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Antibodies pp 199-215 | Cite as

Future Prospects in Antibody Engineering and Therapy

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Abstract

Since their discovery by Köhler and Milstein (1975), monoclonal antibodies (mAbs) have been intensively engineered to optimise their therapeutic properties. Although the first mAb to be approved for a clinical use was a murine antibody (OKT3, or Muromomab) (Table 12.1), it became increasingly obvious that only mAbs with a decreased immunogenicity could be used for repeated injections in Humans. The generation of a Human Anti-Mouse Antibody (HAMA) response when murine mAbs are infused to patients hampers their therapeutic efficacy and provokes side-effects related to the formation of immune-complexes. Moreover, studies developed in the 80’s indicated that the Fcγ regions of mouse IgG — the most frequent immunoglobulin isotype of mAbs — trigger effector functions in Humans with a lower efficacy than their human Fcγ counterparts. Notably, the level of Complement-Dependent Cytotoxicity (CDC) and of Antibody-Dependent Cell Cytotoxicity (ADCC) that can be achieved is lower when mouse antibodies are used in vitro with human serum or cells from human origin, respectively.Table 12.1

Table 12.1

Summary of Currently Approved and Marketed Therapeutic mAbs

Antibody

Name

Origin

Molecular target

Indication

Company §

OKT3

Orthoclone Muromomab

Mouse

CD3

Transplantation

J&J

Panorex+

Edrecolomab

Mouse

EpCAM

Oncology

Centocor, GSK

Reopro

Abciximab

Chimeric

gpllb/IIIa

CVD*

Lilly

Rituxan

Rituximab

Chimeric

CD20

Oncology

Genentech, Roche

Simulect

Basiliximab

Chimeric

CD25

Transplantation

Novartis

Remicade

Infliximab

Chimeric

TNFα

Inflammation

J&J

Zenapax

Daclizumab

Humanised

CD25

Transplantation

Roche

Synagis

Palivizumab

Humanised

RSV*

Infectious Disease

Medimmune

Herceptin

Trastuzumab

Humanised

HER2/Neu

Oncology

Genentech, Roche

Mylotarg

Gemtuzuma (Ozogamicin)

Humanised

CD33

Oncolog

AHP,Wyeth Lab., Celltech

Campath

Alemtuzumab

Humanised

CD52

Oncology

Millennium

Zevalin

Ibritumomab

9OYMouse

CD20

Oncology

IDECPharm., Schering AG

Humira

Adalimuma

Human

TNFα

RA*

CAT, BASF, AbbottLabs

Enbre

Etanercept

Human

TNFα

RA*, PA*

Amgen, Immunex

*RSV: Respiratory Syncytial Virus; CVD: CardioVascular DiseasesIRestenosis; RA: Rheumatoid Arthritis; PA: Psoriatic Arthritis

+Approved in Germany not in USA

§MarketerslCorporate sponsors

Keywords

Effector Function Therapeutic Antibody Antibody Engineering Therapeutic Monoclonal Antibody Antibody Effector Function 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2004

Authors and Affiliations

  1. 1.15 rue de l’Ecole de MédecineUnité INSERM 255, Centre de Recherches Biomédicales des Cordeliers75270 Paris cedex 06France
  2. 2.Laboratoire Français du Fractionnement et des BiotechnologiesLes UlisFrance

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