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European Journal of Pharmacology Apr 2023Pharmacological treatments available for substance use disorder (SUD) focus on pharmacodynamics, agonizing or antagonizing the drug of abuse (DOA) on receptor level.... (Review)
Review
BACKGROUND AND OBJECTIVES
Pharmacological treatments available for substance use disorder (SUD) focus on pharmacodynamics, agonizing or antagonizing the drug of abuse (DOA) on receptor level. Drawbacks of this approach include the reliance on long-term patient compliance, on-target off-site effects, perpetuation of addiction and unavailability for many DOAs. Newer, pharmacokinetic approaches are needed that restrict DOA's access to the brain or disrupt DOA-instated brain changes maintaining addiction. Biotechnology might be able to provide the right biopharmaceutical tools to deliver a fine-tuned solution with less side effects compared to currently available treatments.
METHODS
This review examines the available literature on biopharmaceuticals developed to treat SUD.
RESULTS
Active and passive immunization, metabolic enhancers that augment DOA metabolism and clearance, as well as genetic/epigenetic modulation are promising next generation SUD treatments. Active immunization relies on production of antidrug antibodies by means of vaccination, while passive immunization constitutes of exogenous administration of such antibodies. Metabolic enhancers include drug-specific metabolizing enzymes that can be administered or secreted by modified skin grafts, as well as catalytic antibodies that hasten DOA metabolism. Nanotechnological advances can also allow for brain delivery of siRNAs, mRNAs or DNA in order to modulate central, common in all addictions, genetic or epigenetic targets attenuating drug seeking behavior and reversing drug-induced brain changes.
CONCLUSIONS
and Scientific Significance: Biopharmaceuticals can in the future complement or even replace traditional pharmacodynamics approaches in SUD treatment. While passive and active immunization biopharmaceuticals have entered human clinical trials, metabolic enhancers and genetic approaches are at the preclinical level.
Topics: Humans; Biological Products; Substance-Related Disorders; Antibodies; Immunization, Passive; Behavior, Addictive; Illicit Drugs
PubMed: 36775113
DOI: 10.1016/j.ejphar.2023.175587 -
Journal of Medical Economics 2023In the US, RSV imposes significant burdens on infants, households, and the health system. Yet the only licensed immunization is accessible to only certain risk groups...
In the US, RSV imposes significant burdens on infants, households, and the health system. Yet the only licensed immunization is accessible to only certain risk groups comprising 2% of the infant population, leaving the remaining 98% unprotected. An effective immunization for all infants is a significant public health priority. One possible solution is the FDA-approved monoclonal antibody nirsevimab, which recent evidence suggests is safe and effective in preventing RSV in all infants, and which is currently being considered for inclusion in the pediatric immunization schedule and the federal Vaccines for Children (VFC) program. But the question arises whether immunization products like nirsevimab ought to be eligible for the VFC, which nominally and traditionally centers on vaccines providing immunity. Addressing this is urgent because VFC inclusion will be decided on imminently. I argue there are strong policy grounds, i.e., reasons grounded in the ultimate health system goals of maximizing population health or social welfare subject to resource constraints, not to exclude passive immunization from VFC eligibility. Active and passive immunizations both provide adaptive immunity and can therefore produce qualitatively similar effects on risks of infection, disease, and transmission; on disease severity and duration; and on health, welfare, and health resource use. The distinction between active and passive immunization does not intrinsically matter since what matters for the attainment of health system goals is the extent of immunity conferred, not whether immunity is active or passive. Nor can passivity be considered a useful proxy for conferring a lesser extent of immunity, since no such proxy is needed (existing valuation methods can cope with variations in product attributes), and it is a poor proxy (passive immunizations can be better for individuals with impaired immune systems and can have comparable effectiveness durations and economic value as vaccines).
Topics: Infant; Child; Humans; Antibodies, Monoclonal; Respiratory Syncytial Virus Infections; Immunization; Vaccination; Immunization, Passive
PubMed: 37498791
DOI: 10.1080/13696998.2023.2242169 -
The European Respiratory Journal Feb 2022https://bit.ly/3DGyz6t
https://bit.ly/3DGyz6t
Topics: Antibodies, Viral; COVID-19; Humans; Immunization, Passive; SARS-CoV-2; COVID-19 Serotherapy
PubMed: 34531275
DOI: 10.1183/13993003.02076-2021 -
Expert Opinion on Biological Therapy Oct 2016Outcome for glioma (GBM) remains dismal despite advances in therapeutic interventions including chemotherapy, radiotherapy and surgical resection. The overall survival... (Review)
Review
INTRODUCTION
Outcome for glioma (GBM) remains dismal despite advances in therapeutic interventions including chemotherapy, radiotherapy and surgical resection. The overall survival benefit observed with immunotherapies in cancers such as melanoma and prostate cancer has fuelled research into evaluating immunotherapies for GBM.
AREAS COVERED
Preclinical studies have brought a wealth of information for improving the prognosis of GBM and multiple clinical studies are evaluating a wide array of immunotherapies for GBM patients. This review highlights advances in the development of immunotherapeutic approaches. We discuss the strategies and outcomes of active and passive immunotherapies for GBM including vaccination strategies, gene therapy, check point blockade and adoptive T cell therapies. We also focus on immunoediting and tumor neoantigens that can impact the efficacy of immunotherapies.
EXPERT OPINION
Encouraging results have been observed with immunotherapeutic strategies; some clinical trials are reaching phase III. Significant progress has been made in unraveling the molecular and genetic heterogeneity of GBM and its implications to disease prognosis. There is now consensus related to the critical need to incorporate tumor heterogeneity into the design of therapeutic approaches. Recent data also indicates that an efficacious treatment strategy will need to be combinatorial and personalized to the tumor genetic signature.
Topics: Animals; Forecasting; Genetic Therapy; Glioblastoma; Glioma; Humans; Immunization, Passive; Immunotherapy; Prognosis; Treatment Outcome; Tumor Microenvironment
PubMed: 27411023
DOI: 10.1080/14712598.2016.1212012 -
Microbiology Spectrum Apr 2015Antibodies and passive antibody therapy in the treatment of infectious diseases is the story of a treatment concept which dates back more than 120 years, to the 1890s,... (Review)
Review
Antibodies and passive antibody therapy in the treatment of infectious diseases is the story of a treatment concept which dates back more than 120 years, to the 1890s, when the use of serum from immunized animals provided the first effective treatment options against infections with Clostridium tetani and Corynebacterium diphtheriae. However, after the discovery of penicillin by Fleming in 1928, and the subsequent introduction of the much cheaper and safer antibiotics in the 1930s, serum therapy was largely abandoned. However, the broad and general use of antibiotics in human and veterinary medicine has resulted in the development of multi-resistant strains of bacteria with limited to no response to existing treatments and the need for alternative treatment options. The combined specificity and flexibility of antibody-based treatments makes them very valuable tools for designing specific antibody treatments to infectious agents. These attributes have already caused a revolution in new antibody-based treatments in oncology and inflammatory diseases, with many approved products. However, only one monoclonal antibody, palivizumab, for the prevention and treatment of respiratory syncytial virus, is approved for infectious diseases. The high cost of monoclonal antibody therapies, the need for parallel development of diagnostics, and the relatively small markets are major barriers for their development in the presence of cheap antibiotics. It is time to take a new and revised look into the future to find appropriate niches in infectious diseases where new antibody-based treatments or combinations with existing antibiotics, could prove their value and serve as stepping stones for broader acceptance of the potential for and value of these treatments.
Topics: Animals; Antibodies; Communicable Diseases; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Immunization, Passive
PubMed: 26104697
DOI: 10.1128/microbiolspec.AID-0026-2014 -
Transfusion Medicine (Oxford, England) Feb 2023The COVID-19 pandemic severely tested the resilience of the US blood supply with wild fluctuations in blood donation and utilisation rates as community donation... (Review)
Review
The COVID-19 pandemic severely tested the resilience of the US blood supply with wild fluctuations in blood donation and utilisation rates as community donation opportunities ebbed and hospitals post-poned elective surgery. Key stakeholders in transfusion services, blood centres, supply chains and manufacturers reviewed their experiences during the SARS-CoV-2 pandemic as well as available literature to describe successes, opportunities for improvement and lessons learned. The blood community found itself in uncharted territory responding to restriction of its access to donors (approximately 20% decrease) and some supplies; environmental adjustments to address staff and donor concerns about coronavirus transmission; and the development of a new product (COVID-19 convalescent plasma [CCP]). In assuring that the needs of the patients were paramount, the donation process was safe, that clinicians had access to CCP, and vendor relationships aligned, the blood banking community relearned its primary focus: improving patient outcomes.
Topics: Humans; United States; COVID-19; SARS-CoV-2; Pandemics; COVID-19 Serotherapy; Blood Donors; Immunization, Passive
PubMed: 35918741
DOI: 10.1111/tme.12896 -
Molecular Therapy : the Journal of the... Apr 2019First attempts to use exogenous mRNA for protein expression in vivo were made more than 25 years ago. However, widespread appreciation of in vitro transcribed mRNA as... (Review)
Review
First attempts to use exogenous mRNA for protein expression in vivo were made more than 25 years ago. However, widespread appreciation of in vitro transcribed mRNA as a powerful technology for supplying therapeutic proteins to the body has evolved only during the past few years. Various approaches to turning mRNA into a potent therapeutic have been developed. All of them share utilization of specifically designed, rather than endogenous, sequences and thorough purification protocols. Apart from this, there are two fundamental philosophies, one promoting the use of chemically modified nucleotides, the other advocating restriction to unmodified building blocks. Meanwhile, both strategies have received broad support by successful mRNA-based protein treatments in animal models. For such in vivo use, specifically optimized mRNA had to be combined with potent formulations to enable efficient in vivo delivery. The present review analyzes the applicability of mRNA technology to antibody therapy in all main fields: antitoxins, infectious diseases, and oncology.
Topics: Animals; Antibodies, Monoclonal; Communicable Diseases; Drug Compounding; Drug Delivery Systems; Humans; Immunization, Passive; Lipids; Nanoparticles; Neoplasms; RNA, Messenger; Toxins, Biological
PubMed: 30885573
DOI: 10.1016/j.ymthe.2019.03.002 -
Animal Health Research Reviews Dec 2015Passive immunization with pathogen-specific egg yolk antibodies (IgY) is emerging as a potential alternative to antibiotics for the treatment and prevention of various... (Review)
Review
Passive immunization with pathogen-specific egg yolk antibodies (IgY) is emerging as a potential alternative to antibiotics for the treatment and prevention of various human and animal diseases. Laying hens are an excellent source of high-quality polyclonal antibodies, which can be collected noninvasively from egg yolks. The use of IgY offers several advantages in that it is environmentally friendly, nontoxic, and reduces the numbers of animals required for antibody production. This paper reviews the use of IgY antibodies in the treatment and prevention of enteric pathogen infections in poultry. Brief descriptions of the production, structure, and properties of IgY are also presented. Some limitations of the technology and future perspectives are discussed.
Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Chickens; Egg Yolk; Humans; Immunization, Passive; Immunoglobulins; Poultry; Poultry Diseases
PubMed: 26568433
DOI: 10.1017/S1466252315000195 -
Journal of Biological Regulators and... 2021Infection with SARS-CoV2 leads to COVID-19, the severity of which derives from the host’s immune response, especially the release of a storm of pro-inflammatory...
Infection with SARS-CoV2 leads to COVID-19, the severity of which derives from the host’s immune response, especially the release of a storm of pro-inflammatory cytokines. This coronavirus infects by first binding to the ectoenzyme Angiotensin Converting Enzyme 2 (ACE2), a serine protease acting as the receptor, while another serine protease is necessary for priming the viral spike “S” protein required for entering the cells. Repurposing existing drugs for potential anti-coronavirus activity have failed. As a result, there were intense efforts to rapidly produce ways of providing prophylactic active immunization (vaccines) or abortive passive (convalescent plasma or monoclonal antibodies) neutralizing antibodies. The availability of vaccines for COVID-19 have been largely successful, but many questions still remain unanswered. In spite of the original enthusiasm, clinical studies using convalescent serum or monoclonal antibodies have shown limited benefit. Moreover, the emergence of Long-COVID syndrome in most infected patients necessitates the development of treatment approaches that may prevent viral entry by blocking both serine proteases involved, as with a liposomal blend of the natural flavonoids luteolin and quercetin.
Topics: Antibodies, Viral; COVID-19; COVID-19 Vaccines; Humans; Immunization, Passive; Peptidyl-Dipeptidase A; RNA, Viral; SARS-CoV-2; Spike Glycoprotein, Coronavirus; COVID-19 Serotherapy
PubMed: 33896155
DOI: 10.23812/Theo_edit -
MBio Feb 2017A century ago, Emil von Behring passed away. He was the first to be honored by the Nobel Prize for Medicine in 1901 for the successful therapy of diphtheria and tetanus,...
A century ago, Emil von Behring passed away. He was the first to be honored by the Nobel Prize for Medicine in 1901 for the successful therapy of diphtheria and tetanus, which he had developed from the bench to the bed. He also contributed to the foundation of immunology, since his therapy was based on passive immunization with specific antisera. Being an ambitious character, he did not shy away from friction with his colleagues Paul Ehrlich and Elias Metchnikoff and his mentor, Robert Koch. Behring was not only an excellent translational researcher but also a successful entrepreneur and early proponent of public-private partnerships.
Topics: Antibodies; Diphtheria; History, 19th Century; History, 20th Century; Humans; Immunization, Passive; Immunotherapy; Phagocytes; Tetanus
PubMed: 28246359
DOI: 10.1128/mBio.00117-17