Abstract

The overall goal of ongoing research is the design and characterization of recombinant immunoglobulin (Ig) forms for use in both therapeutic and diagnostic applications for a range of human cancers. Emphasis is being placed on the design and translational research of humanized CDR-grafted and CDR-modified Ig forms, domain-deleted Ig forms and single-chain fusion molecules. These studies are being conducted using a monoclonal antibody (MAb) of potential clinical utility designated CC49. This MAb has been shown to target a wide range of human tumors clinically and has demonstrated anti-tumor activity in clinical trials as a murine Ig. Studies are ongoing to identify those CDRs that are essential for antigen binding and those that may be immunogenic in humans to better define those variants that are of potential clinical utility.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010429-04
Application #
6951752
Study Section
(LTIB)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2003
Total Cost
Indirect Cost

  Institution

Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Kashmiri, Syed V S; De Pascalis, Roberto; Gonzales, Noreen R et al. (2005) SDR grafting--a new approach to antibody humanization. Methods 36:25-34
Gonzales, Noreen R; De Pascalis, Roberto; Schlom, Jeffrey et al. (2005) Minimizing the immunogenicity of antibodies for clinical application. Tumour Biol 26:31-43
Milenic, Diane; Garmestani, Kayhan; Dadachova, Ekaterina et al. (2004) Radioimmunotherapy of human colon carcinoma xenografts using a 213Bi-labeled domain-deleted humanized monoclonal antibody. Cancer Biother Radiopharm 19:135-47
Gonzales, Noreen R; Padlan, Eduardo A; De Pascalis, Roberto et al. (2004) SDR grafting of a murine antibody using multiple human germline templates to minimize its immunogenicity. Mol Immunol 41:863-72
Gonzales, Noreen R; Padlan, Eduardo A; De Pascalis, Roberto et al. (2003) Minimizing immunogenicity of the SDR-grafted humanized antibody CC49 by genetic manipulation of the framework residues. Mol Immunol 40:337-49
De Pascalis, Roberto; Gonzales, Noreen R; Padlan, Eduardo A et al. (2003) In vitro affinity maturation of a specificity-determining region-grafted humanized anticarcinoma antibody: isolation and characterization of minimally immunogenic high-affinity variants. Clin Cancer Res 9:5521-31