Genetically engineered deglycosylation of the variable domain increases the affinity of an anti-CD33 monoclonal antibody Journal Article
| Authors: | Co, M. S.; Scheinberg, D. A.; Avdalovic, N. M.; McGraw, K.; Vasquez, M.; Caron, P. C.; Queen, C. |
| Article Title: | Genetically engineered deglycosylation of the variable domain increases the affinity of an anti-CD33 monoclonal antibody |
| Abstract: | M195 is a murine monoclonal antibody that binds to the CD33 antigen and is being tested for the treatment of myeloid leukemia. Surprisingly, a complementarity determining region (CDR)-grafted, humanized M195 antibody displayed a several-fold higher binding affinity for the CD33 antigen than the original murine antibody. Here we show that the increase in binding affinity resulted from eliminating an N-linked glycosylation site at residue 73 in the heavy chain variable region in the course of humanization. Re-introducing the glycosylation site in the humanized antibody reduces its binding affinity to that of the murine antibody, while removing the glycosylation site from the murine M195 variable domain increases its affinity. The removal of variable region carbohydrates may provide a method for increasing the affinity of certain monoclonal antibodies with diagnostic and therapeutic potential. © 1993. |
| Keywords: | human cell; nonhuman; animal cell; mouse; cancer immunotherapy; structure-activity relationship; animalia; monoclonal antibody; membrane antigen; antibodies, monoclonal; immunoglobulin variable region; amino acid sequence; molecular sequence data; genetic engineering; glycosylation; murinae; models, molecular; protein structure, tertiary; antigens, cd; glycoproteins; carbohydrate; antibody affinity; cd33 antigen; antigens, differentiation, myelomonocytic; binding sites, antibody; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; deglycosylation; chimeric proteins |
| Journal Title: | Molecular Immunology |
| Volume: | 30 |
| Issue: | 15 |
| ISSN: | 0161-5890 |
| Publisher: | Pergamon-Elsevier Science Ltd |
| Date Published: | 1993-10-01 |
| Start Page: | 1361 |
| End Page: | 1367 |
| Language: | English |
| DOI: | 10.1016/0161-5890(93)90097-u |
| PUBMED: | 8232322 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2019 -- Source: Scopus |
