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This comprehensive review provides a critical synthesis of the transformative roles of monoclonal antibodies and tyrosine kinase inhibitors in modern oncology, as reflected in the most recent National Comprehensive Cancer Network guidelines evaluated during the defined 2025 data-collection window.
Methods
From nearly 200 recommended targeted agents, we focus on those with the highest clinical impact, selected for their frequency of use, paradigm-shifting influence and relevance across multiple tumour types. For each therapy, the mechanism of action, biomarker-driven applications, tumour-agnostic approvals and landmark clinical trials are discussed.
Results
This study highlights the evolution from empiric chemotherapy to precision medicine and critically examines resistance mechanisms, safety, real-world access disparities and the integration of molecular diagnostics. It also discusses combination strategies, adaptive trial designs and next-generation modalities.
Conclusions
This work provides clinicians and researchers with a concise reference for navigating the rapidly expanding field of precision oncology therapeutics.
Dementia affects approximately 6–13% of adults aged 65 years and older, with Alzheimer’s disease accounting for most cases. Established symptomatic therapies, including acetylcholinesterase inhibitors and memantine, provide limited benefit and do not modify disease progression. Multiple monoclonal antibodies (mABs) targeting different amyloid-β species have been developed as potential disease-modifying therapies; because some agents have entered clinical use whereas others remain investigational, a continuously updated synthesis of their efficacy and safety is needed.
Aims
To evaluate the efficacy and safety of all anti-amyloid mABs for adults with Alzheimer’s disease, using a living systematic review and meta-analysis.
Method
We will conduct a living systematic review and meta-analysis in accordance with the Cochrane Handbook, Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 and the PRISMA extension for living systematic reviews. Randomised controlled trials comparing any approved or investigational anti-amyloid mAB with placebo, standard care or active comparators will be included. Searches of Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform will be updated every 6 months. Meta-analyses will be conducted separately for each antibody molecule using random-effects models. Critical outcomes include global clinical change and disease severity, cognitive abilities, functional ability and dependency, and safety (serious adverse events, treatment discontinuation and amyloid-related imaging abnormalities). Important outcomes include neuropsychiatric symptoms, quality of life and health system outcomes. Certainty of evidence will be assessed using the methodology Grading of Recommendations, Assessment, Development and Evaluation.
Results
This article describes a protocol; therefore, no review findings are available at this stage.
Conclusions
This living systematic review will provide an up-to-date synthesis of the benefits and harms of anti-amyloid monoclonal antibodies to inform clinical decision-making and health-system planning in Alzheimer’s disease.
Multiple sclerosis (MS) is characterized by focal inflammatory activity in the central nervous system and a diffuse, compartmentalized inflammation that is the primary driver of neuroaxonal damage and worsening disability. It is now recognized that higher-efficacy disease-modifying therapies (HE-DMT) are often required to treat the complex neuropathological changes that occur during the disease course and improve long-term outcomes. The optimal use of HE-DMTs in practice was addressed by a Canadian panel of 12 MS experts who used the Delphi method to develop 27 consensus recommendations. The HE-DMTs that were considered were the monoclonal antibodies (natalizumab, ocrelizumab, ofatumumab) and the immune reconstitution agents (alemtuzumab, cladribine). The issues addressed included defining aggressive/severe disease, patient selection of the most appropriate candidates for HE-DMTs, baseline investigations and efficacy monitoring, defining suboptimal treatment response, use of serum neurofilament-light chain in evaluating treatment response, safety monitoring, aging and immunosenescence and when to consider de-escalating or discontinuing treatment. The goals of the consensus recommendations were to provide guidelines to clinicians on their use of HE-DMTs in practice and to improve long-term outcomes in persons with MS.
Flow cytometry relies on the use of fluorochrome-conjugated antibodies, most of them identified and produced after the discovery of the technology allowing to generate large amounts of monoclonal antibodies. Hence, nearly all these reagents are named after the cluster of differentiation (CD) number that was given to newly discovered molecules they recognize, many of them having no other name. Although some CDs have become very popular and well known, others are less familiar. This chapter provides a guide to recover the characteristics of surface or cytoplasmic antigens explored with the CDs most frequently used in the field of haematological malignancies.
Coronavirus disease-2019 precipitated the rapid deployment of novel therapeutics, which led to operational and logistical challenges for healthcare organizations. Four health systems participated in a qualitative study to abstract lessons learned, challenges, and promising practices from implementing neutralizing monoclonal antibody (nMAb) treatment programs. Lessons are summarized under three themes that serve as critical building blocks for health systems to rapidly deploy novel therapeutics during a pandemic: (1) clinical workflows, (2) data infrastructure and platforms, and (3) governance and policy. Health systems must be sufficiently agile to quickly scale programs and resources in times of uncertainty. Real-time monitoring of programs, policies, and processes can help support better planning and improve program effectiveness. The lessons and promising practices shared in this study can be applied by health systems for distribution of novel therapeutics beyond nMAbs and toward future pandemics and public health emergencies.
This chapter reviews current options for pharmacological interventions for treating dementia and MCI. For the last 20 years, ACHe inhibitors have been the main option for symptomatic treatment of dementia. The evidence base for their effectiveness is considered. More recent developments are reviewed for pharmacological interventions intended to be disease-modifying. These aim to remove beta amyloid protein, which is the hallmark of Alzheimer’s disease, with the aim of halting the disease’s progress. This is an emerging field, with an evidence base which is still developing, but represents an exciting development.
Like Alzheimer’s disease, Parkinson’s disease is a progressive, neurodegenerative disorder that involves deposits of an abnormal protein in the brain. In Alzheimer’s disease, these abnormal proteins are extracellular beta-amyloid and intraneuronal, hyperphosphorylated tau. In Parkinson’s disease, the neuropathological findings are protein deposits of aggregated alpha-synuclein found primarily within neurons in a part of the brainstem called the substantia nigra but in other locations as well. These clumps of alpha-synuclein are called Lewy bodies.
In the August 4, 2022 issue of the New England Journal of Medicine, we have reports of two phase 2 human trials of monoclonal antibodies directed at alpha-synuclein in subjects with early-stage Parkinson’s disease, prasinezumab and cinpanemab.
Multi-level dissemination strategies are needed to increase equitable access to effective treatment for high-risk outpatients with COVID-19, particularly among patients from disproportionately affected communities. Yet assessing population-level impact of such strategies can be challenging.
Methods:
In collaboration with key contributors in Colorado, we conducted a retrospective cohort study to evaluate a multi-level dissemination strategy for neutralizing monoclonal antibody (mAb) treatment. Real-world data included county-level, de-identified output from a statewide mAb referral registry linked with publicly available epidemiological data. Outcomes included weekly number of mAb referrals, unique referring clinicians, and COVID-19 hospitalization rates. We assessed weekly changes in outcomes after dissemination strategies launched in July 2021.
Results:
Overall, mAb referrals increased from a weekly average of 3.0 to 15.5, with an increase of 1.3 to 42.1 additional referrals per county in each post-period week (p < .05). Number of referring clinicians increased from a weekly average of 2.2 to 9.7, with an additional 1.5 to 22.2 unique referring clinicians observed per county per week beginning 5 weeks post-launch (p < .001). Larger effects were observed in communities specifically prioritized by the dissemination strategies. There were no observed differences in COVID-19 hospitalization rates between counties with and without mAb treatment sites.
Conclusion:
Real-world data can be used to estimate population impact of multi-level dissemination strategies. The launch of these strategies corresponded with increases in mAb referrals, but no apparent population-level effects on hospitalization outcomes. Strengths of this analytic approach include pragmatism and efficiency, whereas limitations include inability to control for other contemporaneous trends.
On June 18, 2023, the U.S. Supreme Court in the matter of Amgen, Inc. et al. v. Sanofi, et al.1 unanimously upheld the 2021 decision of the U.S. Court of Appeals for the Federal Circuit,2 striking down as overbroad Amgen’s patent claim to an entire functional genus of monoclonal antibodies. Amgen’s patent claims were not limited to antibody structure or antibody amino acid sequences. This is significant because Amgen’s patent claims did have amino acid sequences, but they were directed to the epitope.
Nearly 3 years after its detection, the coronavirus disease 2019 (COVID-19) which is caused by severe acute respiratory syndrome CoV-2, is still a life-threatening global pandemic that has contributed to a high progression and mortality rate across the globe. This imposes the need for scientific research efforts in order to hold intense interest directed towards such exploration, for the development and optimization of different interventions to the COVID-19 infection. This commentary summarizes the potential clinical benefits for the recently authorized immunotherapy combination of Tixagevimab and Cilgavimab monoclonal antibodies for the prevention and treatment of COVID-19.
Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS) that often progresses to severe disability. Previous studies have highlighted the role of T cells in disease pathophysiology; however, the success of B-cell-targeted therapies has led to an increased interest in how B cells contribute to disease immunopathology. In this review, we summarize evidence of B-cell involvement in MS disease mechanisms, starting with pathology and moving on to review aspects of B cell immunobiology potentially relevant to MS. We describe current theories of critical B cell contributions to the inflammatory CNS milieu in MS, namely (i) production of autoantibodies, (ii) antigen presentation, (iii) production of proinflammatory cytokines (bystander activation), and (iv) EBV involvement. In the second part of the review, we summarize medications that have targeted B cells in patients with MS and their current position in the therapeutic armamentarium based on clinical trials and real-world data. Covered therapeutic strategies include the targeting of surface molecules such as CD20 (rituximab, ocrelizumab, ofatumumab, ublituximab) and CD19 (inebilizumab), and molecules necessary for B-cell activation such as B cell activating factor (BAFF) (belimumab) and Bruton’s Tyrosine Kinase (BTK) (evobrutinib). We finally discuss the use of B-cell-targeted therapeutics in pregnancy.
Over the past decades, immunotherapy treatments have been a revolution to many chronic diseases with encouraging results in clinical outcomes and quality of life. The use of monoclonal antibodies has yielded a great variability in terms of clinical efficacy and tolerability although it’s believed the incidence of psychotic symptoms is low (0,1-0,4%).
Objectives
To review the effects of monoclonal antibodies on psychosis.
Methods
Review of literature using PubMed database. A total of 16 studies were included.
Results
The targeted molecules by monoclonal antibodies may determine the risk of psychosis. While those who target TNF-alfa seem to have a reduced risk of psychosis (such as Infliximab, Adalimumab, Certolizumab and Golimumab), monoclonal antibodies who modulate lymphocytes may have a greater risk of psychosis namely Natalizumab, Belimumab, Basiliximab and Daclizumab, which seems to correlate to evidence of alterations in lymphocyte subsets in groups of patients with first psychotic episode and schizophrenia. Some seem to have positive correlation with psychosis namely monoclonal antibodies who have a supressing effect on the immune system, especially those who target adaptative immunity and those who are used in autoimmune diseases (vs oncologic conditions). It is unknown if delusions prevail over hallucinations or vice-versa. Despite the paucity of evidence, these findings corroborate the variability regarding the psychiatric effects of immunotherapy.
Conclusions
The available literature reports a low prevalence of psychotic symptoms associated with the use of monoclonal antibodies but it highlights the importance in knowing the immune mechanisms involved in psychotic disorders. Greater research is needed to correctly assess that risk.
In the chapter “The Biotechnology Sector – Therapeutics”, the author covers a wide range of topics summarizing the significant role that the formation and growth of the biotechnology sector has played in the entire biopharmaceutical industry. The chapter begins with a bit of history, from the earliest days of how genetic engineering gave birth to this sector, and takes the reader through an overview of biotechnology as it exists today and how the growing innovation in science over the years has been able to both drive the sector and have a tremendous impact on healthcare overall. There is a particular focus on describing various types of innovation which have played a huge role in driving product development in the broader biopharmaceutical industry. Later in the chapter, there is a focus on many of the business aspects of the sector, as drug development in biotechnology requires enormous amounts of capital for success. The author outlines many of the key issues related to different business and financing models that we see across the sector, in addition to the unique management issues in small biotechnology companies. There is significant description and explanation of the symbiotic relationship between the larger pharmaceutical companies and smaller biotechnology start-ups with a focus on how they help each other to bring transformative medicines to patients. The chapter concludes with a discussion about international and regulatory aspects impacting the sector. Overall the author tells the story of the birth and growth of this exciting sector, and its impact on patients and drug development over the last forty years, well substantiated with current data to build the case for how biotechnology today plays a major role in driving one of the most important and exciting technological industries of our time.
Migraine varies in its frequency, severity, and impact; treatment should consider these variations and the patient’s needs and goals. Migraine pharmacologic treatment may be acute (abortive) or preventive (prophylactic), and patients often require both. New medication devices are available or in development, including an intracutaneous, microneedle system of zolmitriptan and sumatriptan, and breath-powered powder sumatriptan intranasal treatment. Lasmiditan, a 5-HT1F receptor agonist, is in development for acute treatment, as are small molecule calcitonin gene-related peptide (CGRP) receptor antagonists (Gepants) for acute and preventive treatment. Antibodies to CGRP and its receptor are being developed for migraine prevention. All 4 treatments are effective and have, as of yet, no safety concerns.
Trichinella spiralis is an intracellular parasitic nematode of mammalian skeletal muscle, causing a serious zoonotic disease in humans and showing a high economic impact mainly in pig breeding. Serine proteinases of T. spiralis play important roles in the host–parasite interactions mediating host invasion. In this study, we have focused on newborn larvae (NBL-1), the first identified serine proteinase from the NBL stage of T. spiralis. Five monoclonal antibodies (mAbs) directed against the C-terminal part of NBL1, were produced. These mAbs were IgG1κ isotype and specifically recognized as a common motif of 10 amino acids (PSSGSRPTYP). Selected mAbs were further characterized using antigens from various developmental stages of T. spiralis. Western blot revealed that selected mAbs reacted with the native NBL1 at Mr 50 kDa in the adult and NBL mixed antigens and NBL stage alone. Indirect immunofluorescence analysis revealed that selected mAbs intensely stained only the embryos within the gravid females and the NBL. Thus, the produced mAbs are useful tools for the characterization of NBL1 as a major antigen of Trichinella involved in the invasion of the host but also for the development of new serological tests with an early detection of T. spiralis infection.
Tritrichomonas foetus is a protist that causes bovine trichomoniasis and presents a well-developed Golgi. There are very few studies concerning the Golgi in trichomonads. In this work, monoclonal antibodies were raised against Golgi of T. foetus and used as a tool on morphologic and biochemical studies of this organelle. Among the antibodies produced, one was named mAb anti-Golgi 20.3, which recognized specifically the Golgi complex by fluorescence and electron microscopy. By immunoblotting this antibody recognized two proteins with 60 and 66 kDa that were identified as putative beta-tubulin and adenosine triphosphatase, respectively. The mAb 20.3 also recognized the Golgi complex of the Trichomonas vaginalis, a human parasite. In addition, the nucleotide coding sequences of these proteins were identified and included in the T. foetus database, and the 3D structure of the proteins was predicted. In conclusion, this study indicated: (1) adenosine triphosphatase is present in the Golgi, (2) ATPase is conserved between T. foetus and T. vaginalis, (3) there is new information concerning the nucleic acid sequences and protein structures of adenosine triphosphatase and beta-tubulin from T. foetus and (4) the mAb anti-Golgi 20.3 is a good Golgi marker and can be used in future studies.
The factors that characterize Acanthamoeba strains as harmless or potentially pathogenic have not been elucidated. Analysing the in vitro and in vivo parameters of Acanthamoeba samples, including heat tolerance at temperatures close to that of the human body, cytopathic effects, and their ability to cause infections in animals, has been proposed to identify their pathogenic potential. Another promising criterion for differentiating strains is the analysis of their biochemical and immunochemical properties. In this study, a comparative evaluation between clinical and environmental Acanthamoeba isolates was performed on the basis of physiological, morphological, and immunochemical criteria. Crude antigens were used to characterize the protein profiles by electrophoresis and immunize mice to produce polyclonal and monoclonal antibodies. The antibodies were characterized using ELISA, Western blotting, and immunofluorescence techniques. The results obtained with polyclonal antibodies suggest the presence of specific proteins for each studied isolate and co-reactive immunochemical profiles among conserved components. Ten monoclonal antibody clones were obtained; mAb3 recognized 3 out of 4 samples studied. The results of this study may help standardize criteria for identifying and characterizing Acanthamoeba strains. Taken together, our results support the view that a set of features may help differentiate Acanthamoeba species and isolates.
In vitro, two different classes of antibodies are recognized according to the assay used to identify them: binding antibodies (BAbs) and neutralizing antibodies (NAbs). There is emerging agreement that NAbs are correlated with reduced therapeutic efficacy of IFNβ. None of the pivotal trials in relapsing-remitting multiple sclerosis (MS) showed an effect of NAbs on disease progression. Among the therapeutic monoclonal antibodies natalizumab, alemtuzumab, and daclizumab are humanized monoclonal antibodies, whereas rituximab is a mouse-human chimeric antibody. NAbs are associated with reduction of the therapeutic effect of IFNβ, and patients with persistent high titers of NAbs should be switched to an alternative therapy. Patients with low or intermediate titers should have their IFN bioactivity measured with an in vivo mRNA MxA induction test. Patients with repeated abrogation of the mRNA MxA response to IFN injections should be switched to another therapy.
This chapter outlines the events involved in the adaptive and innate immune responses to a transplant and the subsequent mechanisms of rejection, concluding with current clinical and experimental strategies to protect transplants from immune-mediated damage. The recognition of foreign antigens by naive host (recipient) T cells is a principal step in the rejection process. Allorecognition in the presence of costimulation results in the activation and expansion of T-cells that recognize the mismatched donor alloantigens. Immunosuppressive therapy can be credited with the vast improvements in transplant survival. The chapter explores the underlying mechanisms of action in relation to the immunobiology. Newer monoclonal antibodies include alemtuzumab, rituximab, basiliximab, and daclizumab, which target specific T-cell surface proteins. The advances in immunosuppression have improved short- and medium-term graft survival rates and reduced the rates of acute rejection, but this has not been followed by a comparable reduction in long-term graft dysfunction rates.