The Experts below are selected from a list of 84 Experts worldwide ranked by ideXlab platform
Janice M Reichert - One of the best experts on this subject based on the ideXlab platform.
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Development trends for human monoclonal antibody therapeutics
Nature Reviews Drug Discovery, 2010Co-Authors: Aaron L. Nelson, Eugen Dhimolea, Janice M ReichertAbstract:Fully human monoclonal antibodies (mAbs), which have the potential to be less immunogenic than earlier humanized and chimeric mAbs, are the most rapidly growing class of mAbs in clinical development. Here, Reichert and colleagues highlight trends in the development of human mAbs, seven of which have so far gained regulatory approval. Fully human monoclonal antibodies (mAbs) are a promising and rapidly growing category of targeted therapeutic agents. The first such agents were developed during the 1980s, but none achieved clinical or commercial success. Advances in technology to generate the molecules for study — in particular, transgenic mice and yeast or phage display — renewed interest in the development of human mAbs during the 1990s. In 2002, adalimumab became the first human mAb to be approved by the US Food and Drug Administration (FDA). Since then, an additional six human mAbs have received FDA approval: panitumumab, golimumab, canakinumab, ustekinumab, ofatumumab and denosumab. In addition, 3 candidates (Raxibacumab, belimumab and ipilimumab) are currently under review by the FDA, 7 are in Phase III studies and 81 are in either Phase I or II studies. Here, we analyse data on 147 human mAbs that have entered clinical study to highlight trends in their development and approval, which may help inform future studies of this class of therapeutic agents.
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Development trends for human monoclonal antibody therapeutics
Nature Reviews Drug Discovery, 2010Co-Authors: Aaron L. Nelson, Eugen Dhimolea, Janice M ReichertAbstract:Fully human monoclonal antibodies (mAbs) are a promising and rapidly growing category of targeted therapeutic agents. The first such agents were developed during the 1980s, but none achieved clinical or commercial success. Advances in technology to generate the molecules for study - in particular, transgenic mice and yeast or phage display - renewed interest in the development of human mAbs during the 1990s. In 2002, adalimumab became the first human mAb to be approved by the US Food and Drug Administration (FDA). Since then, an additional six human mAbs have received FDA approval: panitumumab, golimumab, canakinumab, ustekinumab, ofatumumab and denosumab. In addition, 3 candidates (Raxibacumab, belimumab and ipilimumab) are currently under review by the FDA, 7 are in Phase III studies and 81 are in either Phase I or II studies. Here, we analyse data on 147 human mAbs that have entered clinical study to highlight trends in their development and approval, which may help inform future studies of this class of therapeutic agents.
Thi-sau Migone - One of the best experts on this subject based on the ideXlab platform.
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added benefit of Raxibacumab to antibiotic treatment of inhalational anthrax
Antimicrobial Agents and Chemotherapy, 2015Co-Authors: Thi-sau Migone, John Zhong, Al Corey, Sally D Bolmer, Daphne Vasconcelos, Matthew Buccellato, Gabriel T MeisterAbstract:Although antibiotics treat bacteremia in inhalational anthrax, pathogenesis is mainly driven by bacterial exotoxins. Raxibacumab, an IgG1 monoclonal antibody, binds the protective antigen (PA) of Bacillus anthracis, thus blocking toxin effects and leading to improved survival in the rabbit and monkey models of inhalational anthrax. To assess Raxibacumab's added benefit over levofloxacin (LVX) alone, rabbits surviving to 84 h after a challenge with 200 times the median (50%) lethal dose of B. anthracis spores were randomized to receive 3 daily intragastric LVX doses of 50 mg/kg of body weight, with the first LVX dose administered just prior to administration of a single intravenous dose of placebo or 40 mg/kg Raxibacumab. The percentages of animals alive at 28 days following the last LVX dose were compared between the 2 treatment groups using a two-sided likelihood-ratio chi-square test. The 82% survival rate for the LVX-Raxibacumab combination was higher than the 65% survival rate for LVX alone (P = 0.0874). There were nearly 2-fold fewer deaths for the combination (7 deaths; n = 39) than for LVX alone (13 deaths; n = 37), and the survival time was prolonged for the combination (P = 0.1016). Toxin-neutralizing-activity titers were similar for both treatment groups, suggesting that survivors in both groups were able to mount a toxin-neutralizing immune response. Microscopic findings considered consistent with anthrax were present in animals that died or became moribund on study in both treatment groups, and there were no anthrax-related findings in animals that survived. Overall, Raxibacumab provided a meaningful benefit over antibiotic alone when administered late in the disease course.
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bacillus anthracis protective antigen kinetics in inhalation spore challenged untreated or levofloxacin Raxibacumab treated new zealand white rabbits
Toxins, 2013Co-Authors: A Corey, Thi-sau Migone, Sally D Bolmer, Michele Fiscella, Christopher W Ward, Cecil Chen, Gabriel MeisterAbstract:Inhaled Bacillus anthracis spores germinate and the subsequent vegetative growth results in bacteremia and toxin production. Anthrax toxin is tripartite: the lethal factor and edema factor are enzymatic moieties, while the protective antigen (PA) binds to cell receptors and the enzymatic moieties. Antibiotics can control B. anthracis bacteremia, whereas Raxibacumab binds PA and blocks lethal toxin effects. This study assessed plasma PA kinetics in rabbits following an inhaled B. anthracis spore challenge. Additionally, at 84 h post-challenge, 42% of challenged rabbits that had survived were treated with either levofloxacin/placebo or levofloxacin/Raxibacumab. The profiles were modeled using a modified Gompertz/second exponential growth phase model in untreated rabbits, with added monoexponential PA elimination in treated rabbits. Shorter survival times were related to a higher plateau and a faster increase in PA levels. PA elimination half-lives were 10 and 19 h for the levofloxacin/placebo and levofloxacin/Raxibacumab groups, respectively, with the difference attributable to persistent circulating PA-Raxibacumab complex. PA kinetics were similar between untreated and treated rabbits, with one exception: treated rabbits had a plateau phase nearly twice as long as that for untreated rabbits. Treated rabbits that succumbed to disease had higher plateau PA levels and shorter plateau duration than surviving treated rabbits.
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Protective Antigen Antibody Augments Hemodynamic Support in Anthrax Lethal Toxin Shock in Canines
The Journal of Infectious Diseases, 2012Co-Authors: Amisha V Barochia, Thi-sau Migone, G. Mani Subramanian, Yan Li, Steven B Solomon, Sally D Bolmer, Peter Q EichackerAbstract:Mortality in patients with shock during the 2001 US anthrax outbreak was high [1, 2]. Although the mechanisms and optimal management of this shock remain unclear, the risk of anthrax persists, as demonstrated by recent cases among injection drug abusers in Europe [3, 4]. Seventeen of 52 patients from this outbreak died, many with progressive shock despite standard intensive care unit (ICU) support. Anthrax bacilli produce 2 toxins: lethal toxin (LT) and edema toxin (ET) [5, 6]. Each is composed of a toxic moiety (lethal factor [LF] or edema factor [EF], respectively) and protective antigen (PA), a component necessary for LF or EF uptake by host cells. LF is a zinc endopeptidase that cleaves mitogen-activated protein kinase kinases (MAPKK), whereas EF is a calmodulin-dependent adenyl cyclase. Of the two, LT is the more lethal and thought to play a central role in the pathogenesis of anthrax shock [7–20]. Despite the contribution of LT-induced shock to the pathogenesis of anthrax, its treatment has received little study. Conventional therapy for septic shock (which would include hemodynamic support with fluid and vasopressor administration titrated to physiologic endpoints like mean arterial pressure) has not been investigated in models of anthrax. In rats, fixed (nontitrated) doses of either normal saline or norepinephrine (NE) administered as 24-hour infusions were beneficial against lipopolysaccharide (LPS) or Escherichia coli challenge, but not LT challenge [20, 21]. Notably, however, inability to titrate these therapies in the LT-challenged rodent model may have produced adverse effects that limited benefit. Besides hemodynamic support, toxin inhibition has also been proposed for the treatment of life-threatening anthrax infection. Both polyclonal (Anthrax Immune Globulin Intravenous [AIGIV], Cangene Corp, Winnipeg, Canada) and monoclonal (Raxibacumab; Human Genome Sciences, Rockville, MD) antibody preparations, directed in part or solely against PA, have been added to the US Strategic National Stockpile. However, whether such preparations have additive benefit when combined with conventionally titrated hemodynamic support is not clear [21–27]. Defining the effects of titrated hemodynamic support, alone or together with protective antigen–directed monoclonal antibody (PA-mAb), for LT-associated shock is important. We previously developed a sedated, instrumented, and mechanically ventilated canine model in which LT, infused over 24 hours to simulate toxin release during infection, produced progressive hypotension and organ dysfunction [16]. We employed this model to investigate the effects of titrated hemodynamic support and PA-directed monoclonal antibody (Raxibacumab) alone or together, for LT-induced shock. Although hemodynamic support was available (if indicated) from the start of toxin infusion, PA-mAb was administered either early at the initiation of toxin (0 hours), or later at 9 or 12 hours to investigate the effect of delayed treatment as might occur clinically.
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Raxibacumab for the treatment of inhalational anthrax
The New England Journal of Medicine, 2009Co-Authors: Thi-sau Migone, John Zhong, Al Corey, Matt Devalaraja, Larry Lo, Janelle Zimmerman, Stephen Ullrich, Mani G Subramanian, Letha Healey, Andrew ChenAbstract:Background Inhalational anthrax caused by Bacillus anthracis is associated with high mortality primarily due to toxin-mediated injury. Raxibacumab is a human IgG1λ monoclonal antibody directed against protective antigen, a component of the anthrax toxin. Methods We evaluated the efficacy of Raxibacumab as a prophylactic agent and after disease onset in a total of four randomized, placebo-controlled studies conducted in rabbits and monkeys. Animals were exposed to an aerosolized target exposure of B. anthracis spores that was approximately 100 times (in the prophylactic studies) and 200 times (in the therapeutic-intervention studies) the median lethal dose. In the therapeutic-intervention studies, animals were monitored for the onset of symptoms. Animals with detectable protective antigen in serum, a significant increase in temperature, or both received a single intravenous bolus of placebo or Raxibacumab at a dose of either 20 mg per kilogram of body weight or 40 mg per kilogram. The primary end point was...
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Raxibacumab for the Treatment of Inhalational Anthrax
New England Journal of Medicine, 2009Co-Authors: Thi-sau Migone, G. Mani Subramanian, John Zhong, Letha M. Healey, Al Corey, Matt Devalaraja, Larry Lo, Janelle Zimmerman, Stephen Ullrich, Andrew ChenAbstract:Inhalational anthrax caused by Bacillus anthracis is associated with high mortality primarily due to toxin-mediated injury. Raxibacumab is a human IgG1lambda monoclonal antibody directed against protective antigen, a component of the anthrax toxin.
Aaron L. Nelson - One of the best experts on this subject based on the ideXlab platform.
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Development trends for human monoclonal antibody therapeutics
Nature Reviews Drug Discovery, 2010Co-Authors: Aaron L. Nelson, Eugen Dhimolea, Janice M ReichertAbstract:Fully human monoclonal antibodies (mAbs), which have the potential to be less immunogenic than earlier humanized and chimeric mAbs, are the most rapidly growing class of mAbs in clinical development. Here, Reichert and colleagues highlight trends in the development of human mAbs, seven of which have so far gained regulatory approval. Fully human monoclonal antibodies (mAbs) are a promising and rapidly growing category of targeted therapeutic agents. The first such agents were developed during the 1980s, but none achieved clinical or commercial success. Advances in technology to generate the molecules for study — in particular, transgenic mice and yeast or phage display — renewed interest in the development of human mAbs during the 1990s. In 2002, adalimumab became the first human mAb to be approved by the US Food and Drug Administration (FDA). Since then, an additional six human mAbs have received FDA approval: panitumumab, golimumab, canakinumab, ustekinumab, ofatumumab and denosumab. In addition, 3 candidates (Raxibacumab, belimumab and ipilimumab) are currently under review by the FDA, 7 are in Phase III studies and 81 are in either Phase I or II studies. Here, we analyse data on 147 human mAbs that have entered clinical study to highlight trends in their development and approval, which may help inform future studies of this class of therapeutic agents.
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Development trends for human monoclonal antibody therapeutics
Nature Reviews Drug Discovery, 2010Co-Authors: Aaron L. Nelson, Eugen Dhimolea, Janice M ReichertAbstract:Fully human monoclonal antibodies (mAbs) are a promising and rapidly growing category of targeted therapeutic agents. The first such agents were developed during the 1980s, but none achieved clinical or commercial success. Advances in technology to generate the molecules for study - in particular, transgenic mice and yeast or phage display - renewed interest in the development of human mAbs during the 1990s. In 2002, adalimumab became the first human mAb to be approved by the US Food and Drug Administration (FDA). Since then, an additional six human mAbs have received FDA approval: panitumumab, golimumab, canakinumab, ustekinumab, ofatumumab and denosumab. In addition, 3 candidates (Raxibacumab, belimumab and ipilimumab) are currently under review by the FDA, 7 are in Phase III studies and 81 are in either Phase I or II studies. Here, we analyse data on 147 human mAbs that have entered clinical study to highlight trends in their development and approval, which may help inform future studies of this class of therapeutic agents.
Peter Q Eichacker - One of the best experts on this subject based on the ideXlab platform.
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A systematic review and meta-analysis of preclinical trials testing anti-toxin therapies for B. anthracis infection: A need for more robust study designs and results.
PLOS ONE, 2017Co-Authors: Wanying Xu, Yan Li, Lernik Ohanjanian, Dante A. Suffredini, Judith A. Welsh, Peter Q EichackerAbstract:BACKGROUND: B. anthracis anti-toxin agents are approved and included in the Strategic National Stockpile based primarily on animal infection trials. However, in the only anthrax outbreak an approved anti-toxin agent was administered in, survival did not differ comparing recipients and non-recipients, although recipients appeared sicker. OBJECTIVE: Employ a systematic review and meta-analysis to investigate preclinical studies supporting anthrax anti-toxin agents. DATA SOURCE: PubMed, EMBASE, and Scopus. STUDY ELIGIBILITY: Compared survival with an anti-toxin agent versus control in B. anthracis challenged, antibiotic treated animals. STUDY METHODS: Examine model and study design and the effect of anti-toxin agents on relative risk of death(95%CI) (RR). RESULTS: From 9 studies, 29 experiments were analyzed which included 4 species (748 animals) and 5 agents; LFI, AIG, AVP-21D9, Raxibacumab, and ETI-204. Only five experiments were blinded and no experiment included the cardiopulmonary support sick B. anthracis patients receive. Only one agent in a single un-blinded experiment reduced RR significantly [0.45(0.22,0.940]. However, in six studies testing an agent in more than one experiment in the same species, agents had consistent survival effects across experiments [I2 = 0, p≥0.55 in five and I2 = 42%, p = 0.16 in one]. Within each species, agents had effects on the side of benefit; in one study testing AVP-21D9 in mice [0.11(0.01,1.82)] or guinea pigs [0.70(0.48,1.03)]; across eight rabbit studies testing LFI, Raxibacumab, AIG or ETI-204 [0.62(0.45,0.87); I2 = 17.4%, p = 0.29]; and across three monkey studies testing Raxibacumab, AIG or ETI-204 [0.66(0.34,1.27); I2 = 25.3%, p = 0.26]. Across all agents and species, agents decreased RR [0.64(0.52,0.79); I2 = 5.3%, p = 0.39]. LIMITATIONS: Incidence of selective reporting not identifiable. CONCLUSIONS: Although overall significant, individually anti-toxin agents had weak beneficial effects. Lack of study blinding and relevant clinical therapies further weakened studies. Although difficult, preclinical studies with more robust designs and results are warranted to justify the resources necessary to maintain anti-toxin agents in national stockpiles.
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Bacillus anthracis Edema Toxin Increases Fractional Free Water and Sodium Reabsorption in an Isolated Perfused Rat Kidney Model.
Infection and Immunity, 2017Co-Authors: Dharmvir S. Jaswal, Yan Li, Yvonne Fitz, Wanying Xu, Lernik Ohanjanian, Parizad Torabi-parizi, Hannish Sampath-kumar, Peter Q EichackerAbstract:ABSTRACT Bacillus anthracis edema toxin (ET) consists of protective antigen (PA), necessary for host cell toxin uptake, and edema factor (EF), the toxic moiety which increases host cell cyclic AMP (cAMP). Since vasopressin stimulates renal water and sodium reabsorption via increased tubular cell cAMP levels, we hypothesized the ET would also do so. To test this hypothesis, we employed an isolated perfused rat kidney model. Kidneys were isolated and perfused with modified Krebs-Henseleit buffer. Perfusate and urine samples were obtained at baseline and every 10 min over 150 min following the addition of challenges with or without treatments to the perfusate. In kidneys perfused under constant flow or constant pressure, compared to PA challenge (n = 14 or 15 kidneys, respectively), ET (13 or 15 kidneys, respectively) progressively increased urine cAMP levels, water and sodium reabsorption, and urine osmolality and decreased urine output (P ≤ 0.04, except for sodium reabsorption under constant pressure [P = 0.17]). In ET-challenged kidneys, compared to placebo treatment, adefovir, an EF inhibitor, decreased urine cAMP levels, water and sodium reabsorption, and urine osmolality and increased urine output, while Raxibacumab, a PA-directed monoclonal antibody (MAb), decreased urine cAMP levels, free water reabsorption, and urine osmolality and increased urine output (P ≤ 0.03 except for urine output with Raxibacumab [P = 0.17]). Upon immunohistochemistry, aquaporin 2 was concentrated along the apical membrane of tubular cells with ET but not PA, and urine aquaporin 2 levels were higher with ET (5.52 ± 1.06 ng/ml versus 1.51 ± 0.44 ng/ml [means ± standard errors of the means {SEM}; P = 0.0001). Edema toxin has renal effects that could contribute to extravascular fluid collection characterizing anthrax infection clinically.
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Raxibacumab augments hemodynamic support and improves outcomes during shock with B. anthracis edema toxin alone or together with lethal toxin in canines
Intensive Care Medicine Experimental, 2015Co-Authors: Kenneth E Remy, Yan Li, Steven B Solomon, Yvonne Fitz, Amisha V Barochia, Mariam Al-hamad, Mahtab Moayeri, Stephen H Leppla, Peter Q EichackerAbstract:Background Lethal and edema toxin contribute to shock and lethality with Bacillus anthracis . We showed previously in a 96-h sedated canine model that Raxibacumab, a monoclonal antibody against protective antigen, augmented hemodynamic support (HS) and improved survival with lethal toxin challenge. Here we study Raxibacumab further. Using this model, we have now studied Raxibacumab with 24 h edema toxin challenges (Study 1), and lethal and edema toxin challenges together (Study 2). Methods Using our canine model, we have now studied Raxibacumab with 24h edema toxin challenges (Study-1), and lethal and edema toxin challenges together (Study-2). Results In Study 1, compared to no treatment, HS (titrated fluid and norepinephrine) increased mean arterial blood pressure (MAP, p ≤ 0.05) but not survival [0 of 10 (0/10) animals survived in each group] or median survival time [43.8 h (range 16.8 to 80.3) vs. 45.2 h (21.0 to 57.1)]. Compared to HS, HS with Raxibacumab treatment at or 6 h after the beginning of edema toxin increased MAP and survival rate (6/7 and 7/8, respectively) and time [96.0 h (39.5 to 96.0) and 96.0 h (89.5 to 96.0), respectively]; ( p ≤ 0.05). HS with Raxibacumab at 12 h increased MAP ( p ≤ 0.05) but not survival [1/5; 55.3 h (12.6 to 96.0)]. In Study-2, survival rate and time increased with HS and Raxibacumab at 0 h (4/4) or 6 h after (3/3) beginning lethal and edema toxin compared to HS [0/5; 71.5 h (65 to 93)] ( p = 0.01 averaged over Raxibacumab groups). Conclusions Raxibacumab augments HS and improves survival during shock with lethal and edema toxin.
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Raxibacumab augments hemodynamic support and improves outcomes during shock with b anthracis edema toxin alone or together with lethal toxin in canines
Intensive Care Medicine Experimental, 2015Co-Authors: Kenneth E Remy, Yan Li, Steven B Solomon, Yvonne Fitz, Amisha V Barochia, Mahtab Moayeri, Stephen H Leppla, Mariam Alhamad, Peter Q EichackerAbstract:Background Lethal and edema toxin contribute to shock and lethality with Bacillus anthracis. We showed previously in a 96-h sedated canine model that Raxibacumab, a monoclonal antibody against protective antigen, augmented hemodynamic support (HS) and improved survival with lethal toxin challenge. Here we study Raxibacumab further. Using this model, we have now studied Raxibacumab with 24 h edema toxin challenges (Study 1), and lethal and edema toxin challenges together (Study 2).
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Protective Antigen Antibody Augments Hemodynamic Support in Anthrax Lethal Toxin Shock in Canines
The Journal of Infectious Diseases, 2012Co-Authors: Amisha V Barochia, Thi-sau Migone, G. Mani Subramanian, Yan Li, Steven B Solomon, Sally D Bolmer, Peter Q EichackerAbstract:Mortality in patients with shock during the 2001 US anthrax outbreak was high [1, 2]. Although the mechanisms and optimal management of this shock remain unclear, the risk of anthrax persists, as demonstrated by recent cases among injection drug abusers in Europe [3, 4]. Seventeen of 52 patients from this outbreak died, many with progressive shock despite standard intensive care unit (ICU) support. Anthrax bacilli produce 2 toxins: lethal toxin (LT) and edema toxin (ET) [5, 6]. Each is composed of a toxic moiety (lethal factor [LF] or edema factor [EF], respectively) and protective antigen (PA), a component necessary for LF or EF uptake by host cells. LF is a zinc endopeptidase that cleaves mitogen-activated protein kinase kinases (MAPKK), whereas EF is a calmodulin-dependent adenyl cyclase. Of the two, LT is the more lethal and thought to play a central role in the pathogenesis of anthrax shock [7–20]. Despite the contribution of LT-induced shock to the pathogenesis of anthrax, its treatment has received little study. Conventional therapy for septic shock (which would include hemodynamic support with fluid and vasopressor administration titrated to physiologic endpoints like mean arterial pressure) has not been investigated in models of anthrax. In rats, fixed (nontitrated) doses of either normal saline or norepinephrine (NE) administered as 24-hour infusions were beneficial against lipopolysaccharide (LPS) or Escherichia coli challenge, but not LT challenge [20, 21]. Notably, however, inability to titrate these therapies in the LT-challenged rodent model may have produced adverse effects that limited benefit. Besides hemodynamic support, toxin inhibition has also been proposed for the treatment of life-threatening anthrax infection. Both polyclonal (Anthrax Immune Globulin Intravenous [AIGIV], Cangene Corp, Winnipeg, Canada) and monoclonal (Raxibacumab; Human Genome Sciences, Rockville, MD) antibody preparations, directed in part or solely against PA, have been added to the US Strategic National Stockpile. However, whether such preparations have additive benefit when combined with conventionally titrated hemodynamic support is not clear [21–27]. Defining the effects of titrated hemodynamic support, alone or together with protective antigen–directed monoclonal antibody (PA-mAb), for LT-associated shock is important. We previously developed a sedated, instrumented, and mechanically ventilated canine model in which LT, infused over 24 hours to simulate toxin release during infection, produced progressive hypotension and organ dysfunction [16]. We employed this model to investigate the effects of titrated hemodynamic support and PA-directed monoclonal antibody (Raxibacumab) alone or together, for LT-induced shock. Although hemodynamic support was available (if indicated) from the start of toxin infusion, PA-mAb was administered either early at the initiation of toxin (0 hours), or later at 9 or 12 hours to investigate the effect of delayed treatment as might occur clinically.
Eugen Dhimolea - One of the best experts on this subject based on the ideXlab platform.
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Development trends for human monoclonal antibody therapeutics
Nature Reviews Drug Discovery, 2010Co-Authors: Aaron L. Nelson, Eugen Dhimolea, Janice M ReichertAbstract:Fully human monoclonal antibodies (mAbs), which have the potential to be less immunogenic than earlier humanized and chimeric mAbs, are the most rapidly growing class of mAbs in clinical development. Here, Reichert and colleagues highlight trends in the development of human mAbs, seven of which have so far gained regulatory approval. Fully human monoclonal antibodies (mAbs) are a promising and rapidly growing category of targeted therapeutic agents. The first such agents were developed during the 1980s, but none achieved clinical or commercial success. Advances in technology to generate the molecules for study — in particular, transgenic mice and yeast or phage display — renewed interest in the development of human mAbs during the 1990s. In 2002, adalimumab became the first human mAb to be approved by the US Food and Drug Administration (FDA). Since then, an additional six human mAbs have received FDA approval: panitumumab, golimumab, canakinumab, ustekinumab, ofatumumab and denosumab. In addition, 3 candidates (Raxibacumab, belimumab and ipilimumab) are currently under review by the FDA, 7 are in Phase III studies and 81 are in either Phase I or II studies. Here, we analyse data on 147 human mAbs that have entered clinical study to highlight trends in their development and approval, which may help inform future studies of this class of therapeutic agents.
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Development trends for human monoclonal antibody therapeutics
Nature Reviews Drug Discovery, 2010Co-Authors: Aaron L. Nelson, Eugen Dhimolea, Janice M ReichertAbstract:Fully human monoclonal antibodies (mAbs) are a promising and rapidly growing category of targeted therapeutic agents. The first such agents were developed during the 1980s, but none achieved clinical or commercial success. Advances in technology to generate the molecules for study - in particular, transgenic mice and yeast or phage display - renewed interest in the development of human mAbs during the 1990s. In 2002, adalimumab became the first human mAb to be approved by the US Food and Drug Administration (FDA). Since then, an additional six human mAbs have received FDA approval: panitumumab, golimumab, canakinumab, ustekinumab, ofatumumab and denosumab. In addition, 3 candidates (Raxibacumab, belimumab and ipilimumab) are currently under review by the FDA, 7 are in Phase III studies and 81 are in either Phase I or II studies. Here, we analyse data on 147 human mAbs that have entered clinical study to highlight trends in their development and approval, which may help inform future studies of this class of therapeutic agents.
