effects Driving Innovation in Cancer Nanomedicine
by Devon Heroux, Xu Xin Sun, Zeynab Nosrati and Marcel B. Bally
Pharmaceutics 2026, 18(1), 75; https://doi.org/10.3390/pharmaceutics18010075 - 7 Jan 2026
Cited by 2 | Viewed by 1700
Abstract
Copper (Cu) is an essential element required by all living cells, where it supports critical enzymatic and signaling functions. In cancer, this balance is often disrupted, creating vulnerabilities that can be therapeutically exploited. Changes in Cu availability have been shown to influence key [...] Read more.
Copper (Cu) is an essential element required by all living cells, where it supports critical enzymatic and signaling functions. In cancer, this balance is often disrupted, creating vulnerabilities that can be therapeutically exploited. Changes in Cu availability have been shown to influence key immunoregulatory pathways, including those involved in inflammation, cell death, and immune evasion. Notably, Cu can drive expression of programmed death ligand 1 (PD-L1), contributing to immunosuppression, while also promoting immunogenic cell death, which stimulates adaptive immune responses. These dual effects highlight the complexity and therapeutic potential of Cu-based interventions, particularly in the context of immune modulation and toxicity. This review argues that Cu-based nanomedicines can selectively deliver high concentrations of bioactive Cu to tumor cells, inducing cell death and triggering adaptive immune responses. We summarize current knowledge on Cu’s roles in cancer and immunity, emphasizing recent insights into how these intersect through Cu-mediated modulation of anticancer immune pathways. Finally, we explore the clinical potential of Cu-based nanomedicines to convert immunologically “cold” tumors into “hot” ones, thereby improving responses to immunotherapy. Realizing this potential will depend on the thoughtful integration of Cu delivery approaches with existing immunotherapeutic strategies. Full article
(This article belongs to the Special Issue Targeted Immune Modulation Strategies for Cancer, Infectious and Autoimmune Diseases)
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36 pages, 1248 KB  
Review
Next-Generation Cancer Treatment: Photoimmunotherapy’s Promise for Unresectable Head and Neck Cancers
by Laura Marinela Ailioaie, Constantin Ailioaie and Gerhard Litscher
Pharmaceutics 2025, 17(6), 716; https://doi.org/10.3390/pharmaceutics17060716 - 29 May 2025
Cited by 5 | Viewed by 4476
Abstract
Traditional oncological therapies have contributed to reducing the global cancer burden; however, they have not achieved complete eradication, nor have they effectively prevented relapses, minimized toxicity, or preserved immune function. Recent advances, particularly the introduction of immune checkpoint inhibitors (ICIs) and CAR-T cell [...] Read more.
Traditional oncological therapies have contributed to reducing the global cancer burden; however, they have not achieved complete eradication, nor have they effectively prevented relapses, minimized toxicity, or preserved immune function. Recent advances, particularly the introduction of immune checkpoint inhibitors (ICIs) and CAR-T cell therapies, have markedly improved clinical outcomes and overall survival in certain cancer subtypes. Nevertheless, response rates remain suboptimal, and adverse immunological events are frequent. This review starts by highlighting the FDA-approved ICIs currently utilized in cancer immunotherapy, emphasizing those that have demonstrated clinical efficacy in recent years. The true focus of our analysis is on the latest clinical applications of near-infrared photoimmunotherapy (NIR-PIT). This emerging modality is evaluated in patients with head and neck cancers (HNC), particularly in cases that are unresectable, locally advanced, or recurrent. Finally, the review explores the current landscape and prospects of NIR-PIT, considering its potential to enhance therapeutic efficacy and extend relapse-free survival. Photoimmunotherapy is a promising, molecularly targeted option for patients with limited prognosis, offering new hope where conventional therapies fail. By synthesizing recent clinical trial data, this work highlights how NIR-PIT could bridge the translational gap between preclinical research and clinical practice. The integration of advanced technologies and interdisciplinary collaboration among researchers, clinicians, and technologists will be critical in optimizing NIR-PIT, improving its accuracy, efficacy, and safety, and ultimately advancing standards of cancer care and patient survival. Full article
(This article belongs to the Special Issue Targeted Immune Modulation Strategies for Cancer, Infectious and Autoimmune Diseases)
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30 pages, 7375 KB  
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
Cited by 9 | Viewed by 4009
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
(This article belongs to the Special Issue Targeted Immune Modulation Strategies for Cancer, Infectious and Autoimmune Diseases)
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46 pages, 1455 KB  
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
Cited by 10 | Viewed by 3752
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
(This article belongs to the Special Issue Targeted Immune Modulation Strategies for Cancer, Infectious and Autoimmune Diseases)
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