Potential cross-reactivity of monoclonal antibodies against clinically relevant mycobacteria

Flores-Moreno, Karen; Celis-Meneses, J S; Meneses-Ruiz, Dulce María; Castillo-Rodal, Antonia Isabel; Orduña, Patricia; Montiel, B A; López-Vidal, Yolanda

doi:10.1111/cei.12309

Cited by 5 publications

(10 citation statements)

References 22 publications

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“…Specifically, PET scans would look for increased activity in the posterior cingulate and temporoparietal regions, which show significantly lessened metabolism in the AD brain when compared to a healthy control [89,90]. Additionally, the use of biomarker reduction as an indicator of target engagement, though superficially logical, is particularly inadequate when concerning Aβ-targeting immunotherapies, due to the potential for antibody cross-reactivity (though cross-reactivity is much less likely in clinically useful monoclonal strategies than other antibody-based therapeutics) [91,92]. In other words, the reduction of toxic Aβ in response to treatment with a monoclonal antibody does not summarily imply the binding of such antibody to Aβ itself or to the correct epitope [91][92][93].…”

Section: Potential Causes Of Trialmentioning

confidence: 99%

“…Additionally, the use of biomarker reduction as an indicator of target engagement, though superficially logical, is particularly inadequate when concerning Aβ-targeting immunotherapies, due to the potential for antibody cross-reactivity (though cross-reactivity is much less likely in clinically useful monoclonal strategies than other antibody-based therapeutics) [91,92]. In other words, the reduction of toxic Aβ in response to treatment with a monoclonal antibody does not summarily imply the binding of such antibody to Aβ itself or to the correct epitope [91][92][93]. The antibody may in fact be binding to an unintended target that, due to a secondary mechanism, results in the reduction of Aβ.…”

Section: Potential Causes Of Trialmentioning

confidence: 99%

“…The antibody may in fact be binding to an unintended target that, due to a secondary mechanism, results in the reduction of Aβ. However, any unintended binding may have additional side effects that complicate trial results [91,93].…”

Section: Potential Causes Of Trialmentioning

confidence: 99%

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Clinical Trials in Alzheimer’s Disease: A Hurdle in the Path of Remedy

Oxford

Stewart

Rohn

2020

International Journal of Alzheimer's Disease

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Human clinical trials seek to ameliorate the disease states and symptomatic progression of illnesses that, as of yet, are largely untreatable according to clinical standards. Ideally, clinical trials test “disease-modifying drugs,” i.e., therapeutic agents that specifically modify pathological features or molecular bases of the disease and would presumably have a large impact on disease progression. In the case of Alzheimer’s disease (AD), however, this approach appears to have stalled progress in the successful development of clinically useful therapies. For the last 25 years, clinical trials involving AD have centered on beta-amyloid (Aβ) and the Aβ hypothesis of AD progression and pathology. According to this hypothesis, the progression of AD begins following an accumulation of Aβ peptide, leading to eventual synapse loss and neuronal cell death: the true overriding pathological feature of AD. Clinical trials arising from the Aβ hypothesis target causal steps in the pathway in order to reduce the formation of Aβ or enhance clearance, and though agents have been successful in this aim, they remain unsuccessful in rescuing cognitive function or slowing cognitive decline. As such, further use of resources in the development of treatment options for AD that target Aβ, its precursors, or its products should be reevaluated. The purpose of this review was to give an overview of how human clinical trials are conducted in the USA and to assess the results of recent failed trials involving AD, the majority of which were based on the Aβ hypothesis. Based on these current findings, it is suggested that lowering Aβ is an unproven strategy, and it may be time to refocus on other targets for the treatment of this disease including pathological forms of tau.

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Section: Potential Causes Of Trialmentioning

confidence: 99%

Section: Potential Causes Of Trialmentioning

confidence: 99%

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Clinical Trials in Alzheimer’s Disease: A Hurdle in the Path of Remedy

Oxford

Stewart

Rohn

2020

International Journal of Alzheimer's Disease

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“…The most striking aspects of aptamers are heightened epitope affinity and specificity. Whereas, mAbs still suffer from cross-reactivity for closely related protein epitopes (Flores-Moreno et al, 2014). Immunogenicity has been uncovered as a serious drawback of mAbs used as therapies -host immune response can create antibodies against the administered therapeutic mAbs as even the purified versions could have residues of animal proteins (Harding et al, 2010;Knezevic, Kang, & Thorpe, 2015).…”

Section: How Are Aptamers Different From Antibodies?mentioning

confidence: 99%

Fluorescent aptamers for detection and treatment of pathogenic bacteria and cancer

Sharma

Ramena

2021

Fluorescent Probes

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“…CLUSTAL W served for calculating the rate of local and global aminoacidic conservation rate [52]. We selected this software due to its large utilization and proven validity [53][54][55][56][57]. The aminoacidic conservation rate is the result of the sequence alignment of the amino acids of two proteins that are more or less conserved (changes in the amino acid sequence) in different species.…”

Section: Comparative Evolutionary Genomicmentioning

confidence: 99%

Hippocampal Pruning as a New Theory of Schizophrenia Etiopathogenesis

2015

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Pruning in neurons has been suggested to be strongly involved in Schizophrenia's (SKZ) etiopathogenesis in recent biological, imaging, and genetic studies. We investigated the impact of protein-coding genes known to be involved in pruning, collected by a systematic literature research, in shaping the risk for SKZ in a case-control sample of 9,490 subjects (Psychiatric Genomics Consortium). Moreover, their modifications through evolution (humans, chimpanzees, and rats) and subcellular localization (as indicative of their biological function) were also investigated. We also performed a biological pathways (Gene Ontology) analysis. Genetics analyses found four genes (DLG1, NOS1, THBS4, and FADS1) and 17 pathways strongly involved in pruning and SKZ in previous literature findings to be significantly associated with the sample under analysis. The analysis of the subcellular localization found that secreted genes, and so regulatory ones, are the least conserved through evolution and also the most associated with SKZ. Their cell line and regional brain expression analysis found that their areas of primary expression are neuropil and the hippocampus, respectively. At the best of our knowledge, for the first time, we were able to describe the SKZ neurodevelopmental hypothesis starting from a single biological process. We can also hypothesize how alterations in pruning fine regulation and orchestration, strongly related with the evolutionary newest (and so more sensitive) secreted proteins, may be of particular relevance in the hippocampus. This early alteration may lead to a mis-structuration of neural connectivity, resulting in the different brain alteration that characterizes SKZ patients.

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Potential cross-reactivity of monoclonal antibodies against clinically relevant mycobacteria

Abstract: Summary Tuberculosis is a disease caused by the

Cited by 5 publications

References 22 publications

Clinical Trials in Alzheimer’s Disease: A Hurdle in the Path of Remedy

Clinical Trials in Alzheimer’s Disease: A Hurdle in the Path of Remedy

Fluorescent aptamers for detection and treatment of pathogenic bacteria and cancer

Hippocampal Pruning as a New Theory of Schizophrenia Etiopathogenesis

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