Advances in Immunology最新文献

The number of immuno-oncology medication approvals in current years has increased, indicating the immense potential of cancer immunotherapy. Nucleic acid therapy has advanced significantly in the interim. The diverse capabilities of nucleic acid therapies, gene-editing guide RNA (gRNA), immunomodulatory DNA/RNA, messenger RNA (mRNA), microRNA and siRNA, plasmids, and antisense oligonucleotides (ASO), for modification of immune responses and change the target endogenous or synthetic gene's expression, make them appealing. These skills can be extremely important in the creation of innovative immunotherapy approaches. To be effective, these treatments must, however, overcome a number of delivery challenges, such as quick in vivo disintegration, inadequate absorption inside target cells, necessary nuclear entrance, along with possible in-vivo toxic potential in tissues and cells that are healthy. Several of these obstacles have been addressed by the development of nanoparticle delivery methods, which allow nucleic acid therapies to be safely and successfully delivered to immune cells. The nucleic acid applications for medicines employed for immunotherapy against cancer are covered in this chapter, along with the development of nanoparticle platforms that carry genome editing, mRNA, and DNA systems for improving the efficacy and safety profile in various therapies.

Lipid nanoparticles (LNPs) to deliver messenger RNA (mRNA) have emerged as a transformative strategy in cancer immunotherapy. This chapter explores the pivotal role of LNPs in enabling the efficient and targeted delivery of mRNA for cancer treatment, offering an innovative alternative to traditional therapies. LNPs protect mRNA from degradation, ensure its safe passage into the cytoplasm of target cells, and promote the expression of tumor-specific antigens that can activate the immune system against cancer cells. This chapter covers the fundamental properties of lipid nanoparticles, including their composition, structure, and functional modifications, as well as their mechanism of action in mRNA delivery. It also delves into optimizing LNPs to enhance targeting specificity, reduce toxicity, and improve therapeutic efficacy in cancer immunotherapy. Advances in the design of these nanoparticles, including innovations in surface functionalization and their role in overcoming tumor microenvironment barriers, are discussed. The chapter further examines preclinical and clinical applications of LNP-mediated mRNA cancer vaccines and therapies, highlighting recent successes and case studies. In addition, challenges such as ensuring efficient delivery, managing off-target effects, and addressing potential immune reactions are explored. Finally, future perspectives on developing more advanced LNPs and mRNA therapies, including their potential for personalized cancer treatments, are discussed. By providing an in-depth understanding of the current state and future potential of LNP-mediated mRNA delivery, this chapter aims to offer valuable insights into how this technology is shaping the future of cancer immunotherapy.

Biological and societal issues are involved when we refer to a condition as cancer, which connotes loss, complexity, and uncertainty. In recent decades, the number of melanomas has climbed. Cancer treatment vaccines have induced immune responses against tumor-associated but not tumor-specific antigens. Cancer therapy may use mRNA vaccines after COVID-19 pandemic regulation advancements. Therapy mRNA cancer vaccines as advanced immunotherapies gain prominence. Using messenger RNA, the mRNA-4157/V940 cancer vaccine encodes 34 patient-specific tumor euroantigens. mRNA-4157/V940, like the COVID-19 vaccination, instructs the immune system to distinguish healthy and malignant cells using messenger RNA. T cell responses are tailored to a patient's tumor mutational pattern using this unique immunization. The drug suppresses PD-1, PD-L1, and PD-L2. T lymphocytes activated by pembrolizumab may affect cancer and non-cancerous cells. Early clinical trials suggest pembrolizumab and mRNA-4157/V940 may boost T cell-mediated cancer killing. Knowing the status and problems of melanoma therapeutic mRNA cancer vaccines in clinical trials is critical. In this chapter, we have focused on preclinical and clinical advances that have revealed mRNA melanoma vaccine manufacturing issues and solutions.

for delivery of plasmid DNA and mRNA transform biology and medicine, offering powerful tools for gene therapy, vaccine development, cancer immunotherapy, and regenerative medicine. Plasmid DNA provides a relatively stable and sustained expression of the genes which also provides the basic groundwork for long-lasting therapeutic. At the same time, mRNA has also demonstrated more appropriateness for dynamic and time-sensitive applications due to its short-lived and accurate translation capabilities, such as during the development of mRNA-based COVID-19 vaccines. Despite their unique advantages, however, the efficient delivery of these biomolecules poses challenges including immune system activation, enzymatic degradation, and limited cellular uptake. The structural and functional features of plasmid DNA and mRNA highlighted the positive functions that underpin their complementary roles in next-generation biomedical applications. In addition, it highlights the novel delivery routes across lipid nanoparticles, polymeric systems, biomimetic carriers, and hybrid applied sciences which can resolve long-standing challenges to efficient distribution. Emerging technologies such as CRISPR gene editing, self-amplifying RNA, and multiplexed nanoparticles are also increasing the utility of these systems. Significant advances in the delivery of plasmid DNA and mRNA molecules have revolutionized vaccine development, opened new avenues in personalized medicine, and have also inspired a future with engineerable tissues. As these innovations develop, they are predicted to go beyond current limitations and bring around a fresh era of accurate medication taking on one of the global healthcare's most complex challenges. Our revolutionary delivery methods provide stability and simplicity, transforming medical advances.

mRNA carries genetic information and is used for the synthesis of proteins, fragments of proteins, and peptides in the scope of biotechnology and medicine. Once introduced into cells, this mRNA gets translated into a corresponding protein with cellular machinery. All kinds of mRNA encoding any protein, peptide, and fragment of proteins have been designed to be used for various therapeutic goals, including cancerous diseases, immunotherapy, vaccine preparation, tissue engineering, and genetic disorders, among others. These vaccines encode tumor-specific antigens that stimulate the immune system to recognize and attack cancer cells. Additionally, mRNA can be designed to produce proteins that modulate immune checkpoints, thereby enhancing the immune system's ability to target cancer cells. Synthetic mRNA can also engineer immune cells, such as T cells, to improve their cancer-fighting capabilities. For instance, mRNA can be engineered to generate CAR T cells targeting specific antigens that are expressed in the cancer. Designed mRNA can encode functional proteins in patients suffering from genetic disorders characterized by an absence or defect in a particular protein. However, mRNA is intrinsically unstable and may require special mechanisms to protect it from degradation. mRNA delivery to target cells remains a challenge. Engineered nanocarriers containing mRNA can improve the efficiency and enable the delivery to specific sites, that can provide a stimulant or substance for therapeutic purposes. This combination may improve their stability and efficacy in multiple applications of therapies. The following chapter throws light on basic advances in mRNA-based cancer therapy and provides insights into the nanotherapeutics using mRNA in key preclinical developments and the evolving clinical landscape.

Macrophages are essential immune cells that arise early during embryogenesis and persist as tissue-resident cells into adulthood. This chapter explores macrophage development, focusing on their roles in the nervous system. We describe their distinct origins from early hematopoietic waves and their differentiation into specialized populations such as microglia and border-associated macrophages (BAMs) in the central nervous system (CNS) as well as nerve-associated macrophages in the peripheral (PNS) and enteric nervous system (ENS). These macrophage populations are crucial for tissue development, maintenance, and repair mediating their effects through intricate cellular communication networks with neighboring cells. Furthermore, we discuss how disruptions in macrophage development - driven by factors such as maternal obesity, stress, or environmental pollutants - can have profound and lasting impacts on neurodevelopmental and neurodegenerative outcomes. Gaining a deeper understanding of these developmental processes offers valuable insights into nervous system integrity and reveals potential therapeutic avenues for mitigating disease-related consequences.

Cancer vaccines have become a promising approach in the fight against cancer, harnessing the remarkable capability of the human immune system to recognize and eliminate cancer cells. These vaccines are specifically engineered to activate the immune response against malignant cells, marking a significant advancement in contemporary research. By capitalizing on the unique ability of the immune system to detect and eliminate cancer cells, these vaccines present promising prospects for both prevention and therapeutic intervention. Recent advancements have provided profound insights into how these vaccines can be tailored to target specific cancer types, enhancing their efficacy and minimizing side effects. This innovative strategy holds the potential to transform cancer care, offering new avenues for durable and effective treatments. This chapter delves into the historical context of cancer vaccine research, discussing various types of cancer vaccines, their mechanisms of action, and the role of adjuvants and delivery systems in enhancing vaccine efficacy. It also covers tumor immunogenicity, how tumor cells evade the immune system, and the combined use of cancer vaccines with other treatment approaches. The chapter aims to elucidate the potential of cancer vaccines to revolutionize cancer treatment and improve patient outcomes.

Lately, the urgency of precision medicine in cancer care through immunotherapy has reformed the arena of oncology. Although immunomodulatory therapeutics in cancer have been preliminarily concentrated on T-cells, emerging evidences have suggested that intra-tumoral B-cells and plasma cells have significant contributions in cancer prognosis primarily through the production of antibodies. B-cell oriented cancer vaccines have been used in early clinical trials of breast and other cancers after multiple preclinical studies. Passive immunotherapy via administration of monoclonal antibodies (mAbs) and emergence of anti-idiotypic antibodies have led to considerable advancement in oncotherapy. Endogenous production of mAbs would be of significant benefit in recurrent or residual malignancies and permanent infusion would help in the overcoming of issues related to pharmacodynamic variations observed in case of intravenous inoculations of bi or tri specific mAbs. This has directed towards the development of genome reprogrammed B-cells with the capability of yielding therapeutic mAbs independently. Genetic alteration through clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) nucleases have enabled the introduction of transgenes into B-cell genome thereby stimulating the plasma cells to produce exogenous remedial antibodies. It also facilitates ex vivo B-cell editing to elevate specificities of antigen receptors and generate target specific antibody responses which cannot normally be evoked in patient's immune system. Hence, genome-altered B-cells possess the potential of engineered therapeutics against certain malignancies. Co-operation of B-cells in T-cell based vaccines are ultimate need for vaccine success. In this chapter, the mechanisms, challenges and potential advantages of B-cell editing in cancer immune therapy shall be explored. The prospects of B-cell editing in onco-therapy will be clearly elucidated with all its strength and weaknesses.

Vaccination is arguably the most effective intervention in reducing the impact of infectious diseases. However, many vaccines provide only partial or transient protection, prompting the need for more effective solutions based on our growing understanding of the pivotal role of CD4⁺ T follicular helper (Tfh) cells in humoral immunity and how they interact with B cells. Here we review how γδ T cells can boost antibody responses via crosstalk with both Tfh and B cells, which could lead to new adjuvant strategies to improve vaccination efficacy, achieve long-lasting protective immunity and prevent major infectious diseases of global importance.

Advancements in mRNA-based therapeutics have greatly enhanced cancer immunotherapy by using the immune system to specifically target and eradicate cancer cells. There has been notable advancement in tailoring and administering mRNA to treat cancer. Codon optimization, chemical alterations, and sequence manipulation are complex design methodologies employed in the production of mRNA vaccines and treatments. The goal is to improve the ability of the chemicals to stimulate an immune response, increase their ability to be translated into practical applications, and boost their stability. Lipid nanoparticles (LNPs) are currently the most efficient means of delivering mRNA because they can withstand degradation, enhance cellular uptake, and facilitate endosomal escape. Scientists are currently investigating the possibility of using alternate methods of delivering substances, including as exosomes, lipoplexes, and polymeric nanoparticles, to enhance the ability to target specific tissues and minimize unwanted negative consequences. In addition, recent clinical trials and preclinical investigations have demonstrated encouraging findings in terms of the advancement of strong anti-tumor immune responses, long-lasting tumor shrinkage, and enhanced patient outcomes. The remaining challenges involve optimizing the equilibrium between tolerance and immunological activation, addressing systemic toxicity, and expanding manufacturing techniques. The upcoming study seeks to improve the design and dissemination of mRNA, include it in combination drugs, and investigate its therapeutic uses outside cancer. The advancement in cancer treatment represents a change in the current approach, highlighting the significant impact of mRNA technology in revolutionizing immunotherapy and enabling tailored cancer treatments.