Back to the future: recombinant polyclonal antibody therapeutics

Wang, Xianzhe; Coljee, Vincent W.; Maynard, Jennifer A.

doi:10.1016/j.coche.2013.08.005

Cited by 28 publications

(24 citation statements)

References 79 publications

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“…Antibody therapy is used to treat a variety of disease, from auto immune/inflammatory, to cancer, to infectious disease [74]. The majority of antibody therapies are monoclonal antibodies (mAb), with polyclonal antibodies (pAb) becoming more heavily investigated, especially for cancer therapy [75]. While mAbs target one specific epitope of an antigen, pAbs can target multiple epitopes and therefore hold the potential for increased efficacy [76].…”

Section: New Technologies In Drug Developmentmentioning

confidence: 99%

Technological advances in precision medicine and drug development

Maggi

Patterson

Montagna

2016

Expert Review of Precision Medicine and Drug Development

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New technologies are rapidly becoming available to expand the arsenal of tools accessible for precision medicine and to support the development of new therapeutics. Advances in liquid biopsies, which analyze cells, DNA, RNA, proteins, or vesicles isolated from the blood, have gained particular interest for their uses in acquiring information reflecting the biology of tumors and metastatic tissues. Through advancements in DNA sequencing that have merged unprecedented accuracy with affordable cost, personalized treatments based on genetic variations are becoming a real possibility. Extraordinary progress has been achieved in the development of biological therapies aimed to even further advance personalized treatments. We provide a summary of current and future applications of blood based liquid biopsies and how new technologies are utilized for the development of biological therapeutic treatments. We discuss current and future sequencing methods with an emphasis on how technological advances will support the progress in the field of precision medicine.

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Section: New Technologies In Drug Developmentmentioning

confidence: 99%

Technological advances in precision medicine and drug development

Maggi

Patterson

Montagna

2016

Expert Review of Precision Medicine and Drug Development

View full text Add to dashboard Cite

show abstract

“…Characterisation of the affinity of antibodies for its target species is important in many medical applications including passive immunity from anti-sera, humanised antibodies for immunotherapy [1,2] and chemotherapy [3,4] and in assessing the immune response of an animal for vaccine candidate screening [5,6]. An antibody's affinity for its target antigen is controlled by interactions at the Fab binding site [5,7] and, ideally, should not have any cross-reactivity with accidental epitopes within the blood or tissue proteome of the patient.…”

Section: Introductionmentioning

confidence: 99%

Label-free Fab and Fc affinity/avidity profiling of the antibody complex half-life for polyclonal and monoclonal efficacy screening

et al. 2015

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A unified approach to affinity screening for Fab and Fc interactions of an antibody for its antigen and FcγR receptor has been developed. An antigen array is used for the Fab affinity and cross-reactivity screening and protein A/G proxy is the FcγR receptor. The affinities are derived using a simple 1:1 binding model with a consistent error analysis. The association and dissociation kinetics are measured over optimised times for accurate determination. The Fab/Fc affinities are derived for ten antibodies: mAb-actin (mouse), pAb-BSA (sheep), pAb-collagen V (rabbit), pAb-CRP (goat), mAb-F1 (mouse), mAbs (mouse) 7.3, 12.3, 29.3, 36.3 and 46.3 raised against LcrV in Yersinia pestis. The rate of the dissociation of antigen-antibody complexes relates directly to their immunological function as does the Fc-FcγR complex and a new half-life plot has been defined with a Fab/Fc half-life range of 17-470 min. The upper half-life value points to surface avidity. Two antibodies that are protective as an immunotherapy define a Fab half-life >250 min and an Fc half-life >50 min as characteristics of ideal interactions which can form the basis of an antibody screen for immunotherapy.

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“…Indeed, the benefits of using polyclonal antibody preparations to treat disease in therapeutic settings are just beginning to be realized (22). In addition, recent discovery of the remarkable effects of heavy-chain constant regions (C H ) in allosterically modulating the affinity and specificity of identical variable (V) regions is fueling intensive new investigation into isotype-specific effects of antibodies (23)(24)(25)(26)(27)(28)(29)(30).…”

mentioning

confidence: 99%

Broadly Neutralizing Anti-Influenza Virus Antibodies: Enhancement of Neutralizing Potency in Polyclonal Mixtures and IgA Backbones

Mullarkey

Duty

et al. 2015

J Virol

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Current influenza virus vaccines rely upon the accurate prediction of circulating virus strains months in advance of the actual influenza season in order to allow time for vaccine manufacture. Unfortunately, mismatches occur frequently, and even when perfect matches are achieved, suboptimal vaccine efficacy leaves several high-risk populations vulnerable to infection. However, the recent discovery of broadly neutralizing antibodies that target the hemagglutinin (HA) stalk domain has renewed hope that the development of "universal" influenza virus vaccines may be within reach. Here, we examine the functions of influenza A virus hemagglutinin stalk-binding antibodies in an endogenous setting, i.e., as polyclonal preparations isolated from human sera. Relative to monoclonal antibodies that bind to the HA head domain, the neutralization potency of monoclonal stalk-binding antibodies was vastly inferior in vitro but was enhanced by several orders of magnitude in the polyclonal context. Furthermore, we demonstrated a surprising enhancement in IgA-mediated HA stalk neutralization relative to that achieved by antibodies of IgG isotypes. Mechanistically, this could be explained in two ways. Identical variable regions consistently neutralized virus more potently when in an IgA backbone compared to an IgG backbone. In addition, HA-specific memory B cells isolated from human peripheral blood were more likely to be stalk specific when secreting antibodies of IgA isotypes compared to those secreting IgG. Taken together, our data provide strong evidence that HA stalk-binding antibodies perform optimally when in a polyclonal context and that the targeted elicitation of HA stalk-specific IgA should be an important consideration during "universal" influenza virus vaccine design. IMPORTANCEInfluenza viruses remain one of the most worrisome global public health threats due to their capacity to cause pandemics. While seasonal vaccines fail to protect against the emergence of pandemic strains, a new class of broadly neutralizing antibodies has been recently discovered and may be the key to developing a "universal" influenza virus vaccine. While much has been learned about the biology of these antibodies, most studies have focused only on monoclonal antibodies of IgG subtypes. However, the study of monoclonal antibodies often fails to capture the complexity of antibody functions that occur during natural polyclonal responses. Here, we provide the first detailed analyses of the biological activity of these antibodies in polyclonal contexts, comparing both IgG and IgA isotypes isolated from human donors. The striking differences observed in the functional properties of broadly neutralizing antibodies in polyclonal contexts will be essential for guiding design of "universal" influenza virus vaccines and therapeutics. I nfluenza A viruses (IAVs) remain one of the most pressing global public health concerns due to their widespread distribution, rapid evolution, and potential for reassortment (1). These traits contribute to the abil...

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Back to the future: recombinant polyclonal antibody therapeutics

Cited by 28 publications

References 79 publications

Technological advances in precision medicine and drug development

Technological advances in precision medicine and drug development

Label-free Fab and Fc affinity/avidity profiling of the antibody complex half-life for polyclonal and monoclonal efficacy screening

Broadly Neutralizing Anti-Influenza Virus Antibodies: Enhancement of Neutralizing Potency in Polyclonal Mixtures and IgA Backbones

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