Immunogenicity of protein therapeutics: The key causes, consequences and challenges

doi:10.4161/self.1.4.13904

. 2010 Oct;1(4):314-322.

doi: 10.4161/self.1.4.13904.

Immunogenicity of protein therapeutics: The key causes, consequences and challenges

Matthew P Baker¹, Helen M Reynolds, Brooke Lumicisi, Christine J Bryson

Affiliations

PMID: 21487506
PMCID: PMC3062386
DOI: 10.4161/self.1.4.13904

Immunogenicity of protein therapeutics: The key causes, consequences and challenges

Matthew P Baker et al. Self Nonself. 2010 Oct.

. 2010 Oct;1(4):314-322.

doi: 10.4161/self.1.4.13904.

Authors

Matthew P Baker¹, Helen M Reynolds, Brooke Lumicisi, Christine J Bryson

Affiliation

¹ Antitope Ltd.; Babraham Research Campus; Babraham, Cambridge UK.

PMID: 21487506
PMCID: PMC3062386
DOI: 10.4161/self.1.4.13904

Abstract

The immunogenicity of protein therapeutics has so far proven to be difficult to predict in patients, with many biologics inducing undesirable immune responses directed towards the therapeutic resulting in reduced efficacy, anaphylaxis and occasionally life threatening autoimmunity. The most common effect of administrating an immunogenic protein therapeutic is the development of a high affinity anti-therapeutic antibody response. Furthermore, it is clear from clinical studies that protein therapeutics derived from endogenous human proteins are capable of stimulating undesirable immune responses in patients, and as a consequence, the prediction and reduction of immunogenicity has been the focus of intense research. This review will outline the principle causes of the immunogenicity in protein therapeutics, and describe the development of pre-clinical models that can be used to aid in the prediction of the immunogenic potential of novel protein therapeutics prior to administration in man.

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References

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[1] Bertolotto A, Malucchi S, Sala A, Orefice G, Carrieri PB, Capobianco M, et al. Differential effects of three interfeorn betas on neutralising antibodies in patients with multiple sclerosis: a follow up study in an independent laboratory. J Neurol Neurosurg Psychiatry. 2002;73:148–153. - PMC - PubMed

[2] Bertolotto A, Malucchi S, Sala A, Orefice G, Carrieri PB, Capobianco M, et al. Differential effects of three interfeorn betas on neutralising antibodies in patients with multiple sclerosis: a follow up study in an independent laboratory. J Neurol Neurosurg Psychiatry. 2002;73:148–153. - PMC - PubMed

[3] Bertolotto A, Sala A, Malucchi S, Marnetto F, Caldano M, Di Sapio A, et al. Biological activity of interferon betas in patients with multiple sclerosis is affected by treatment regimen and neutralising antibodies. J Neurol Neurosurg Psychiatry. 2004;75:1294–1299. - PMC - PubMed

[4] Bertolotto A, Sala A, Malucchi S, Marnetto F, Caldano M, Di Sapio A, et al. Biological activity of interferon betas in patients with multiple sclerosis is affected by treatment regimen and neutralising antibodies. J Neurol Neurosurg Psychiatry. 2004;75:1294–1299. - PMC - PubMed

[5] Cook SD, Quinless JR, Jotkowitz A, Beaton P. Serum IFN neutralizing antibodies and neopterin levels in a cross-section of MS patients. Neurology. 2001;57:1080–1084. - PubMed

[6] Cook SD, Quinless JR, Jotkowitz A, Beaton P. Serum IFN neutralizing antibodies and neopterin levels in a cross-section of MS patients. Neurology. 2001;57:1080–1084. - PubMed

[7] Ryff JC. Clinical investigation of the immunogenicity of interferon-alpha2a. J Interferon Cytokine Res. 1997;17:29–33. - PubMed

[8] Ryff JC. Clinical investigation of the immunogenicity of interferon-alpha2a. J Interferon Cytokine Res. 1997;17:29–33. - PubMed

[9] Von Wussow P, Hehlmann R, Hochhaus T, Jakschies D, Nolte KU, Prümmer O, et al. Roferon (rIFNalpha2a) is more immunogenic than intron A (rIFNalpha2b) in patients with chronic myelogenous leukemia. J Interferon Res. 1994;14:217–219. - PubMed

[10] Von Wussow P, Hehlmann R, Hochhaus T, Jakschies D, Nolte KU, Prümmer O, et al. Roferon (rIFNalpha2a) is more immunogenic than intron A (rIFNalpha2b) in patients with chronic myelogenous leukemia. J Interferon Res. 1994;14:217–219. - PubMed

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Immunogenicity of protein therapeutics: The key causes, consequences and challenges

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Immunogenicity of protein therapeutics: The key causes, consequences and challenges

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