scholarly journals Antibody Conjugates-Recent Advances and Future Innovations

Antibodies ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 2 ◽  
Author(s):  
Donmienne Leung ◽  
Jacqueline M. Wurst ◽  
Tao Liu ◽  
Ruben M. Martinez ◽  
Amita Datta-Mannan ◽  
...  
Keyword(s):  
Drug Targets ◽  
Clinical Success ◽  
Lessons Learned ◽  
Magic Bullet ◽  
Success Rates ◽  
Cell Surface Antigens ◽  
Antibody Conjugates ◽  
Antibody Discovery ◽  
Antibody Conjugation ◽  
Made In

Monoclonal antibodies have evolved from research tools to powerful therapeutics in the past 30 years. Clinical success rates of antibodies have exceeded expectations, resulting in heavy investment in biologics discovery and development in addition to traditional small molecules across the industry. However, protein therapeutics cannot drug targets intracellularly and are limited to soluble and cell-surface antigens. Tremendous strides have been made in antibody discovery, protein engineering, formulation, and delivery devices. These advances continue to push the boundaries of biologics to enable antibody conjugates to take advantage of the target specificity and long half-life from an antibody, while delivering highly potent small molecule drugs. While the “magic bullet” concept produced the first wave of antibody conjugates, these entities were met with limited clinical success. This review summarizes the advances and challenges in the field to date with emphasis on antibody conjugation, linker-payload chemistry, novel payload classes, absorption, distribution, metabolism, and excretion (ADME), and product developability. We discuss lessons learned in the development of oncology antibody conjugates and look towards future innovations enabling other therapeutic indications.

scholarly journals Introduction to Antibody-Drug Conjugates

Antibodies ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 42
Author(s):  
Mark C. Pettinato
Keyword(s):  
The United States ◽  
Resistance Mechanisms ◽  
Lessons Learned ◽  
Antibody Drug Conjugates ◽  
Drug Conjugates ◽  
United States Food ◽  
Antibody Conjugates ◽  
Antibody Discovery ◽  
Drug Antibody Ratio ◽  
Antibody Drug

Antibody-drug conjugates (ADCs) are innovative biopharmaceutical products in which a monoclonal antibody is linked to a small molecule drug with a stable linker. Most of the ADCs developed so far are for treating cancer, but there is enormous potential for using ADCs to treat other diseases. Currently, ten ADCs have been approved by the United States Food and Drug Administration (FDA), and more than 90 ADCs are under worldwide clinical development. Monoclonal antibodies have evolved from research tools to powerful therapeutics in the past 30 years. Tremendous strides have been made in antibody discovery, protein bioengineering, formulation, and delivery devices. This manuscript provides an overview of the biology, chemistry, and biophysical properties of each component of ADC design. This review summarizes the advances and challenges in the field to date, with an emphasis on antibody conjugation, linker-payload chemistry, novel payload classes, drug-antibody ratio (DAR), and product development. The review emphasizes the lessons learned in the development of oncology antibody conjugates and look towards future innovations enabling other therapeutic indications. The review discusses resistance mechanisms to ADCs, and give an opinion on future perspectives.

scholarly journals H3ABioNet genomic medicine and microbiome data portals hackathon proceedings

Database ◽  
2021 ◽  
Vol 2021 ◽  
Author(s):  
Faisal M Fadlelmola ◽  
Kais Ghedira ◽  
Yosr Hamdi ◽  
Mariem Hanachi ◽  
Fouzia Radouani ◽  
...  
Keyword(s):  
Ethnic Groups ◽  
Genomic Medicine ◽  
Lessons Learned ◽  
Team Work ◽  
Significant Progress ◽  
Team Members ◽  
Pan African ◽  
Scientific Expertise ◽  
Microbiome Data ◽  
Made In

Abstract African genomic medicine and microbiome datasets are usually not well characterized in terms of their origin, making it difficult to find and extract data for specific African ethnic groups or even countries. The Pan-African H3Africa Bioinformatics Network (H3ABioNet) recognized the need for developing data portals for African genomic medicine and African microbiomes to address this and ran a hackathon to initiate their development. The two portals were designed and significant progress was made in their development during the hackathon. All the participants worked in a very synergistic and collaborative atmosphere in order to achieve the hackathon's goals. The participants were divided into content and technical teams and worked over a period of 6 days. In response to one of the survey questions of what the participants liked the most during the hackathon, 55% of the hackathon participants highlighted the familial and friendly atmosphere, the team work and the diversity of team members and their expertise. This paper describes the preparations for the portals hackathon and the interaction between the participants and reflects upon the lessons learned about its impact on successfully developing the two data portals as well as building scientific expertise of younger African researchers. Database URL: The code for developing the two portals was made publicly available in GitHub repositories: [https://github.com/codemeleon/Database; https://github.com/codemeleon/AfricanMicrobiomePortal].

scholarly journals Comparison of different techniques for the management of venous steno-occlusive lesions during placement of peripherally inserted central catheter

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Woo Jin Yang ◽  
Danbee Kang ◽  
Ji Hoon Shin ◽  
Eun Ho Jang ◽  
Seung Yeon Noh ◽  
...  
Keyword(s):  
Clinical Success ◽  
Alternative Pathway ◽  
Transluminal Angioplasty ◽  
Second Line ◽  
Peripherally Inserted Central Catheter ◽  
Central Catheter ◽  
Success Rates ◽  
Initial Attempt ◽  
Technical Success Rate ◽  
Occlusive Lesion

AbstractThe purpose of this study is to investigate strategies for peripherally inserted central catheter (PICC) placement in patients with venous steno-occlusive lesion (VSOL). We performed a retrospective cohort study in adults with central or peripheral VSOL who underwent PICC placement procedures from January 2015 to December 2018. Four different strategies [selecting alternative pathway/over the wire (SAP/OTW), percutaneous transluminal angioplasty (PTA), re-puncture in ipsilateral arm (RIA), and catheter placement in the contralateral arm (CICA)] were analyzed and we compared the clinical outcomes by strategy and compared the strategy between central and peripheral VSOLs. During 4 years, 258 PICC procedures performed in patients with VSOLs, 100 PICC were included in the analysis. The overall technical success rate of initial attempt with SAP/OTW was 32.2%. As a second-line technique, PTA was most frequently used in both central (100%) and peripheral (68.2%) VSOL groups. The clinical success rates within 2 months of SAP/OTW, PTA, RIA, CICA were 55.2%, 43.2%, 14.3%, and 33.3%, respectively (P = 0.24). In conclusion, when the SAP/OTW failed, the PTA can be preferred as a second-line technique for both central and peripheral VSOLs. When guidewire passage fails, the operator could adopt the RIA or CICA technique as an alternative method.

scholarly journals Surgical outcome of percutaneous transhepatic gallbladder drainage in acute cholecystitis: Ten years’ experience at a tertiary care centre

2021 ◽  
Author(s):  
Szabolcs Ábrahám ◽  
Illés Tóth ◽  
Ria Benkő ◽  
Mária Matuz ◽  
Gabriella Kovács ◽  
...  
Keyword(s):  
Hospital Mortality ◽  
Acute Cholecystitis ◽  
Conversion Rate ◽  
Clinical Success ◽  
Definitive Treatment ◽  
Success Rates ◽  
Female Ratio ◽  
Gallbladder Drainage ◽  
Percutaneous Transhepatic Gallbladder Drainage ◽  
Grade Iii

Abstract Background Percutaneous transhepatic gallbladder drainage (PTGBD) plays an important role in the treatment of elderly patients and/or patients in poor health with acute cholecystitis (AC). The primary aim of this study is to determine how these factors influence the clinical outcome of PTGBD. Moreover, we assessed the timing and results of subsequent cholecystectomies. Patients and Methods We retrospectively examined the results of 162 patients undergoing PTGBD between 2010 and 2020 (male–female ratio: 51.23% vs. 48.77%; mean age: 71.43 ± 13.22 years). Patient’s performance status and intervention outcomes were assessed with clinical success rates (CSR) and in-hospital mortality. The conversion rate (CR) of possible urgent or delayed, elective laparoscopic cholecystectomies (LC) after PTGBD were analysed. Results PTGBD was the definitive treatment in 42.18% of patients, while it was a bridging therapy prior to cholecystectomy (CCY) for the other patients. CSR was 87.97%, it was only 64.29% in grade III AC. In 9.87% of the cases, urgent LC was necessary after PTGBD, and its conversion rate was approximately equal to that of elective LC (18.18 vs. 17.46%, respectively, p = 0.2217). Overall, the post-PTGBD in-hospital mortality was 11.72%, while the same figure was 0% for grade I AC, 7.41% for grade II and 40.91% for grade III. Based on logistic regression analyses, in-hospital mortality (OR 6.07; CI 1.79–20.56), clinical progression (OR 7.62; CI 2.64–22.05) and the need for emergency CCY (OR 14.75; CI 3.07–70.81) were mostly determined by AC severity grade. Conclusion PTGBD is an easy-to-perform intervention with promising clinical success rates in the treatment of acute cholecystitis. After PTGBD, the level of gallbladder inflammation played a decisive role in the course of AC. In a severe, grade III inflammation, we have to consider low CSR and high mortality.

scholarly journals Whither Magnetic Hyperthermia? A Tentative Roadmap

Materials ◽  
2021 ◽  
Vol 14 (4) ◽  
pp. 706
Author(s):  
Irene Rubia-Rodríguez ◽  
Antonio Santana-Otero ◽  
Simo Spassov ◽  
Etelka Tombácz ◽  
Christer Johansson ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Nanoparticle Synthesis ◽  
Careful Analysis ◽  
Magnetic Hyperthermia ◽  
Lessons Learned ◽  
In Vivo Testing ◽  
Evolution Of Science ◽  
Made In ◽  
Critical Aspects

The scientific community has made great efforts in advancing magnetic hyperthermia for the last two decades after going through a sizeable research lapse from its establishment. All the progress made in various topics ranging from nanoparticle synthesis to biocompatibilization and in vivo testing have been seeking to push the forefront towards some new clinical trials. As many, they did not go at the expected pace. Today, fruitful international cooperation and the wisdom gain after a careful analysis of the lessons learned from seminal clinical trials allow us to have a future with better guarantees for a more definitive takeoff of this genuine nanotherapy against cancer. Deliberately giving prominence to a number of critical aspects, this opinion review offers a blend of state-of-the-art hints and glimpses into the future of the therapy, considering the expected evolution of science and technology behind magnetic hyperthermia.

scholarly journals Novel therapeutic interventions towards improved management of septic arthritis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jian Wang ◽  
Liucai Wang
Keyword(s):  
Antibiotic Therapy ◽  
Septic Arthritis ◽  
Clinical Success ◽  
Treatment Protocol ◽  
Current Treatment ◽  
Therapeutic Interventions ◽  
Medical Emergency ◽  
Success Rates ◽  
Joint Infections ◽  
Novel Therapeutic

AbstractSeptic arthritis (SA) represents a medical emergency that needs immediate diagnosis and urgent treatment. Despite aggressive treatment and rapid diagnosis of the causative agent, the mortality and lifelong disability, associated with septic arthritis remain high as close to 11%. Moreover, with the rise in drug resistance, the rates of failure of conventional antibiotic therapy have also increased. Among the etiological agents frequently isolated from cases of septic arthritis, Staphylococcus aureus emerges as a dominating pathogen, and to worsen, the rise in methicillin-resistant S. aureus (MRSA) isolates in bone and joint infections is worrisome. MRSA associated cases of septic arthritis exhibit higher mortality, longer hospital stay, and higher treatment failure with poorer clinical outcomes as compared to cases caused by the sensitive strain i.e methicillin-sensitive S. aureus (MSSA).In addition to this, equal or even greater damage is imposed by the exacerbated immune response mounted by the patient’s body in a futile attempt to eradicate the bacteria. The antibiotic therapy may not be sufficient enough to control the progression of damage to the joint involved thus, adding to higher mortality and disability rates despite the prompt and timely start of treatment. This situation implies that efforts and focus towards studying/understanding new strategies for improved management of sepsis arthritis is prudent and worth exploring.The review article aims to give a complete insight into the new therapeutic approaches studied by workers lately in this field. To the best of our knowledge studies highlighting the novel therapeutic strategies against septic arthritis are limited in the literature, although articles on pathogenic mechanism and choice of antibiotics for therapy, current treatment algorithms followed have been discussed by workers in the past. The present study presents and discusses the new alternative approaches, their mechanism of action, proof of concept, and work done so far towards their clinical success. This will surely help to enlighten the researchers with comprehensive knowledge of the new interventions that can be used as an adjunct therapy along with conventional treatment protocol for improved success rates.

Factors Influencing Clinical Success Following Endovascular Treatment of Type II Endoleaks

2020 ◽  
pp. 084653712098110
Author(s):  
Ramin Hamidizadeh ◽  
Emeka Nzekwu ◽  
Oliver Halliwell
Keyword(s):  
Clinical Success ◽  
Strong Predictor ◽  
Graft Infection ◽  
Mortality Data ◽  
Complication Rates ◽  
Type Ii ◽  
Success Rates ◽  
Cyanoacrylate Glue ◽  
Embolic Agents ◽  
Predictor Of Success

Purpose: To compare long-term outcomes of transarterial (TA) and translumbar (TL) embolization of type II endoleaks (T2E) following EVAR, as well as factors that predict clinical success. Methods: 129 (mean age, 71.4y; range, 53-95) with T2E referred for embolization from August-2003 to December-2017 were retrospectively reviewed. One-hundred-eighty procedures were performed via TA (n = 139) and TL (n = 41) approaches, with 37 patients undergoing 51 reinterventions. Clinical success was defined as absence of endoleak and/or absence of aneurysm sac enlargement on follow-up imaging. Medical comorbidities, procedural data, embolic agents used, presence of successful sac embolization, and 30-day morbidity and mortality data were collected. Results: TL approaches had higher technical success (41/41 vs.122/139, p = .014). Clinical success rates were 52% (N = 58/111) and 62% (N = 23/37) for TA and TL procedures respectively ( p = .34). Looking at all procedures, sac embolization using n-butyl cyanoacrylate glue had higher clinical success compared to other embolic agents ( p = .017-.037). Successful sac access was a strong predictor of success for TA procedures (46/78 vs.12/33, p = .0379). 30-day complication rates were similar between TA (5.8%) and TL (4.9%) approaches. There was 1 death secondary to graft infection following TA embolization. Conclusions: Overall clinical success of TA and TL embolization when considering re-interventions is high. n-butyl cyanoacrylate glue had significantly higher success than other embolic agents ( p = .017-.037). Successful sac access was associated with success for TA procedures.

scholarly journals One-year outcomes of microhook trabeculotomy versus suture trabeculotomy ab interno

2021 ◽  
Author(s):  
Hiroshi Yokoyama ◽  
Masashi Takata ◽  
Fumi Gomi
Keyword(s):  
Survival Analysis ◽  
Clinical Success ◽  
Treatment Success ◽  
Medication Use ◽  
Glaucoma Surgery ◽  
Success Rates ◽  
Kaplan Meier ◽  
One Year ◽  
Ab Interno

Abstract Purpose To compare clinical success rates and reductions in intraocular pressure (IOP) and IOP-lowering medication use following suture trabeculotomy ab interno (S group) or microhook trabeculotomy (μ group). Methods This retrospective review collected data from S (n = 104, 122 eyes) and μ (n = 42, 47 eyes) groups who underwent treatment between June 1, 2016, and October 31, 2019, and had 12-month follow-up data including IOP, glaucoma medications, complications, and additional IOP-lowering procedures. The Kaplan–Meier survival analysis was used to evaluate treatment success rates defined as normal IOP (> 5 to ≤ 18 mm Hg), ≥ 20% reduction of IOP from baseline at two consecutive visits, and no further glaucoma surgery. Results Schlemm’s canal opening was longer in the S group than in the μ group (P < 0.0001). The Kaplan–Meier survival analysis of all eyes showed cumulative clinical success rates in S and µ groups were 71.1% and 61.7% (P = 0.230). The Kaplan–Meier survival analysis of eyes with preoperative IOP ≥ 21 mmHg showed cumulative clinical success rates in S and μ groups were 80.4% and 60.0% (P = 0.0192). There were no significant differences in postoperative IOP at 1, 3, and 6 months (S group, 14.9 ± 5.6, 14.6 ± 4.5, 14.6 ± 3.9 mmHg; μ group, 15.8 ± 5.9, 15.2 ± 4.4, 14.7 ± 3.7 mmHg; P = 0.364, 0.443, 0.823), but postoperative IOP was significantly lower in the S group at 12 months (S group, 14.1 ± 3.1 mmHg; μ group, 15.6 ± 4.1 mmHg; P = 0.0361). There were no significant differences in postoperative numbers of glaucoma medications at 1, 3, 6, and 12 months (S group, 1.8 ± 1.6, 1.8 ± 1.5, 2.0 ± 1.6, 1.8 ± 1.5; μ group, 2.0 ± 1.6, 2.0 ± 1.6, 2.1 ± 1.6, 2.2 ± 1.7; P = 0.699, 0.420, 0.737, 0.198). Conclusion S and µ group eyes achieved IOP reduction, but μ group eyes had lower clinical success rates among patients with high preoperative IOP at 12 months.

scholarly journals Deploying triple artemisinin-based combination therapy (TACT) for malaria treatment in Africa: ethical and practical considerations

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Paulina Tindana ◽  
Freek de Haan ◽  
Chanaki Amaratunga ◽  
Mehul Dhorda ◽  
Rob W. van der Pluijm ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Combination Therapy ◽  
Southeast Asia ◽  
Malaria Control ◽  
Lessons Learned ◽  
Line Treatment ◽  
African Continent ◽  
First Line ◽  
First Line Treatment ◽  
Made In

AbstractMalaria remains a major cause of morbidity and mortality in Africa, particularly in children under five years of age. Availability of effective anti-malarial drug treatment is a cornerstone for malaria control and eventual malaria elimination. Artemisinin-based combination therapy (ACT) is worldwide the first-line treatment for uncomplicated falciparum malaria, but the ACT drugs are starting to fail in Southeast Asia because of drug resistance. Resistance to artemisinins and their partner drugs could spread from Southeast Asia to Africa or emerge locally, jeopardizing the progress made in malaria control with the increasing deployment of ACT in Africa. The development of triple artemisinin-based combination therapy (TACT) could contribute to mitigating the risks of artemisinin and partner drug resistance on the African continent. However, there are pertinent ethical and practical issues that ought to be taken into consideration. In this paper, the most important ethical tensions, some implementation practicalities and preliminary thoughts on addressing them are discussed. The discussion draws upon data from randomized clinical studies using TACT combined with ethical principles, published literature and lessons learned from the introduction of artemisinin-based combinations in African markets.

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