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.

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.

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.

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.

Vaccination is one of the most effective medical interventions, saving millions of lives and reducing the morbidity of infections across the lifespan, from infancy to older age. The generation of plasma cells and memory B cells that produce high affinity class switched antibodies is central to this protection, and these cells are the ultimate output of the germinal centre response. Optimal germinal centre responses require different immune cells to interact with one another in the right place and at the right time and this delicate cellular ballet is coordinated by a network of interconnected stromal cells. In this review we will discuss the various types of lymphoid stromal cells and how they coordinate immune cell homeostasis, the induction and maintenance of the germinal centre response, and how this is disorganised in older bodies.

Macrophages are now recognised to be highly heterogeneous, with diverse ontogenies, anatomical locations and characteristics, all of which inform their function. Nerve-associated macrophage subpopulations have been found to exist across tissues, and whilst they appear to have roles in neuronal maintenance and repair, their function is still being elucidated. Although nerve-associated macrophage functions in the Central Nervous System have taken centre-stage, nerve-associated macrophages also interact with peripheral nerves and this field remains relatively understudied. This review discusses recent studies into nerve-associated macrophages across peripheral tissues. These studies identify populations of nerve-associated macrophages in many peripheral tissues, and reveal elegant neuroimmune communication pathways which coordinate functions from infection defence and anti-inflammatory actions to neuronal maintenance for homeostatic tissue function and nerve repair. We highlight nerve-associated macrophage interactions with nerves in peripheral tissues as a rapidly evolving field which could revolutionise our understanding of macrophage function in both homeostasis and disease.

This chapter focuses on the groundbreaking advances in the treatment of cancer via the development of innovative immunotherapies, which include immune checkpoint inhibitors, bispecific antibodies, and cancer vaccines. The chapter begins with an overview of current cancer treatment paradigms and the pressing need for innovative therapeutic strategies. It then explores the principles and latest trends in immunotherapy, highlighting the mechanisms of action and key players in checkpoint blockade therapy. The discussion extends to bispecific antibodies, focusing on their unique mechanisms, developmental challenges, and current clinical applications. The chapter also explores the frontier of cancer vaccines, distinguishing between preventive and therapeutic approaches, and examining the development of personalized vaccines. Finally, the chapter provides insights into future directions in cancer treatment, offering a comprehensive perspective on the evolving landscape of immunotherapy and its potential to transform patient outcomes.

The emergence and re-emergence of infectious diseases present significant global health threats. Understanding their pathogenesis is crucial for developing diagnostics, therapeutics, and preventive strategies. System-level integrative omics analysis offers a comprehensive approach to deciphering virus-host immunometabolic interactions during infections. Multi-omics approaches, integrating genomics, transcriptomics, proteomics, and metabolomics, provide holistic insights into disease mechanisms, host-pathogen interactions, and immune responses. The interplay between the immune system and metabolic processes, termed immunometabolism, has gained attention, particularly in infectious diseases. Immunometabolic studies reveal how metabolic processes regulate immune cell function, shaping immune responses and influencing infection outcomes. Metabolic reprogramming is crucial for immune cell activation, differentiation, and function. Using systems biological algorithms to understand the immunometabolic alterations can provide a holistic view of immune and metabolic pathway interactions, identifying regulatory nodes and predicting responses to perturbations. Understanding these pathways enhances the knowledge of immune regulation and offers avenues for therapeutic interventions. This review highlights the contributions of multi-omics systems biology studies in understanding infectious disease pathogenesis, focusing on RNA viruses. The integrative approach enables personalized medicine strategies, considering individual metabolic and immune variations. Leveraging these interdisciplinary approaches promises advancements in combating RNA virus infections and improving health outcomes, highlighting the transformative impact of multi-omics technologies in infectious disease research.

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.

Cancer immunotherapy recently has emerged as a revolutionary method in oncology. It takes the help of the body's immune system in fighting against tumor cells. Amongst the various approaches, DNA and mRNA vaccines are novel modalities with the potential to revolutionize cancer treatment. They represent one such approach that can result in potent immune responses against tumor-specific antigens. The few but serious translation bottlenecks at the clinical level have been related to stability, in vivo distribution, and efficient delivery systems for DNA and mRNA vaccines. It is against this salient background that this chapter takes readers through recent success stories of DNA and mRNA vaccines, right from the formulation of the vaccine to delivery mechanisms, stability, and bioavailability in cancer immunotherapy. The further challenges that are discussed in this chapter are those of effect in vivo distribution and how such challenges impact therapeutic efficacy. In addition, the new emerging technologies for in vivo distribution and opportunities for optimization of emerging vaccines to clinical use are approached, with the main focus placed on new delivery platforms. The aim of this chapter is to help understand the current landscape and future directions toward DNA and mRNA vaccines in designing more effective and personalized cancer therapies.

The emergence of mRNA-based cancer immunotherapy has transformed the avenue of cancer treatment, offering an innovative strategy that leverages the body's immune system to identify and eradicate tumor cells selectively. Effective delivery of mRNA to specific organs and cells is limited by its instability, low cellular uptake efficiency, and degradation during extracellular transport and endosomal escape. Significant advancements in nanoparticle design have driven the rapid progress of mRNA-based immunotherapies. Nanocarriers have emerged as vital delivery systems, providing enhanced stability, resistance to enzymatic degradation, and efficient mRNA delivery to target cells. This chapter investigates the design, synthesis, and functionalization of different types of nanoparticles, including lipid-based, polymeric, and hybrid nanoparticles and also highlights their unique characteristics and mechanisms for mRNA delivery in cancer immunotherapy. This chapter explores cellular uptake mechanisms, strategies for endosomal escape, and the subsequent translation of mRNA into therapeutic proteins that elicit a vigorous anti-tumor immune response. Recent advances in nanoparticle-based mRNA vaccines are also explored, with an emphasis on research findings and clinical trials that reveal both their potential and challenges. The chapter aims to provide a thorough overview of nanoparticle integration in mRNA-based cancer immunotherapy and also offer insights into future developments and emerging trends in the field.

Fungal infections are increasingly recognised as a major threat to global human health, with several million preventable deaths each year now attributable to fungal diseases. Climate change, global pandemics and increased use of antibiotics and immune-suppressing drugs in modern medicine have all contributed towards recent rises in the number of cases of life-threatening fungal infections. To circumvent these trends, it is imperative that we develop a deeper understanding of the immune responses that operate to protect against fungal invasion if we are to develop adjunctive immune-based therapies for these infections. Recent work has already demonstrated how mechanistic insights into antifungal immune responses can yield therapeutic benefits. This chapter covers the major processes, cells and receptors that are required for successful antifungal immune responses, focusing on recent developments that have driven significant new step-changes in our understanding of how these pathogens are detected and removed from the body.

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.

Malignant melanoma is one of the most aggressive forms of cancer and a leading cause of death from skin tumors. With the rising incidence of melanoma diagnoses, there is an urgent need to develop effective treatments. Among the most modern approaches are cancer vaccines, which aim to enhance cell-mediated immunity. Recently, mRNA-based cancer vaccines have gained significant attention due to their rapid production, low manufacturing costs, and ability to induce both humoral and cellular immune responses. These vaccines hold great potential in melanoma treatment, yet their application faces several challenges, including mRNA stabilization, delivery methods, and tumor heterogeneity. The recent success of mRNA vaccines in combating COVID-19 has renewed interest in their potential for cancer immunotherapy. In particular, mRNA cancer vaccines offer high specificity and better efficacy compared to traditional treatments. They can target tumor-specific neoantigens, prompting a robust immune response. This chapter reviews the mechanism of action of mRNA vaccines, advancements in adjuvant identification, and innovations in delivery systems such as lipid nanoparticles. It also discusses ongoing clinical trials evaluating the efficacy of mRNA-based vaccines in melanoma, highlighting promising early-phase results. Despite their potential, the development of mRNA cancer vaccines faces significant obstacles. Tumor heterogeneity, immunosuppressive tumor microenvironments, and practical issues like vaccine administration and clinical evaluation methods are major barriers to success. By addressing these challenges and advancing innovations, mRNA cancer vaccines hold promise for transforming melanoma treatment. A careful balance between the opportunities and challenges will be key to unlocking the full potential of mRNA vaccines in 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.

Cancer's complex nature and personal variety make it among the toughest cancers to conquer. Innovative treatment strategies can be achieved through new biotechnology developments. DNA and mRNA vaccinations deliver an opportunity to take a new path for cancer. The ways in which DNA and mRNA vaccinations generate immune reactions that specifically focus on cancer cells are discussed in this section. This chapter focuses on the development and creation of these vaccines. We will focus on the latest research that proves the effectiveness of these vaccines and their safety over different types of cancer. Also, we discuss the technological and biological barriers in the process of vaccine development that hinder the development of these vaccines, such as the stability of delivery methods and a patient-specific design for vaccines. DNA and mRNA vaccinations are an important therapeutic approach against cancer with genetic information. They offer an opportunity for the future to develop tailored as well as more efficient treatment options.

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.

The immune system requires a complex network of specialized cell types to defend against a range of threats. The specific roles and destinies of these cell types are enforced by a constellation of gene regulatory programs, which are orchestrated through lineage-specifying transcription factors. T Cell Factor 1 (TCF1) is a central transcription factor in many of these programs, guiding the development and functionality of both adaptive and innate lymphoid cells. This review highlights recent insights into the function of TCF1 in a variety of lymphoid cell subsets and its potential for translational applications in immune disorders and cancer.

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.

Interferon regulatory factor-8 (IRF8) is the lineage determining transcription factor for the type one classical dendritic cell (cDC1) subset, a terminal selector for plasmacytoid dendritic cells and important for the function of monocytes. Studies of Irf8 gene regulation have identified several enhancers controlling its activity during development of progenitors in the bone marrow that precisely regulate expression at distinct developmental stages. Each enhancer responds to distinct transcription factors that are expressed at each stage. IRF8 is first expressed in early progenitors that form the monocyte dendritic cell progenitor (MDP) in response to induction of the transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) acting at the Irf8 +56 kb enhancer. IRF8 levels increase further as the MDP transits into the common dendritic cell progenitor (CDP) in response to E protein activity at the Irf8 +41 kb enhancer. Upon Nfil3-induction in CDPs leading to specification of the cDC1 progenitor, abrupt induction of BATF3 forms the JUN/BATF3/IRF8 heterotrimer that activates the Irf8 +32 kb enhancer that sustains Irf8 autoactivation throughout the cDC1 lifetime. Deletions of each of these enhancers has revealed their stage dependent activation. Surprisingly, studies of compound heterozygotes for each combination of enhancer deletions revealed that activation of each subsequent enhancer requires the successful activation of the previous enhancer in strictly cis-dependent mechanism. Successful progression of enhancer activation is finely tuned to alter the functional accessibility of subsequent enhancers to factors active in the next stage of development. The molecular basis for these phenomenon is still obscure but could have implications for genomic regulation in a broader developmental context.

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.