{"title":"Why and How Should Ethiopia Establish a Stem Cell Transplant Service? A Review Article.","authors":"Sintayehu Mekonnen, Hawi Farris","doi":"10.2147/BTT.S401289","DOIUrl":"https://doi.org/10.2147/BTT.S401289","url":null,"abstract":"<p><p>Ethiopia is attempting to reduce cancer-related morbidity and mortality through a strategic national cancer control plan but according to Globocan 2020, hematologic malignancies particularly leukemia and non-Hodgkin's lymphoma rank among the top five leading causes of new cancer incidence and cause of death among all age groups in both sexes. Hematopoietic stem-cell transplantation (HSCT) is an advanced treatment modality that makes the only effective treatment for cancer and non-cancer-related hematologic diseases unresponsive to conventional therapy. Patients who need stem cell transplants must travel to abroad countries to get the treatment. Meanwhile, the Ethiopian National Specialty and Subspecialty Roadmap sets the goal of establishing HSCT centers in 2020-2029 GC, yet leaders and planners must start taking steps to put the setup in place. Setting up an HSCT facility is challenging for developing countries due to the high costs, limited infrastructure, and need for intensive medical staff training; however, several nations have been able to start successful stem cell transplant programs. This review summarizes the basic steps and requirements of the program in light of guidelines recommendations and lessons learned from other developing countries. It also highlights possible cost-effective opportunities, bottlenecks, and areas that will require work and investment to make the objective reality in Ethiopia. Provides key information to assist administrators and policymakers to set priorities in planning and making informed decisions to establish and maintain the service.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"17 ","pages":"33-40"},"PeriodicalIF":4.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ca/8c/btt-17-33.PMC10038007.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9545572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. Mykoniatis, Stavros Tsiakaras, M. Samarinas, A. Anastasiadis, E. N. Symeonidis, P. Sountoulides
{"title":"Monoclonal Antibody Therapy for the Treatment of Interstitial Cystitis","authors":"I. Mykoniatis, Stavros Tsiakaras, M. Samarinas, A. Anastasiadis, E. N. Symeonidis, P. Sountoulides","doi":"10.2147/BTT.S290286","DOIUrl":"https://doi.org/10.2147/BTT.S290286","url":null,"abstract":"Abstract An emerging theory regarding the potentially autoimmune nature of painful bladder syndrome/interstitial cystitis (PBS/IC) had led to several studies being conducted to assess the possible therapeutic effect of immunotherapeutic options for PBS/IC. This review presents the available evidence regarding the potential autoimmunity-based pathogenesis of PBS/IC and focuses on a main representative of the immunotherapeutic modalities for PBS/IC, aiming to summarize, evaluate, and present available data regarding the potential therapeutic role of monoclonal antibodies for PBS/IC patients. A non-systematic narrative and interpretative literature review was performed. The monoclonal antibodies included in the review were the anti-tumor necrosis factor-α (anti-TNF-α) agents adalimumab, which showed no difference compared to placebo, and certolizumab pegol, which showed statistically important differences in all outcome measures compared to placebo at the 18-week follow-up visit. Anti-nerve growth factor (anti-NGF) agents were also reviewed, including tanezumab, which showed both positive and negative efficacy results compared to placebo, and fulranumab, the study of which was discontinued owing to adverse events. In summary, monoclonal antibody therapy remains to be further researched in order for it to be proposed as a promising future treatment option for PBS/IC.","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"16 1","pages":"47 - 55"},"PeriodicalIF":4.0,"publicationDate":"2022-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47970705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y. T. Dabi, H. Andualem, S. T. Degechisa, S. T. Gizaw
{"title":"Targeting Metabolic Reprogramming of T-Cells for Enhanced Anti-Tumor Response","authors":"Y. T. Dabi, H. Andualem, S. T. Degechisa, S. T. Gizaw","doi":"10.2147/BTT.S365490","DOIUrl":"https://doi.org/10.2147/BTT.S365490","url":null,"abstract":"Abstract Cancer immunotherapy is an effective treatment option against cancer. One of the approaches of cancer immunotherapy is the modification of T cell-based anti-tumor immune responses. T-cells, a type of adaptive immune response cells responsible for cell-mediated immunity, have long been recognized as key regulators of immune-mediated anti-tumor immunity. T-cell activities have been reported to be suppressed or enhanced by changes in cell metabolism. Moreover, metabolic reprogramming during activation of T cells is required for the development of distinct differentiation profiles of these cells, which may allow the development of long-term cell-mediated anti-tumor immunity. However, T cells have been shown to undergo metabolic exhaustion in tumor microenvironment (TME) as it poses several obstacles to their function. Applications of several mechanistic solutions to improve the efficacy of T cell-based therapies including chimeric antigen receptor (CAR) T cell therapy are yet to be determined. Modifying the metabolic properties of these cells and employing them in cancer immunotherapy is a potential strategy for improving their anti-tumor activity and therapeutic efficacy. To give an insight, in this review paper, we endeavoured to cover metabolic reprogramming in cancer and T cells, signalling mechanisms involved in immuno-metabolic regulation, the effects of the TME on T cell metabolic fitness, and targeting metabolic reprogramming of T cells for an enhanced anti-tumor response.","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"16 1","pages":"35 - 45"},"PeriodicalIF":4.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42016582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Progress in Biological Therapies for Adult-Onset Still’s Disease","authors":"P. Galozzi, S. Bindoli, A. Doria, P. Sfriso","doi":"10.2147/BTT.S290329","DOIUrl":"https://doi.org/10.2147/BTT.S290329","url":null,"abstract":"Abstract Adult-onset Still’s disease (AOSD) is a rare multifactorial autoinflammatory disorder of unknown etiology, characterized by an excessive release of cytokines triggered by dysregulated inflammation and articular and systemic manifestations. The clinical spectrum of AOSD ranges from self-limiting forms with mild symptoms to life-threatening cases and presents clinical and biological similarities with the juvenile form (sJIA). Nowadays, the advances in biologic agents no longer limit the treatment to NSAIDs, glucocorticoids, or conventional synthetic DMARDs. The blockade of IL-1 and IL-6 is effective in the treatment of systemic and articular inflammation of AOSD patients; however, novel compounds with different properties and targets are now available and others are being studied. In this review, starting from the pathogenesis of AOSD, we summarized the current and emerging biological therapies, possible effective agents for achieving AOSD control and remission.","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"16 1","pages":"21 - 34"},"PeriodicalIF":4.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47547261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Continuous Use of Etanercept During Pregnancy Does Not Affect TNF-Alpha Levels in Umbilical Cord Blood","authors":"Masayuki Nishide, Mayu Yagita, A. Kumanogoh","doi":"10.2147/BTT.S358449","DOIUrl":"https://doi.org/10.2147/BTT.S358449","url":null,"abstract":"Abstract TNF-alpha-targeted therapies during pregnancy is a topic of interest in rheumatology. Etanercept (ETN) is expected to have lower transplacental transfer, however, clinical evidence is lacking on the usefulness and safeness of continuing etanercept throughout pregnancy. We here described the first reported case of relapsing polychondritis where continuous use of ETN throughout pregnancy was required. The patient was a pregnant Japanese woman who presented with bilateral ear cartilage redness, swelling, saddle nose and severe subglottic oedema. Due to severe systemic and life-threatened disease, we decided to continue using ETN throughout pregnancy and resulted in successful vaginal delivery. The treatment with ETN was successful and TNF-alpha levels in umbilical cord blood were not affected. The infant did not have any signs of chondritis although levels of anti-type 2 collagen antibodies in maternal and umbilical cord blood were similar, suggesting that anti-type 2 collagen antibodies crossed the placenta. This case is an important clinical experience that strengthens the safety to continue ETN during the entire pregnancy if necessary.","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"16 1","pages":"17 - 19"},"PeriodicalIF":4.0,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46134943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Temraz, F. Nasr, J. Kattan, D. Abigerges, W. Moukadem, F. Farhat, L. Maatouk, G. Chahine, A. Shamseddine
{"title":"A Non-Interventional Multicenter Study of First-Line Bevacizumab in Combination with Chemotherapy in Patients with Metastatic Colorectal Cancer in Lebanon","authors":"S. Temraz, F. Nasr, J. Kattan, D. Abigerges, W. Moukadem, F. Farhat, L. Maatouk, G. Chahine, A. Shamseddine","doi":"10.2147/BTT.S340525","DOIUrl":"https://doi.org/10.2147/BTT.S340525","url":null,"abstract":"Purpose When combined with chemotherapy, bevacizumab improves progression-free survival (PFS) in metastatic colorectal cancer (mCRC). This observational trial was designed to assess the safety and efficacy of bevacizumab plus first-line chemotherapy in a real-world setting in Lebanon. Patients and Methods A non-interventionaL multicenter study of first-LIne AVastin® (bevacizumab) in combination with chEmotherapy in patients with metastatic colorectal cancer (LLIVE) is a multicenter, prospective, Lebanon-based, observational study that enrolled mCRC patients who received first-line bevacizumab plus chemotherapy combination. The primary end point of the study was PFS. Secondary endpoints comprised the overall response rate (ORR) and the safety and tolerability of bevacizumab. Results A total of 196 patients were enrolled between July 2010 and August 2013. The median duration of follow-up was 11 months. Median duration of bevacizumab treatment was 4 months with FOLFOX being the chiefly chemotherapy regimen used in the first-line setting (26%). Median PFS was 8.22 months (95% confidence interval (CI): 7.005–9.443). The ORR was 50.3% (complete response 7.5%, partial response 42.8%). The most common adverse event encountered was hypertension (28%) followed by epistaxis (4.8%), diarrhea (4%), anemia (4%) and headache (4%). Grade 3/4 adverse events occurred in 15.2% of patients. Conclusion The trial further substantiated the efficacy and safety of bevacizumab and chemotherapy in the first-line treatment of mCRC patients in Lebanon.","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"16 1","pages":"7 - 15"},"PeriodicalIF":4.0,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48063634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A Review on Inflammatory Bowel Diseases: Recent Molecular Pathophysiology Advances.","authors":"Maheeba Abdulla, Nafeesa Mohammed","doi":"10.2147/BTT.S380027","DOIUrl":"https://doi.org/10.2147/BTT.S380027","url":null,"abstract":"<p><p>Inflammatory bowel diseases are considered immune disorders with a complex genetic architecture involving constantly changing endogenous and exogenous factors. The rapid evolution of genomic technologies and the emergence of newly discovered molecular actors are compelling the research community to reevaluate the knowledge and molecular processes. The human intestinal tract contains intestinal human microbiota consisting of commensal, pathogenic, and symbiotic strains leading to immune responses that can contribute and lead to both systemic and intestinal disorders including IBD. In this review, we attempted to highlight some updates of the new IBD features related to genomics, microbiota, new emerging therapies and some major established IBD risk factors.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"16 ","pages":"129-140"},"PeriodicalIF":4.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b8/ae/btt-16-129.PMC9481278.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9925276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Timothy Fitzgerald, Richard Melsheimer, Marie-Hélène Lafeuille, Patrick Lefebvre, Laura Morrison, Kimberly Woodruff, Iris Lin, Bruno Emond
{"title":"Switching and Discontinuation Patterns Among Patients Stable on Originator Infliximab Who Switched to an Infliximab Biosimilar or Remained on Originator Infliximab.","authors":"Timothy Fitzgerald, Richard Melsheimer, Marie-Hélène Lafeuille, Patrick Lefebvre, Laura Morrison, Kimberly Woodruff, Iris Lin, Bruno Emond","doi":"10.2147/BTT.S285610","DOIUrl":"10.2147/BTT.S285610","url":null,"abstract":"<p><strong>Objective: </strong>To compare switching and discontinuation patterns of patients stable on originator infliximab (IFX) who switched to an IFX biosimilar (switchers) or remained on originator IFX (continuers) in the United States.</p><p><strong>Methods: </strong>Symphony Health Solutions' Patient Transactional Datasets (10/2012-03/2019) were used to identify adults with ≥2 claims for either rheumatoid arthritis (RA), psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, or inflammatory bowel disease (IBD); and ≥1 claim for originator or biosimilar IFX. The index date was the first IFX biosimilar claim for switchers or a random originator IFX claim for continuers. All patients were required to have ≥5 originator IFX claims during the 12 months pre-index (prevalent population). The subset of patients with ≥12 months of observation prior to the first originator IFX claim was also analyzed (incident population). Switchers were matched 1:3 to continuers. Discontinuation was defined as having ≥120 days between 2 consecutive index treatment claims.</p><p><strong>Results: </strong>Prevalent switchers (N=1109) were 3.57-times more likely than continuers (N=3327) to switch to another originator biologic (hazard ratio [HR]=3.57, p<0.001). Of 249 prevalent switchers who switched to another originator biologic, 200 (80.3%) switched back to originator IFX. Incident switchers (N=571) were 2.55-times more likely than continuers (N=1713) to switch to another originator biologic (HR=2.55, p<0.001). Of 118 incident switchers who switched to another originator biologic, 90 (76.3%) switched back to originator IFX. Prevalent switchers were 1.25-times more likely than continuers to discontinue index therapy (HR=1.25, p<0.001). Similar results were observed in RA (prevalent population; switching: HR=3.49, p<0.001; discontinuation: HR=1.23, p=0.009) and IBD (prevalent population; switching: HR=3.82, p<0.001; discontinuation: HR=1.29, p=0.003) subgroups.</p><p><strong>Conclusion: </strong>Patients switching from originator to biosimilar IFX were more likely to switch to another originator biologic (notably back to originator IFX) and discontinue index treatment than those remaining on originator IFX; however, reasons for switching are unknown.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"15 ","pages":"1-15"},"PeriodicalIF":5.3,"publicationDate":"2021-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/47/f3/btt-15-1.PMC7797299.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10343101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"How Can We Engineer CAR T Cells to Overcome Resistance?","authors":"Maya Glover, Stephanie Avraamides, John Maher","doi":"10.2147/BTT.S252568","DOIUrl":"https://doi.org/10.2147/BTT.S252568","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T cell therapy has achieved unrivalled success in the treatment of B cell and plasma cell malignancies, with five CAR T cell products now approved by the US Food and Drug Administration (FDA). However, CAR T cell therapies for solid tumours have not been nearly as successful, owing to several additional challenges. Here, we discuss mechanisms of tumour resistance in CAR T cell therapy and the emerging strategies that are under development to engineer CAR T cells to overcome resistance.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"15 ","pages":"175-198"},"PeriodicalIF":4.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/52/56/btt-15-175.PMC8141613.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9578933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Glycopeptides as Potential Interventions for COVID-19.","authors":"Desalegn Getnet Demsie, Abadi Kahsu Gebre, Ebrahim M Yimer, Niguse Meles Alema, Ephrem Mebrahtu Araya, Abere Tilahun Bantie, Mengesha Dessie Allene, Hagazi Gebremedhin, Adane Yehualaw, Chernet Tafere, Haileslassie Tesfay Tadese, Bekalu Amare, Etsay Weldekidan, Desye Gebrie","doi":"10.2147/BTT.S262705","DOIUrl":"https://doi.org/10.2147/BTT.S262705","url":null,"abstract":"<p><p>Coronavirus disease 2019 (COVID-19), an infectious disease that primarily attacks the human pulmonary system, is caused by a viral strain called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The outbreak emerged from Wuhan, China, and later spread throughout the world. Until the first week of May 2020, over 3.7 million cases had been reported worldwide and more than 258,000 had died due to the disease. So far, off label use of various drugs has been tried in many clinical settings, however, at present, there is no vaccine or antiviral treatment for human and animal coronaviruses. Therefore, repurposing of the available drugs may be promising to control emerging infections of SARS-COV2; however, new interventions are likely to require months to years to develop. Glycopeptides, which are active against gram-positive bacteria, have demonstrated significant activity against viral infections including SARS-COV and MERS-COV and have a high resemblance of sequence homology with SARS-COV2. Recent in vitro studies have also shown promising activities of aglycon derivative of glycopeptides and teicoplanin against SARS-COV2. Hydrophobic aglycon derivatives and teicoplanin, with minimal toxicity to human cell lines, inhibit entry and replication of SARS-COV2. These drugs block proteolysis of polyprotein a/b with replicase and transcription domains. Teicoplanin use was associated with complete viral clearance in a cohort of patients with severe COVID-19 symptoms. This review attempts to describe the activity, elucidate the possible mechanisms and potential clinical applications of existing glycopeptides against corona viruses, specifically SARS-COV2.</p>","PeriodicalId":9025,"journal":{"name":"Biologics : Targets & Therapy","volume":"14 ","pages":"107-114"},"PeriodicalIF":4.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/BTT.S262705","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10849878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}