Theoretical and Practical Aspects of Antigenized Antibodies

Zanetti, Maurizio; Rossi, F; Lanza, Paola; Filaci, Gilberto; Lee, Richard H.; Billetta, Rosario

doi:10.1111/j.1600-065x.1992.tb01524.x

Cited by 16 publications

(11 citation statements)

References 102 publications

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“…Owing to the fact that animals respond to isologous and autologous idiotypic determinants (40,41), immunization by antibodies antigenized with discrete stretches of somatic cell receptors is also a way to circumvent unresponsiveness to self proteins (modified self) and induce anti-receptor immunity ofexquisite molecular and biological specificity. The present demonstration validates antibody mimicry as a viable concept and points to a different direction of study in the structure-function of antibodies, including practical applications for antigenized antibodies (42).…”

supporting

confidence: 69%

Active immunity against the CD4 receptor by using an antibody antigenized with residues 41-55 of the first extracellular domain.

Lanza

Billetta

Антоненко

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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Active immunity against the CD4 receptor by using an antibody antigenized with residues 41-55 of the first extracellular domain ABSTRACTUsing the process of "antibody antigenization," we engineered two antibody molecules carrying in the third complementarity-determining region of the heavy chain variable domain a 7-mer or a 15-mer peptide epitope ofthe first extraceliular domain (D1) of human CD4 receptor-namely, Ser-Phe-Leu-Thr-Lys-Gly-Pro-Ser (SFLTKGPS; positions 42 through 49) and Gly-Ser-Phe-Leu-Thr-Lys-Gly-Pro-Ser-LysLeu-Asn-Asp-Arg-Ala (GSFLTKGPSKLNDRA; positions 41 through 55). These amino acid sequences are contained in the consensus binding site for the human immunodeficiency virus (HIV) on CD4 receptor. Both antigenized antibodies (AgAbs) bound recombinant gpl20 and were recognized by a prototype monoclonal antibody to CD4 whose binding site is within amino acid residues 41-55. AgAbs were then used as immunogens in rabbits and mice to elicit a humoral response against CD4.

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supporting

confidence: 69%

Active immunity against the CD4 receptor by using an antibody antigenized with residues 41-55 of the first extracellular domain.

Lanza

Billetta

Антоненко

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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“…For instance, somatic transgene immunization can be used to induce immunity in selected circumstances against: (i) self idiotypes in patients with nonsecreting chronic lymphocytic leukemia (53); (ii) Ig genes chimerized with self-receptors, cytokines, or growth factors (54-57); and (iii) self or foreign antigen peptides coded in the CDRs of the transgene (58). It cannot be excluded that a similar approach may become useful in gene therapy and replacement to achieve good levels of secretion for a variety of proteins of biological or pharmacological interest.…”

Section: Discussionmentioning

confidence: 99%

In vivorole of B lymphocytes in somatic transgene immunization

Xiong

Gerloni

Zanetti

1997

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

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Immunity generated by in vivo inoculation of plasmid DNA is a straightforward and potentially valuable new approach to immunization. Little is known about the type of cells involved, the various immunological aspects, and the destiny of the transgene. In this report, we describe a system in which immunity is the result of in vivo targeting of B lymphocytes. This was accomplished using plasmid DNA encoding an immunoglobulin heavy-chain gene under the control of immunoglobulin promoter and enhancer elements. We show persistence of the transgene in splenic B lymphocytes for at least 3 months, i.e., the average life span of long-lived B lymphocytes in the mouse. The transgene could not be detected in any other lymphoid or nonlymphoid organs over a period of 6 months. We also established that the transgene is integrated in the host DNA. These studies bring new understanding to the events underlying the in vivo use of plasmid DNA. Moreover, the characteristics of this new approach make somatic transgene immunization a model system to study the immunogenicity of endogenous antigens in adult animals.

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“…Since the mutagenesis of CDRs allows antigen binding affinity engineering and specificity mapping at the level of individual amino acids, it follows that residues elsewhere in CDRs but outside the antigen combining site may be substituted, with little consequence for the overall antibody structure. This concept has been named 'antibody antigenisation' [3,101], where portions of CDRs are substituted with sequences either from CDRs of other mAbs or from non-antibody proteins. The concept has been exploited in the example described in patent WO9925378, where peptides corresponding to the receptor-binding portion of the protein bradykinin have been grafted into the CDRs of a known mAb.…”

Section: Introductionmentioning

confidence: 99%

Site-specific structural modification of monoclonal antibodies for therapeutic application

2000

Expert Opinion on Therapeutic Patents

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Theoretical and Practical Aspects of Antigenized Antibodies

Cited by 16 publications

References 102 publications

Active immunity against the CD4 receptor by using an antibody antigenized with residues 41-55 of the first extracellular domain.

Active immunity against the CD4 receptor by using an antibody antigenized with residues 41-55 of the first extracellular domain.

In vivorole of B lymphocytes in somatic transgene immunization

Site-specific structural modification of monoclonal antibodies for therapeutic application

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