Recombinant proteins immune responses

Anti-human recombinant protein antibody response may alter pharmacokinetics, neutralise biological effects, cause immune-complex lesions, or have no relevant consequence in animals. 

Based on the above principles, it might be assumed that a therapeutic protein obtained by direct extraction from human sources (e.g. some antibody preparations) or produced via recombinant expression of a human gene/cDNA sequence (e.g. recombinant human hormones or cytokines) would be non-immunogenic in humans whereas foreign therapeutic proteins (e.g. non-engineered monoclonal antibodies) would stimulate a human immune response. This general principle holds in many cases, but not all. So why do therapeutic proteins of human amino acid sequences have the potential to trigger an immune response Potential reasons can include ... 

Most of the recombinant subunit vaccines tested in the first half of this decade employed gp 120 or gp 160 expressed in yeast, insect or mammalian (mainly CHO) cell lines. Eukaryotic systems facilitate glycosylation of the protein products. Like all subunit vaccines, these stimulate a humoral-based immune response but fail to elicit a strong T-cell response. The failure to elicit a cell-based... 

Dean, J.H., Comacoff, J.B., Labrie, T. and Barbolt, T.A. (1990). Assessment of immune responses in rodents and non-human primates—Implications in preclinical evaluation of proteins. In Preclinical Evaluation of Peptides and Recombinant Proteins, (Sundwall, A. et al., Eds.) Malmo. Skogs Grafiska AB, Stockholm, Sweden, pp. 23-34. 

Vaccines made with recombinant proteins marshal an immune response to specific viruses to treat or prevent disease. Vaccines to prevent infection with the liver-damaging hepatitis viruses (Twinrix , Recombivax HB , and Engerix-B ) include a recombinant version of a hepatitis virus B protein. Recombinant hepatitis B protein is also included in some combination vaccines given to children. Comvax also includes a recombinant flu virus protein. 

Several proteins that stimulate subsets of lymphocytes involved in various aspects of the immune response are now produced by recombinant DNA techniques. The pharmacology of these lymphokines as potential anticancer agents is being investigated. Interleukin (IL) 2, originally described as a T-cell growth factor, induces the production of cytotoxic lymphocytes (lymphokine-activated killer cells, or LAK cells). IL-2 produces remissions in 10 to 20% of patients with melanoma or renal cell carcinoma when infused at high doses either alone or with lymphocytes that were previously harvested from the patient and incubated with IL-2 in vitro. 

IgE reactivity to these V-glycans have been studied and compared with IgE reactivity to a number of glycoproteins of known primary structures. These differences can induce undesirable immune responses in mammals and/or reduce the activity of recombinant proteins. 

While it is generally true that recombinant proteins containing amino-acid sequences identical to those of humans are less immunogenic than mouse-based recombinant proteins, human-based recombinant proteins can, because of their size, elicit immune responses on repeated administration. The impact of immuno-genicity on pharmacologic and toxic effects is only now beginning to be adequately appreciated. 

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