Reshaping human antibodies for therapy

Riechmann, Lutz; Clark, Mike; Waldmann, Herman; Winter, Greg

doi:10.1038/332323a0

Cited by 1,456 publications

(616 citation statements)

References 34 publications

Supporting

Mentioning

590

Contrasting

Unclassified

Order By: Relevance

“…It might be argued on theoretical grounds that full humanization of antibodies, using just the complementarity-determining regions (CDR) of the rodent antibody, is desirable [27]. Whilst it is true that approximately 30% of a chimeric antibody is derived directly from the rodent antibody, compared to an estimated 5% for a humanized antibody, this 30% representing the variable regions may be highly homologous to human variable regions [19].…”

Section: Discussionmentioning

confidence: 99%

Function-blocking antibodies to human vascular adhesion protein-1: A potential anti-inflammatory therapy

et al. 2005

View full text Add to dashboard Cite

Human vascular adhesion protein-1 (VAP-1) is a homodimeric 170-kDa sialoglycoprotein that is expressed on the surface of endothelial cells and functions as a semicarbazidesensitiveamineoxidase and as an adhesion molecule. Blockade of VAP-1has been shown to reduce leukocyte adhesion and transmigration in in vivo and in vitro models, suggesting that VAP-1 is a potential target for anti-inflammatory therapy. In this study we have constructed mouse-human chimeric antibodies by genetic engineering in order to circumvent the potential problems involved in using murine antibodies in man. Our chimeric anti-VAP-1 antibodies, which were designed to lack Fc-dependent effector functions, bound specifically to cell surface-expressed recombinant human VAP-1 and recognized VAP-1 in different cell types in tonsil. Furthermore, the chimeric antibodies prevented leukocyte adhesion and transmigration in vitro and in vivo. Hence, these chimeric antibodies have the potential to be used as a new anti-inflammatory therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Function-blocking antibodies to human vascular adhesion protein-1: A potential anti-inflammatory therapy

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Some humanized monoclonal antibodies have been conjugated with drugs and are undergoing clinical trials (66,(119)(120)(121). It is now possible to transplant the complimentarydetermining regions (CDRs) from a murine antibody into a human framework (122). CAMPATH-1, a CDR graft of anti-lymphoma monoclonal antibody has been very successful in the therapy of non-Hodgkin's lymphoma and rheumatoid arthritis (123)(124)(125).…”

Section: Second Generation Antibodiesmentioning

confidence: 99%

Monoclonal antibodies in drug targeting

Panchagnula

Dey

1997

Journal of Clinical Pharmacy and Therapeutics

View full text Add to dashboard Cite

SUMMARYThe objective of drug targeting is to deliver drugs to a specific site of action through a carrier system. In cancer chemotherapy, cytotoxic drugs kill cancerous cells but also damage normal cells. Monoclonal antibodies generated against specific antigens, when conjugated to cytotoxic drugs, can selectively deliver drugs to cancer cells while minimizing damage to normal cells. Of all the carrier systems available, monoclonal antibodies are gaining importance because of their high specificity. The purpose of this review is to provide a comprehensive account of the use of monoclonal antibodies in drug targeting, highlighting their scope and limitations.

show abstract

“…Compared with other human Ig subclasses, the greatest effectiveness with respect to physiological effector functions has been described for the IgGl isotype (Brtiggemann et al, 1987;Riechmann et al, 1988). We therefore selected the human IgG 1 isotype for chimerization of the anti-CD4 mAbs.…”

Section: (C) Complement Activationmentioning

confidence: 99%

Combinatorial functions of two chimeric antibodies directed to human CD4 and one directed to the α-chain of the human interleukin-2 receptor

Weissenhorn

Scheuer

Kaluza

et al. 1992

Gene

View full text Add to dashboard Cite

SUMMARYThe general feasibility of chimerization of monoclonal antibodies (mAbs) has already been shown for a large number of them. In order to evaluate in vitro parameters relevant to immunosuppressive therapy, we have chimerized and synthesized two anti-CD4 mAbs recognizing two different epitopes on the human T-lymphocyte antigen, CD4. The chimerized mAbs are produced at levels corresponding to those of the original hybridoma cell lines. With respect to activation of human complement, the individual Abs are negative; however, when used in combination, complement activation was performed. When applied in combination, they were found to modulate the CD4 antigen, whereas the individual mAb do not display this property. Individually they mediate an up to 60% inhibition of the mixed lymphocyte reaction (MLR). However, by combination of an anti-CD4 mAb with one directed against the a-chain of the human IL2 receptor, nearly 100% inhibition of the MLR was achieved, even with reduced dosage of the mAbs. Our data suggest that the combination of an anti-CD4 mAb and an anti-IL2Rcc chain mAb is more effective with respect to immunosuppression than each mAb by itself, indicating that this mAb cocktail could be a new strategy for immunosuppressive therapy.

show abstract

Reshaping human antibodies for therapy

Cited by 1,456 publications

References 34 publications

Function-blocking antibodies to human vascular adhesion protein-1: A potential anti-inflammatory therapy

Function-blocking antibodies to human vascular adhesion protein-1: A potential anti-inflammatory therapy

Monoclonal antibodies in drug targeting

Combinatorial functions of two chimeric antibodies directed to human CD4 and one directed to the α-chain of the human interleukin-2 receptor

Contact Info

Product

Resources

About