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Physiological Reviews Jan 1965
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Journal of Pharmaceutical Sciences May 2019Protein therapeutics have drastically changed the landscape of treatment for many diseases by providing a regimen that is highly specific and lacks many off-target... (Review)
Review
Protein therapeutics have drastically changed the landscape of treatment for many diseases by providing a regimen that is highly specific and lacks many off-target toxicities. The clinical utility of many therapeutic proteins has been undermined by the potential development of unwanted immune responses against the protein, limiting their efficacy and negatively impacting its safety profile. This review attempts to provide an overview of immunogenicity of therapeutic proteins, including immune mechanisms and factors influencing immunogenicity, impact of immunogenicity, preclinical screening methods, and strategies to mitigate immunogenicity.
Topics: Animals; Antibodies; Antibody Formation; Humans; Proteins
PubMed: 30599169
DOI: 10.1016/j.xphs.2018.12.014 -
Pediatriia Oct 1964
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MAbs 2020The origins of the various elements in the human antibody repertoire have been and still are subject to considerable uncertainty. Uncertainty in respect of whether the... (Review)
Review
The origins of the various elements in the human antibody repertoire have been and still are subject to considerable uncertainty. Uncertainty in respect of whether the various elements have always served a specific defense function or whether they were co-opted from other organismal roles to form a crude naïve repertoire that then became more complex as combinatorial mechanisms were added. Estimates of the current size of the human antibody naïve repertoire are also widely debated with numbers anywhere from 10 million members, based on experimentally derived numbers, to in excess of one thousand trillion members or more, based on the different sequences derived from theoretical combinatorial calculations. There are questions that are relevant at both ends of this number spectrum. At the lower bound it could be questioned whether this is an insufficient repertoire size to counter all the potential antigen-bearing pathogens. At the upper bound the question is rather simpler: How can any individual interrogate such an astronomical number of antibody-bearing B cells in a timeframe that is meaningful? This review evaluates the evolutionary aspects of the adaptive immune system, the calculations that lead to the large repertoire estimates, some of the experimental evidence pointing to a more restricted repertoire whose variation appears to derive from convergent 'structure and specificity features', and includes a theoretical model that seems to support it. Finally, a solution that may reconcile the size difference anomaly, which is still a hot subject of debate, is suggested.
Topics: Antibody Formation; Humans
PubMed: 32097086
DOI: 10.1080/19420862.2020.1729683 -
Progress in Allergy 1967
Review
Topics: Animals; Antibody Formation; Child; Female; Guinea Pigs; Humans; Kinetics; Mice; Rabbits; Rats; Sheep
PubMed: 5333338
DOI: No ID Found -
Methods in Medical Research 1964
Review
Topics: Antibody Formation; Research Design; Tissue Culture Techniques
PubMed: 14284939
DOI: No ID Found -
Saishin Igaku. Modern Medicine May 1966
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Revue Medicale de La Suisse Romande May 1964
Review
Topics: Antibody Formation; Immune System Phenomena; Immunity; Radiation Effects; Transplantation
PubMed: 14151594
DOI: No ID Found -
Plastic and Reconstructive Surgery Oct 1961
Topics: Antibody Formation; Enzymes; Transplantation Immunology
PubMed: 14005927
DOI: No ID Found -
Annual Review of Medicine 1967
Review
Topics: Animals; Antibody Formation; Antigen-Antibody Reactions; Rats
PubMed: 5337538
DOI: 10.1146/annurev.me.18.020167.000501