COMBODY: one-domain antibody multimer with improved avidity.
Antibodies (Abs) have been engineered into small antigen-binding fragments and rebuilt into multivalent high-avidity molecules for improving in vivo pharmacokinetics and efficacy in clinical use. To increase the avidity of a T-cell receptor-like single-domain Ab (sdAb) specific for HLA-A2 complex, we fused the sdAb to a coiled-coil peptide derived from human cartilage oligomeric matrix protein (COMP48) to make an sdAb multimer, termed combody. The combody improved the binding avidity of sdAb significantly, whereas the specificity for the targeted cells was retained. The strategy was also expanded to create a bispecific combody by fusing an sdAb to the N-terminal and an anti-CD3 single-chain variable fragment to the C-terminal of COMP48. The dual-specific combody was able to efficiently mediate cytotoxicity against the target cells in vitro. Taken together, the strategy to make combody could be widely adopted to increase the avidity of Ab fragment for further application.
Zhu
Xuekai
X
CAS Key Laboratory of Pathogenic Microbiology and Immunology (CASPMI), Institute of Microbiology, Chinese Academy of Sciences, Beijing, PR China.
Wang
Lei
L
Liu
Rongzhi
R
Flutter
Barry
B
Li
Shenghua
S
Ding
Jie
J
Tao
Hua
H
Liu
Changzhen
C
Sun
Meiyi
M
Gao
Bin
B
D018033:Antibodies, Bispecific / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000915:Antibody Affinity / Q000235:genetics* / Q000276:immunology; D001666:Binding Sites, Antibody / Q000235:genetics; D017252:CD3 Complex / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005240:Feasibility Studies; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D058965:MART-1 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D064235:Matrilin Proteins; D015202:Protein Engineering; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics
D018033:Antibodies, Bispecific; D017252:CD3 Complex; D002272:Carcinoembryonic Antigen; D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D015789:HLA-A2 Antigen; D058965:MART-1 Antigen; D064235:Matrilin Proteins; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; C577553:TSP5 protein, human