AbDPP: Target-oriented antibody design with pretraining and prior biological structure knowledge.

Antibodies represent a crucial class of complex protein therapeutics and are essential in the treatment of a wide range of human diseases. Traditional antibody discovery methods, such as hybridoma and phage display technologies, suffer from limitations including inefficiency and a restricted exploration of the immense space of potential antibodies. To overcome these limitations, we propose a novel method for generating antibody sequences using deep learning algorithms called AbDPP (target-oriented antibody design with pretraining and prior biological knowledge). AbDPP integrates a pretrained model for antibodies with biological region information, enabling the effective use of vast antibody sequence data and intricate biological system understanding to generate sequences. To target specific antigens, AbDPP incorporates an antibody property evaluation model, which is further optimized based on evaluation results to generate more focused sequences. The efficacy of AbDPP was assessed through multiple experiments, evaluating its ability to generate amino acids, improve neutralization and binding, maintain sequence consistency, and improve sequence diversity. Results demonstrated that AbDPP outperformed other methods in terms of the performance and quality of generated sequences, showcasing its potential to enhance antibody design and screening efficiency. In summary, this study contributes to the field by offering an innovative deep learning-based method for antibody generation, addressing some limitations of traditional approaches, and underscoring the importance of integrating a specific antibody pretrained model and the biological properties of antibodies in generating novel sequences. The code and documentation underlying this article are freely available at https://github.com/zlfyj/AbDPP.

Determinants of prescribing decisions for off-patent biological medicines in Belgium: a qualitative study.

BACKGROUND: A competitive market for off-patent biologicals leads to more affordable and high-quality healthcare. In recent years, Belgium has been characterized by its low use of biosimilars and by its shifts from off-patent biologicals toward new alternative therapies. Yet, the prescribing decisions involved in these observations are poorly understood. This study aims to better understand prescribing choices among Belgian physicians in the ambulatory care setting. METHODS: This study consisted of two phases. First, a scoping literature review to identify determinants of prescribing choices was conducted. Scientific databases (Embase and PubMed) were searched until 4 November 2021. Second, the nominal group technique (NGT) was employed during focus group discussions with Belgian physicians to consider and validate these determinants for off-patent biologicals in the Belgian context. The qualitative data resulting from the literature review and focus group discussions were analyzed using the thematic framework method. RESULTS: Fifty-three scientific articles that discussed elements that determine prescribing choices were identified. Out of these, 17 determinants of prescribing choices were found. These were divided into five categories: (1) product-related, (2) physicians' personal, (3) healthcare system-related, (4) patient-related, and (5) determinants related to the pharmaceutical company or brand. Nineteen Belgian physicians from different therapeutic areas that regularly prescribe biologicals then participated in focus group discussions. Using the NGT, the group discussions revealed that prescribing choices for off-patent biologicals are determined by a complex set of elements. Clinical data, geographical region, working environment, pharmaceutical marketing, patient profile, clinical guidelines, and preference of key opinion leaders (KOL) were considered most influential. Physicians indicated that the importance of these determinants differs depending on product classes or therapeutic domain. CONCLUSIONS: Multiple elements determine the choice of an off-patent biological or biosimilar product. The importance of each of these determinants varies depending on the context in which the prescribing choice is made. To increase the prescription of best-value biologicals in the Belgian ambulatory care, a set of synergistic measures is required including information for healthcare providers (HCP) and patients, prescribing feedback, prescribing targets, tangible incentives, KOL involvement, guidelines regarding pharmaceutical promotion, and regular revision of reimbursement modalities.

Ozone in Medicine. The Low-Dose Ozone Concept and Its Basic Biochemical Mechanisms of Action in Chronic Inflammatory Diseases.

Low-dose ozone acts as a bioregulator in chronic inflammatory diseases, biochemically characterized by high oxidative stress and a blocked regulation. During systemic applications, "Ozone peroxides" are able to replace H2O2 in its specific function of regulation, restore redox signaling, and improve the antioxidant capacity. Two different mechanisms have to be understood. Firstly, there is the direct mechanism, used in topical treatments, mostly via radical reactions. In systemic treatments, the indirect, ionic mechanism is to be discussed: "ozone peroxide" will be directly reduced by the glutathione system, informing the nuclear factors to start the regulation. The GSH/GSSG balance outlines the ozone dose and concentration limiting factor. Antioxidants are regulated, and in the case of inflammatory diseases up-regulated; cytokines are modulated, here downregulated. Rheumatoid arthritis RA as a model for chronic inflammation: RA, in preclinical and clinical trials, reflects the pharmacology of ozone in a typical manner: SOD (superoxide dismutase), CAT (catalase) and finally GSH (reduced glutathione) increase, followed by a significant reduction of oxidative stress. Inflammatory cytokines are downregulated. Accordingly, the clinical status improves. The pharmacological background investigated in a remarkable number of cell experiments, preclinical and clinical trials is well documented and published in internationally peer reviewed journals. This should encourage clinicians to set up clinical trials with chronic inflammatory diseases integrating medical ozone as a complement.

Improving the power to establish clinical similarity in a Phase 3 efficacy trial by incorporating prior evidence of analytical and pharmacokinetic similarity.

To improve patients' access to safe and effective biological medicines, abbreviated licensure pathways for biosimilar and interchangeable biological products have been established in the US, Europe, and other countries around the world. The US Food and Drug Administration and European Medicines Agency have published various guidance documents on the development and approval of biosimilars, which recommend a "totality-of-the-evidence" approach with a stepwise process to demonstrate biosimilarity. The approach relies on comprehensive comparability studies ranging from analytical and nonclinical studies to clinical pharmacokinetic/pharmacodynamic (PK/PD) and efficacy studies. A clinical efficacy study may be necessary to address residual uncertainty about the biosimilarity of the proposed product to the reference product and support a demonstration that there are no clinically meaningful differences. In this article, we propose a statistical strategy that takes into account the similarity evidence from analytical assessments and PK studies in the design and analysis of the clinical efficacy study in order to address residual uncertainty and enhance statistical power and precision. We assume that if the proposed biosimilar product and the reference product are shown to be highly similar with respect to the analytical and PK parameters, then they should also be similar with respect to the efficacy parameters. We show that the proposed methods provide correct control of the type I error and improve the power and precision of the efficacy study upon the standard analysis that disregards the prior evidence. We confirm and illustrate the theoretical results through simulation studies based on the biosimilars development experience of many different products.

Effects of the Usage of l-Cysteine (l-Cys) on Human Health.

This review summarizes recent knowledge about the use of the amino acid l-Cysteine (l-Cys) through diet, nutritional supplements or drugs with the aim to improve human health or treat certain diseases. Three databases (PubMed, Scopus, and Web of Science) and different keywords have been used to create a database of documents published between 1950 and 2017 in scientific journals in English or Spanish. A total of 60,885 primary publications were ultimately selected to compile accurate information about the use of l-Cys in medicine and nutritional therapies and to identify the reported benefits of l-Cys on human health. The number of publications about the use of l-Cys for these purposes has increased significantly during the last two decades. This increase seems to be closely related to the rise of nutraceutical industries and personalized medicine. The main evidence reporting benefits of l-Cys usage is summarized. However, the lack of accurate information and studies based on clinical trials hampers consensus among authors. Thus, the debate about the role and effectiveness of supplements/drugs containing l-Cys is still open.

[Trastuzumab and its biosimilars]. / Trastuzumab and its biosimilars.

Trastuzumab is a monoclonal antibody used as a standard treatment for breast and metastatic gastric cancer when the cancer cells overexpress HER2, a membrane-bound receptor activated by EGF family of ligands. Due to the high cost of the therapy and no refund of the drug in many countries, there is still a large group of patients who do not have the opportunity to receive trastuzumab. A biosimilar is a medical product highly similar to another already approved biological medicine. Biosimilars are approved according to the same standards of pharmaceutical quality, safety and efficacy that apply to all biological medicines. Clinically effective biosimilars may expand patient access to trastuzumab therapy. In the coming months, European Medicines Agency (EMA) continues to increase the number of biosimilar approvals for trastuzumab, helping to promote competition that can lower therapy costs.

Biosimilars to recombinant human FSH medicines: comparable efficacy and safety to the original biologic.

Two recombinant follicle-stimulating hormone (rFSH)-bearing similar biological medicines (biosimilars) have been authorized by the European Commission. Biosimilar is a regulatory concept alluding to the evidence-based high-standard comparability studies needed to demonstrate its equivalence to a reference original biologic. Because biosimilar development represents a shift from the long-lasting existing paradigms, a thorough understanding of the science behind it will contribute to helping prescribers make informed treatment choices. Contrary to chemically-synthesized medicines, biologics are subject to an inherent molecular variability. From the experience with original biologics, regulatory authorities have accumulated a wealth of knowledge as to what minor batch-to-batch physicochemical variations may be therapeutically acceptable in a given product. Furthermore, in spite of analytically detectable differences, the two original rFSH-bearing medicines currently on the market share fundamentally the same therapeutic profile. Unlike those original medicines, a biosimilar of an rFSH product and the corresponding reference biologic share essentially the same active pharmaceutical ingredient. They are also administered via the same route, at the same dose, and for the same indications. This article revises the background evidence over which the biosimilarity principle has been built, and highlights the therapeutic potential for follitropin biosimilars in order to reassure physicians on their benefit.

Biosimilar monoclonal antibodies (mAbs) in oncology.

Biological medicines are derived from living cells and organisms. Monoclonal antibodies (mAbs) are biological agents that are widely used to treat malignancies including non-Hodgkin's lymphomas and chronic lymphocytic leukaemia. They are effective but expensive. The patents for many mAbs are expiring, so biosimilar medicines, which contain a version of the active ingredient of the original drug, are being developed. Biological medicines cannot be assessed in the same way as standard generic medications because they are difficult to copy and can change over time. A pathway regulates how biosimilars are assessed and compared with the original drug to ensure they are highly similar and have no clinically meaningful differences in terms of structure, function, pharmacodynamics and mechanism of action, pharmacokinetic properties, clinical efficacy and safety. Truxima® ▾(rituximab), the first biosimilar monoclonal antibody to be approved for use in the UK in an oncology setting, is biosimilar to intravenous (IV) rituximab; rituximab improves the effectiveness of standard chemotherapy for lymphoma. The two drugs are comparable in efficacy and safety and have the same indications, dosing regimen and storage procedures.

Risk of tuberculosis in patients treated with biological medicines.

OBJECTIVE: The number of medicines used for biological therapy is constantly increasing. Biologic medicines selectively block the immunological processes leading to autoimmune manifestations with tissue damage or block the progression of haemato-oncological or other malignancies. Biological medicines are usually monoclonal antibodies or inhibitors of certain cytokines, cell receptors and enzymes. Their administration results in immunosuppression associated with increased risk of infectious complications, including tuberculosis. Assessment of the risk of tuberculosis associated with biological medicines is an important part of the medical decision done by pneumologist. We describe the risks of different biologicals and suggest the possible necessary steps in evaluating the risk of tuberculosis in individual patient (Ref. 18).

Biosimilars Would Reduce Health Care Costs But Are Yet Poorly Known - Patient Survey Study Among Biological Medicine Users.

Background: From the beginning of the year 2024, gradually implemented amendment to the Medicines Act will enable interchange of biological medicines in pharmacies in Finland. The legislative change aims to reduce health care costs. Methods: Opinions of the biological medicine users regarding substitution in pharmacies and knowledge about biological medicines were determined by a patient survey in community pharmacies and via patient organizations in Finland. Results: In total, 199 users of biological medicines responded to the survey. The respondents did not always know which product they were using, an originator or a biosimilar. This was more prominent among patients with biosimilars determined according to brand names. The more recently the biological medicine had been prescribed, the more likely a biosimilar was in use. Only about 40% of the respondents would enable pharmacies to substitute their biological medicine to a lower cost product. The most common obstacle to the idea of interchange in pharmacies was that the respondents wanted to keep the product the doctor had prescribed for them. In general, biosimilar users were more accepting towards possible interchange than originator users. Conclusion: Although the most recent treatments appear to be initiated with biosimilars, interchange in pharmacies could enable an efficient way to lower health care costs. However, guidance and awareness regarding biosimilars and biological medicines in general would improve patients' willingness towards the change, but also help pharmacists and prescribing doctors in their meaningful role.

Streamlining biosimilar development based on 20 years' experience.

INTRODUCTION: Biosimilar clinical programs could be streamlined by prudent application of improved methodologies and knowledge accumulated over the past 20 years. This review focuses on whether complex comparative efficacy trials are routinely needed and how to achieve a more tailored approach to biosimilar development. AREAS COVERED: Key learnings over the past 20 years are summarized. It is noted that a one size fits all approach to biosimilar development is not appropriate: biological medicines fall within a wide spectrum of complexity, with blurring at the interface between biological products and small molecules. The interrelationship between quality, potency, pharmacokinetics, pharmacology, immunogenicity, efficacy, and safety are reviewed. Current regulatory thinking is reviewed with a look into what future challenges lie ahead. EXPERT OPINION: To tailor regulatory requirements for marketing approval of biosimilars, it is proposed that a biosimilarity report be introduced. This report would integrate quality, pharmacology, immunogenicity, efficacy and safety findings and address how the clinical program could be tailored based on the totality of evidence.

How do patients value features of biological medicine in rheumatoid arthritis? A discrete choice experiment.

BACKGROUND: The aim of this study was to quantify the preference of the patients regarding biological DMARDs. RESEARCH DESIGN AND METHODS: Patients' preferences were assessed using a discrete choice experiment. Eighteen different surveys describing eight attributes were designed using experimental design methods. Each survey presented eight choice tasks with two options for patients to choose one. A conditional logit model was used to calculate relative importance and willingness to pay. Subgroup analysis was conducted to evaluate the effect of the patients' characteristic on their preferences. RESULTS: A total of 306 patients were included in the study. All attributes had significant effects on the patients' choices. The most important feature was the ability to preserve physical function. The least important feature was the route of administration. Surprisingly, the out-of-pocket cost was one of the last priorities for respondents. According to the relative importance calculations, 80% of the patients' preferences can be obtained by clinical attributes. Based on subgroup analysis, the most important patient characteristic that affected their choices was the monthly out-of-pocket history. CONCLUSIONS: Different features of treatment had different effects on the patients' preferences. Quantification of the impact of each attribute not only revealed their relative importance but also determined the trade-off rate among them.

Current situation and future development of the biopharmaceutical industry in China: A mixed-method study.

Introduction: The biomedical industry has grown significantly both globally and in China; however, there are still challenges. This study aimed at evaluating the biopharmaceutical sector of China, in terms of ability to innovate, current sales volume, investment, and R&D expenditure, as well as providing a case study detailing the progress and challenges of the industry in Shaanxi province. Method: A cross-sectional mixed-method study design was used to generate a comprehensive profile of the nature of biopharmaceutical innovation capacity and development in China by triangulating country-wide survey and interview data from Shaanxi province. Only biopharmaceutical companies that are currently marketing or conducting research and development were eligible for inclusion, and Shaanxi province was selected for conducting the interviews. Categorical and continuous variables were analyzed descriptively. Interviews were thematically analyzed by using NVivo version 12. Results: The analysis includes responses from 77 biopharmaceutical enterprises; the majority (36, 46.8%) are in Eastern China, followed by 26 (33.8%) in Central China. In 2018, the total sales of biological products amounted to 26.28 billion yuan, and in 2019, a slight increase was observed (30.34 billion); the amount doubled in 2020 to about 67.91 billion yuan. The top three biopharmaceutical products on sale in 2020 were Camrelizumab (5.14 billion yuan), human albumin (4.56 billion yuan), and human immunoglobulin for injection (3.78 billion yuan). Expenditure on R&D has also increased; it amounted to 1657.7 million yuan in 2018, which more than doubled in 2019 to 3572.1 million yuan and further increased to 5857.7 million yuan in 2020. Nonetheless, the progress is not uniform across all provinces, as shown from the results from Shaanxi province, because of lack of local government policies that will impact on the funding, incentives, and market share that motivate the producers. Conclusion: China's biopharmaceutical industry has expand significantly. The increase in sales indicates that there is an increase in demand for biologicals; moreover, R&D funding is increasing. These are key indicators that influence innovation and development. However, the sector's capacity to innovate and develop needs to be improved, particularly in the western region, where research and production are relatively weak.

Monoclonal antibodies and Fc-fusion protein biologic medicines: A multinational cross-sectional investigation of accessibility and affordability in Asia Pacific regions between 2010 and 2020.

Background: Monoclonal antibody (mAb) and Fc-fusion protein (FcP) are highly effective therapeutic biologics. We aimed to analyse consumption and expenditure trends in 14 Asia-Pacific countries/regions (APAC) and three benchmark countries (the UK, Canada, and the US). Methods: We analysed 440 mAb and FcP biological products using the IQVIA-MIDAS global sales database. For each year between 2010 and 2020 inclusive, we used standard units (SU) sold per 1000 population and manufacture level price (standardised in 2019 US dollars) to evaluate consumption (accessibility) and expenditure (affordability). Changes of consumption and expenditure were estimated using compound annual growth rate (CAGR). Correlations between consumption, country's economic and health performance indicators were measured using Spearman correlation coefficient. Findings: Between 2010 and 2020, CAGRs of consumption in each region ranged from 7% to 34% and the CAGRs of expenditure ranged from 9% to 31%. The median consumption of biologics was extremely low in lower-middle-income economies (0·29 SU/1000 population) compared with upper-middle-income economies (1·20), high-income economies (40·94) and benchmark countries (109·55), although the median CAGRs of biologics consumption in lower-middle-income economies (31%) was greater than upper-middle-income (14%), high-income economies (13%) and benchmark countries (9%). Consumption was correlated with GDP per capita [Spearman's rank correlation coefficient (r) = 0·75, p < 0·001], health expenditure as a percentage of total (r = 0·83, p < 0·001) and medical doctors' density (r = 0·85, p < 0·001). Interpretation: There have been significant increases in mAb and FcP biologics consumption and expenditure, however accessibility of biological medicines remains unequal and is largely correlated with country's income level. Funding: This research was funded by NHMRC Project Grant GNT1157506 and GNT1196900; Enhanced Start-up Fund for new academic staff and Internal Research Fund, Department of Medicine, LKS Faculty of Medicine, University of Hong Kong.

Exosomal therapy-a new frontier in regenerative medicine.

The recent advances in translational and nanomedicine have paved the way for developing the targeted drug delivery system at a greater pace among global researchers. On par with these technologies, exosomes act as a potential portal for cell-free drug delivery systems as these are bestowed with the native characteristics of the parent cell of origin. Exosomes, called extracellular vesicles (EcVs), are present in almost all cells, tissues, and body fluids. They help in intercellular signaling and maintains tissue homeostasis in the disease pathobiology. Researchers have characterized 9,769 proteins, 2,838 miRNAs, 3,408 mRNAs, and 1,116 lipids being present in exosomal cargo. The separation of exosomes from cells, tissues, and body fluids follow different patterned kinetics. Exosomes interact with the recipient cells through their surface receptor molecules and ligands and internalize within recipient cells through micropinocytosis and phagocytosis. Advancing technologies in regenerative medicine have facilitated the researchers to isolate exosomes from mesenchymal stem cells (MSCs) as these cells are blessed with supreme regenerative potentiality in targeting a disease. Exosomal cargo is a key player in establishing the diagnosis and executing therapeutic role whilst regulating a disease process. Various in vitro studies have exhibited the safety, efficacy, and therapeutic potentiality of exosomes in various cancers, neurodegenerative, cardiovascular, and orthopedic diseases. This article throws light on the composition, therapeutic role, and regulatory potentials of exosomes with the widening of the horizon in the field of regenerative medicine.

Manufacturing biological medicines on demand: Safety and efficacy of granulocyte colony-stimulating factor in a mouse model of total body irradiation.

Protein therapeutics, also known as biologics, are currently manufactured at centralized facilities according to rigorous protocols. The manufacturing process takes months and the delivery of the biological products needs a cold chain. This makes it less responsive to rapid changes in demand. Here, we report on technology application for on-demand biologics manufacturing (Bio-MOD) that can produce safe and effective biologics from cell-free systems at the point of care without the current challenges of long-term storage and cold-chain delivery. The objective of the current study is to establish proof-of-concept safety and efficacy of Bio-MOD-manufactured granulocyte colony-stimulating factor (G-CSF) in a mouse model of total body irradiation at a dose estimated to induce 30% lethality within the first 30 days postexposure. To illustrate on-demand Bio-MOD production feasibility, histidine-tagged G-CSF was manufactured daily under good manufacturing practice-like conditions prior to administration over a 16-day period. Bio-MOD-manufactured G-CSF improved 30-day survival when compared with saline alone (p = .073). In addition to accelerating recovery from neutropenia, the platelet and hemoglobin nadirs were significantly higher in G-CSF-treated animals compared with saline-treated animals (p < .05). The results of this study demonstrate the feasibility of consistently manufacturing safe and effective on-demand biologics suitable for real-time release.

The Market of Biopharmaceutical Medicines: A Snapshot of a Diverse Industrial Landscape.

Background: Biopharmaceutical medicines represent a growing share of the global pharmaceutical market, and with many of these biopharmaceutical products facing loss of exclusivity rights, also biosimilars may now enter the biopharmaceutical market. Objectives: This study aims to identify and document which investment and development strategies are adopted by industrial players in the global biopharmaceutical market. Methods: A descriptive analysis was undertaken of the investment and development strategies of the top 25 pharmaceutical companies according to 2015 worldwide prescription drug sales. Strategies were documented by collecting data on manufacturing plans, development programs, acquisition and collaboration agreements, the portfolio and pipeline of biosimilar, originator and next-generation biopharmaceutical products. Data were extracted from publicly available sources. Results: Various investment and development strategies can be identified in the global biopharmaceutical market: (a) development of originator biopharmaceuticals, (b) investment in biotechnology, (c) development of next-generation biopharmaceuticals, (d) development of biosimilars, (e) investment in emerging countries, and (f) collaboration between companies. In the top 25 pharmaceutical companies almost every company invests in originator biopharmaceuticals and in biotechnology in general, but only half of them develops next-generation biopharmaceuticals. Furthermore, only half of them invest in development of biosimilars. The companies' biosimilar pipeline is mainly focused on development of biosimilar monoclonal antibodies and to some extent on biosimilar insulins. A common strategy is collaboration between companies and investment in emerging countries. Conclusions: A snapshot of investment and development strategies used by industrial players in the global biopharmaceutical market shows that all top 25 pharmaceutical companies are engaged in the biopharmaceutical market and that this industrial landscape is diverse. Companies do not focus on a single strategy, but are involved in multiple investment and development strategies. A common strategy to market biopharmaceuticals is collaboration between companies. These collaborations can as well be used to gain access in regions the company has less experience with. With patents expiring for some of the highest selling monoclonal antibodies, this snapshot highlights the interest of companies to invest in the development of these molecules and/or enter into collaborations to create access to these molecules.

The use of rat spinal reflexes to quantify injection pain.

Pain caused by subcutaneous injections is unpleasant, which may limit patient compliance. The objective of this study was to use spinal reflexes to quantify subcutaneous injection pain. Spinal reflexes were measured using an electromyogram (EMG) test. The effects of injection volume, pH and osmotic pressure were investigated. The EMG responses increased with injection volume and the acidity of the solution but did not depend on the osmotic pressure of the solution. The EMG responses differed for subcutaneously injected sodium chloride and glucose over the same range of osmotic pressures. Pain caused by the subcutaneous injections was unrelated to the osmotic ratio up to approximately 5. The injection pain caused by therapeutic protein solutions was also evaluated. We compared the EMG responses of the adalimumab and etanercept, as the injection of adalimumab is more painful than that of etanercept in humans. The EMG magnitude for adalimumab was twice that induced by etanercept as observed for the EMG tests performed in rats. Therapeutic proteins account for an increasingly large proportion of pharmaceutical drugs. When a high dose of therapeutic proteins is required, the protein solution must often be highly concentrated to reduce the injection volume. For patient comfort, it is critical to reduce injection pain. The EMG test reported here allows subcutaneous injection pain to be quantified and may be useful for optimizing drug formulations.

Efecto modulador de la ozonoterapia sobre la actividad del sistema inmune / Modulator effect of ozone therapy over immune system activity

El empleo de la medicina biológica ha permitido aplicar terapias sistémicas beneficiosas donde el cuerpo es tratado como un todo. La ozonoterapia es una técnica interesante en el campo de aplicación de la medicina biológica; es un proceder terapéutico, seguro, natural y factible, con resultados alentadores en el tratamiento de enfermedades inmunológicas, por el impacto social y económico que se genera tras su aplicación. Existen evidencias experimentales que aseveran esta afirmación. En este artículo se describen las propiedades inmunomoduladoras de la ozonoterapia, al caracterizar los efectos biológicos del ozono sobre las células del sistema inmune, mediadores solubles y otros tipos celulares

The employment of biological medicine has allowed the application of beneficial and systemic therapies where the body is treated as a whole. The ozone therapy is a modality of the biological medicine, it is a natural therapeutical procedure that has represented an extremely safe medical therapy, free from side effects, an effective and feasible method in the field of treatment of immunological diseases, with encouraging results for the social and economic impact that is generated after its application. There are experimental evidences that assert this statement. We hereby describe the immunomodulatory property of ozone therapy, the biological effects of the ozone on the cells of the immune system cells, other cellular types and different immune mediators