Development of a novel small antibody that retains specificity for tumor targeting.
BACKGROUND
For the targeted therapy of solid tumor mediated by monoclonal antibody (mAb), there have different models of rebuilding small antibodies originated from native ones. Almost all natural antibody molecules have the similar structure and conformation, but those rebuilt small antibodies cannot completely keep the original traits of parental antibodies, especially the reduced specificity, which gravely influences the efficacy of small antibodies.


METHODS
In this study, authors developed a novel mimetic in the form of V(H)FR1(C-10-)V(H)CDR1-V(H)FR2-V(L)CDR3-V(L)FR4(N-10) for a parental mAb induced with human breast cancer, and the mimetic moiety was conjugated to the C-terminal of toxicin colicin Ia. The novel fusion peptide, named protomimecin (PMN), was administered to MCF-7 breast cancer cells to demonstrate its killing competency in vitro and in vivo.


RESULTS
Compared with original antibody-colicin Ia (Fab-Ia) and single-chain antibody-colicin Ia (Sc-Ia) fusion proteins, PMN retained the targeting specificity of parental antibody and could specifically kill MCF-7 cells in vitro. By injecting intraperitoneally into BALB/c athymic mice bearing MCF-7 tumors, with reduced affinity, PMN significantly suppressed the growth of tumors compared with control mice treated by toxicin protein, Fab-Ia protein, Sc-Ia protein or by PBS (p < 0.05).


CONCLUSIONS
This novel mimetic antibody retained original specificity of parental antibody, and could effectively guide killer moiety to suppress the growth of breast cancer by targeted cell death.
Zhen
Zi-Peng
ZP
Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu 610041, PR China. zhzp1120@yahoo.com.cn
Zhang
Jie
J
Zhang
Si-Yuan
SY
D000818:Animals; D000906:Antibodies / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000918:Antibody Specificity; D002460:Cell Line; D002470:Cell Survival / Q000276:immunology; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012680:Sensitivity and Specificity; D023041:Xenograft Model Antitumor Assays
D000906:Antibodies; D011993:Recombinant Fusion Proteins