Innovative gene engineering and drug delivery systems for dendritic cells in cancer immunotherapy – Journal of Biomedical Science

Advancing Cancer Immunotherapy Through Dendritic Cell Modulation: A Strategy for Achieving Sustainable Development Goal 3

The global burden of cancer represents a significant challenge to achieving the United Nations’ Sustainable Development Goal 3 (SDG 3), which aims to ensure healthy lives and promote well-being for all at all ages. Specifically, Target 3.4 calls for a one-third reduction in premature mortality from non-communicable diseases, including cancer. Dendritic cell (DC)-based immunotherapy has emerged as a promising therapeutic modality to address this global health issue. This report outlines the role of DCs in cancer immunity, the challenges hindering their efficacy, and innovative strategies being developed to enhance their therapeutic potential, thereby contributing to the targets of SDG 3.

The Foundational Role of Dendritic Cells in Antitumor Immunity

Dendritic cells are professional antigen-presenting cells (APCs) that are critical for initiating and regulating adaptive immune responses. Their function is central to the cancer-immunity cycle and represents a key leverage point for therapeutic intervention.

Core Functions of Dendritic Cells:

• Antigen Capture and Processing: DCs capture tumor-associated antigens (TAAs) released from cancer cells.
• Antigen Presentation: They process these antigens and present them via Major Histocompatibility Complex (MHC) class I and class II molecules to T cells.
• T Cell Activation: Through a process known as cross-presentation, DCs activate naive CD8+ cytotoxic T lymphocytes, which are essential for killing cancer cells.
• Immune Response Orchestration: DCs secrete cytokines that shape the nature of the T cell response, promoting a robust antitumor environment.

Challenges to Dendritic Cell Efficacy in the Context of Global Health Goals

Despite their potential, the clinical efficacy of DC-based vaccines has been limited. These limitations are primarily due to the complex and immunosuppressive nature of the tumor microenvironment (TME), which directly undermines progress toward SDG 3 by rendering promising treatments less effective.

Key Obstacles:

1. TME-Induced Dysfunction: The TME impairs DC function through various mechanisms, including metabolic reprogramming (e.g., lipid accumulation, lactic acid), hypoxia, and the secretion of immunosuppressive factors like TGF-β and IL-10.
2. Inhibitory Signaling Pathways: Tumors exploit immune checkpoint pathways (e.g., PD-L1) and other signaling molecules (e.g., CD47, TIM-3) to induce DC tolerance and suppress T cell activation.
3. Impaired Migration and Maturation: DCs within the TME often exhibit an immature phenotype and have reduced migratory capacity to lymph nodes, preventing the effective initiation of a systemic antitumor response.
4. Manufacturing and Delivery Hurdles: The generation of conventional ex vivo DC vaccines is complex and costly, posing a barrier to widespread, equitable access, which is a core principle of the SDGs.

Enhancement Strategies: Fostering Innovation for Sustainable Health (SDG 9)

Overcoming the challenges to DC immunotherapy requires significant scientific and technological advancement, aligning with Sustainable Development Goal 9 (SDG 9), which promotes industry, innovation, and infrastructure. Research efforts are focused on genetically engineering DCs and developing novel delivery systems to enhance their potency and resilience.

Genetic Engineering of Dendritic Cells

Advanced gene-editing technologies are being employed to reprogram DCs for superior therapeutic performance.

• CRISPR/Cas9 and TALENs: These tools are used to knock out inhibitory genes (e.g., PD-L1, SOCS1) or knock in genes that enhance DC function, such as those for co-stimulatory molecules (CD40L, CD70) or pro-inflammatory cytokines (IL-12).
• Viral and Non-Viral Transduction: Lentiviral and adenoviral vectors, as well as mRNA electroporation, are used to modify DCs to express specific antigens or immunostimulatory molecules, thereby increasing their ability to prime T cells.

Nanotechnology-Based Delivery Systems

Nanoparticles offer a versatile platform for delivering antigens and adjuvants directly to DCs, improving vaccine efficacy and manufacturability.

1. Lipid Nanoparticles (LNPs): LNPs are effective for delivering mRNA-based vaccines and adjuvants (e.g., STING agonists) that can activate DCs and promote robust immune responses.
2. Polymeric Nanoparticles: Materials like PLGA can be formulated into nanoparticles to co-deliver tumor antigens and immune-stimulating agents, with surface modifications to target specific DC subsets (e.g., via DEC-205, CLEC9A).
3. Extracellular Vesicles (EVs) and Exosomes: Engineered exosomes derived from DCs or other cell types are being developed as “natural” nanocarriers for delivering antigens, RNA, or CRISPR/Cas9 components to modulate immune responses.
4. Inorganic Nanoparticles: Gold, silica, and magnetic nanoparticles are being explored for their ability to facilitate antigen delivery, track DC migration via imaging, and act as adjuvants.

Conclusion: A Collaborative Path Toward Global Health and Well-being

Enhancing the efficacy of dendritic cell-based cancer immunotherapy is a critical frontier in oncology that directly supports the ambitions of SDG 3. By leveraging innovations in genetic engineering and nanotechnology, as encouraged by SDG 9, researchers are developing next-generation therapies that can overcome the immunosuppressive barriers of the tumor microenvironment. The global, collaborative nature of this research, as evidenced by numerous international studies, also embodies the spirit of SDG 17 (Partnerships for the Goals). Continued investment and international cooperation in these advanced therapeutic strategies are essential for reducing the global cancer burden and building a more sustainable and healthier future for all.

Sustainable Development Goals (SDGs) Addressed in the Article

The provided article, which consists of a comprehensive list of scientific references, primarily revolves around advanced medical research into cancer immunotherapy. The analysis of the reference titles and their subject matter reveals connections to several Sustainable Development Goals (SDGs), with a primary focus on health, innovation, and global collaboration.

• SDG 3: Good Health and Well-being

  This is the most prominent SDG connected to the article. The overarching theme of the references is the development of advanced treatments for cancer, a major non-communicable disease. The research cited explores dendritic cell-based vaccines, immunotherapy strategies, and novel drug delivery systems, all of which are aimed at improving health outcomes and reducing mortality from cancer. For instance, references such as “Dendritic cell–based immunotherapy: state of the art and beyond” (Ref. 5) and “Research progress on dendritic cell vaccines in cancer immunotherapy” (Ref. 8) directly address the goal of ensuring healthy lives by advancing medical treatments.

• SDG 9: Industry, Innovation, and Infrastructure

  This goal, particularly its emphasis on scientific research and innovation, is highly relevant. The article’s references highlight cutting-edge scientific and technological advancements. Topics include “Engineering dendritic cell vaccines to improve cancer immunotherapy” (Ref. 10), the use of nanotechnology such as “Optimized lipid nanoparticles enable effective CRISPR/Cas9-mediated gene editing in dendritic cells” (Ref. 142), and advancements in gene-editing technologies like CRISPR/Cas9. These references demonstrate a strong focus on enhancing scientific research and upgrading technological capabilities to solve complex health challenges, which is a core component of SDG 9.

• SDG 17: Partnerships for the Goals

  The nature of the article as a list of over 300 scientific publications from various international journals, involving numerous authors from different institutions worldwide, implicitly points to global collaboration. Scientific progress, especially in a complex field like cancer immunotherapy, relies on the sharing of knowledge, data, and innovations across borders. This collaborative effort is essential for achieving the other SDGs and is the central theme of SDG 17, which seeks to strengthen the means of implementation and revitalize the global partnership for sustainable development.

Specific Targets Identified

Based on the content of the article’s references, several specific SDG targets can be identified as being directly addressed by the research discussed.

1. Target 3.4: Reduce premature mortality from non-communicable diseases

   Explanation: This target aims to reduce by one-third premature mortality from non-communicable diseases (NCDs) through prevention and treatment by 2030. Cancer is one of the leading NCDs responsible for premature deaths globally. The entire body of research cited in the article, focusing on developing more effective cancer treatments like “Sipuleucel-T immunotherapy for castration-resistant prostate cancer” (Ref. 28) and exploring mechanisms to overcome tumor-induced immunosuppression, directly contributes to this target by seeking to improve survival rates and the quality of life for cancer patients.

2. Target 3.b: Support research and development of vaccines and medicines

   Explanation: This target calls for supporting the research and development (R&D) of vaccines and medicines for diseases that affect a large portion of the global population. The article is a testament to intensive R&D efforts in the field of oncology. References like “Dendritic cell vaccines: a shift from conventional approach to new generations” (Ref. 25) and “mRNA-based therapeutics—developing a new class of drugs” (Ref. 274) explicitly detail the ongoing work to create new classes of therapeutic cancer vaccines and medicines.

3. Target 9.5: Enhance scientific research and upgrade technological capabilities

   Explanation: This target encourages enhancing scientific research and upgrading the technological capabilities of industrial sectors. The research cited is at the forefront of biomedical innovation, utilizing sophisticated technologies. For example, references discuss “CRISPR-based functional genomics in human dendritic cells” (Ref. 139), “Nanoparticles for dendritic cell-based immunotherapy” (Ref. 189), and “Exosome-based delivery strategies for tumor therapy” (Ref. 269). This work directly contributes to upgrading the technological toolkit available for medical science and encourages further innovation in the healthcare and biotechnology sectors.

Indicators for Measuring Progress

While the article itself does not provide quantitative data, it implies several indicators that could be used to measure progress toward the identified targets.

• Implied Indicators for Target 3.4

  • Development and success rates of new cancer therapies: The numerous references to clinical trials (e.g., Ref. 40, 317, 318) suggest that the number of new immunotherapies, vaccines, and drug delivery systems entering and successfully completing clinical trials would be a direct indicator of progress.
  • Cancer mortality rates: The ultimate measure of success for the research discussed would be a reduction in the mortality rate attributed to cancer, which is the core aim of Target 3.4’s indicator 3.4.1.

• Implied Indicators for Target 3.b

  • Volume of research and development: The sheer number of recent publications (many from 2022-2025) serves as a proxy indicator for the total investment and human resources dedicated to R&D for cancer treatments. This aligns with indicator 3.b.2, which measures total net official development assistance to medical research and basic health sectors.
  • Number of patents and new drug approvals: The development of novel technologies, such as the “STING-activating polymers” (Ref. 208) and “engineered exosomes” (Ref. 290), would lead to patents and, eventually, new drug approvals by regulatory bodies, which can be tracked as a measure of R&D output.

• Implied Indicators for Target 9.5

  • Adoption of advanced technologies in research: The prevalence of articles on topics like CRISPR, nanotechnology, and mRNA delivery (e.g., Ref. 142, 187, 274) indicates the integration of these advanced technologies into mainstream medical research. The proportion of R&D spending allocated to these technologies could serve as a quantifiable indicator.
  • Number of researchers in high-tech medical fields: An increase in the number of researchers and scientists working in fields like immuno-oncology, nanomedicine, and gene editing, as suggested by the extensive author lists, would be an indicator of growing R&D capacity (Indicator 9.5.2).

Summary Table of SDGs, Targets, and Indicators

Source: jbiomedsci.biomedcentral.com