Monoclonal antibodies as anti-infective products: a promising future?

Pelfrene, Eric; Mura, María Stella; Sanches, A. Cavaleiro; Cavaleri, Marco

doi:10.1016/j.cmi.2018.04.024

Cited by 68 publications

(51 citation statements)

References 61 publications

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“…The vast majority of FDA-approved mAbs have been developed to treat one or more of a wide range of cancers and inflammatory diseases. A few, however, have been approved for use in infectious disease settings, such as palivizumab for respiratory syncytial virus and ibalizumab-uiyk for the treatment of multidrug-resistant HIV-1 infection [15]. The potential of mAb use for protection against viral diseases has increasingly been raised, partly due to the recent surge in clinically approved mAbs in other disease areas as well as advancements in mAb technologies in general [15,16].…”

Section: Antibodies As Drugs For Fighting Infectious Diseasementioning

confidence: 99%

“…A few, however, have been approved for use in infectious disease settings, such as palivizumab for respiratory syncytial virus and ibalizumab-uiyk for the treatment of multidrug-resistant HIV-1 infection [15]. The potential of mAb use for protection against viral diseases has increasingly been raised, partly due to the recent surge in clinically approved mAbs in other disease areas as well as advancements in mAb technologies in general [15,16]. In acute settings, such as in response to an EID or bioterrorism, where the speed of conferring protection is of particular value, the potential for mAb use has been widely acknowledged [15,17].…”

Section: Antibodies As Drugs For Fighting Infectious Diseasementioning

confidence: 99%

“…The potential of mAb use for protection against viral diseases has increasingly been raised, partly due to the recent surge in clinically approved mAbs in other disease areas as well as advancements in mAb technologies in general [15,16]. In acute settings, such as in response to an EID or bioterrorism, where the speed of conferring protection is of particular value, the potential for mAb use has been widely acknowledged [15,17]. In contrast to vaccines, in which protection takes several days to a few weeks to fully develop, mAbs have the ability to provide near instantaneous protection following administration [17,18].…”

Section: Antibodies As Drugs For Fighting Infectious Diseasementioning

confidence: 99%

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In vivo expressed biologics for infectious disease prophylaxis: rapid delivery of DNA-based antiviral antibodies

Andrews

Huang

et al. 2020

Emerging Microbes & Infections

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With increasing frequency, humans are facing outbreaks of emerging infectious diseases (EIDs) with the potential to cause significant morbidity and mortality. In the most extreme instances, such outbreaks can become pandemics, as we are now witnessing with COVID-19. According to the World Health Organization, this new disease, caused by the novel coronavirus SARS-CoV-2, has already infected more than 10 million people worldwide and led to 499,913 deaths as of 29 June, 2020. How high these numbers will eventually go depends on many factors, including policies on travel and movement, availability of medical support, and, because there is no vaccine or highly effective treatment, the pace of biomedical research. Other than an approved antiviral drug that can be repurposed, monoclonal antibodies (mAbs) hold the most promise for providing a stopgap measure to lessen the impact of an outbreak while vaccines are in development. Technical advances in mAb identification, combined with the flexibility and clinical experience of mAbs in general, make them ideal candidates for rapid deployment. Furthermore, the development of mAb cocktails can provide a faster route to developing a robust medical intervention than searching for a single, outstanding mAb. In addition, mAbs are well-suited for integration into platform technologies for delivery, in which minimal components need to be changed in order to be redirected against a novel pathogen. In particular, utilizing the manufacturing and logistical benefits of DNA-based platform technologies in order to deliver one or more antiviral mAbs has the potential to revolutionize EID responses.

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Section: Antibodies As Drugs For Fighting Infectious Diseasementioning

confidence: 99%

Section: Antibodies As Drugs For Fighting Infectious Diseasementioning

confidence: 99%

Section: Antibodies As Drugs For Fighting Infectious Diseasementioning

confidence: 99%

See 1 more Smart Citation

In vivo expressed biologics for infectious disease prophylaxis: rapid delivery of DNA-based antiviral antibodies

Andrews

Huang

et al. 2020

Emerging Microbes & Infections

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“…32,33 While effective, antibodies can be challenging to produce and globally distribute at scale. 34,35 Alternative compelling strategies include employing synthetic molecules that bind bacterial surface proteins 36,37 or peptidoglycans, 36,38 and present haptens so as to recruit the native immune system to promote bacterial clearance. Other synthetic approaches include metabolically incorporating nonnative haptens into bacterial surface components.…”

Section: Introductionmentioning

confidence: 99%

Antibody-recruiting protein-catalyzed capture agents to combat antibiotic-resistant bacteria

et al. 2020

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“…(26,27) While effective, antibodies can be challenging to produce and globally distribute at scale. (28,29) Alternative compelling strategies include employing synthetic molecules that bind bacterial surface proteins (30,31) or peptidoglycans, (30,32) and present haptens so as to recruit the native immune system to promote bacterial clearance. Other synthetic approaches include metabolically incorporating non-native haptens into bacterial surface components.…”

Section: Introductionmentioning

confidence: 99%

Antibody-Recruiting Protein-Catalyzed Capture Agents to Combat Antibiotic-Resistant Bacteria

Idso

Akhade

Arrieta-Ortiz

et al. 2019

Preprint

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Antibiotic resistant infections are projected to cause over 10 million deaths by 2050, yet the development of new antibiotics has slowed. This points to an urgent need for methodologies for the rapid development of antibiotics against emerging drug resistant pathogens. We report on a generalizable combined computational and synthetic approach, called antibody-recruiting proteincatalyzed capture agents (AR-PCCs), to address this challenge. We applied the combinatorial PCC technology to identify macrocyclic peptide ligands against highly conserved surface protein epitopes of carbapenem-resistant Klebsiella pneumoniae, an opportunistic gram-negative pathogen with drug resistant strains. Multi-omic data combined with bioinformatic analyses identified epitopes of the highly expressed MrkA surface protein of K. pneumoniae for targeting in PCC screens. The top-performing ligand exhibited high-affinity (EC50~50 nM) to full-length MrkA, and selectively bound to MrkAexpressing K. pneumoniae, but not to other pathogenic bacterial species. AR-PCCs conjugated with immunogens promoted antibody recruitment to K. pneumoniae, leading to phagocytosis and phagocytic killing by macrophages. The rapid development of this highly targeted antibiotic implies that the integrated computational and synthetic toolkit described here can be used for the accelerated production of antibiotics against drug resistant bacteria. resistant K. pneumoniae, and that the basic technology might provide a route towards drugging "undruggable" pathogenic bacteria. Results and DiscussionMulti-omic analyses to select target a protein on K. pneumoniae Here we describe the algorithm used to identify protein targets, and epitopes on those targets, for drugging K. pneumoniae using AR-PCCs. Traditional drugging strategies tend to rely on disrupting the function of, for example, an enzyme by competing for occupancy within a strategic hydrophobic binding pocket. Our requirements are very different. Instead, favorable aspects of target proteins are high expression levels on only the pathogen of interest, plus localization of that protein to the outer membrane or extracellular space of the pathogen. Further, once such a target protein is identified, there are additional considerations regarding which epitopes of that protein present the greatest opportunities for exploiting AR-PCCs. The flow diagram in Figure 2A delineates the strategy for identifying MrkA as an ideal target protein. Protein expression levels can vary across environments and growth phases, so we analyzed the transcriptional data reported by Guilhen et al(40) to identify proteins

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Monoclonal antibodies as anti-infective products: a promising future?

Cited by 68 publications

References 61 publications

In vivo expressed biologics for infectious disease prophylaxis: rapid delivery of DNA-based antiviral antibodies

In vivo expressed biologics for infectious disease prophylaxis: rapid delivery of DNA-based antiviral antibodies

Antibody-recruiting protein-catalyzed capture agents to combat antibiotic-resistant bacteria

Antibody-Recruiting Protein-Catalyzed Capture Agents to Combat Antibiotic-Resistant Bacteria

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