Limits...
AFM13: a first-in-class tetravalent bispecific anti-CD30/CD16A antibody for NK cell-mediated immunotherapy.

Wu J, Fu J, Zhang M, Liu D - J Hematol Oncol (2015)

Bottom Line: Monoclonal antibodies against CD20 molecule have been leading the revolution of lymphoma treatment.In addition to monoclonal antibodies against CD20 and CD30, novel agents of immunotherapeutics in clinical development are being developed and are rapidly migrating to clinical application.One area of active development is NK cell activators, such as AFM13.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

ABSTRACT
Monoclonal antibodies against CD20 molecule have been leading the revolution of lymphoma treatment. In addition to monoclonal antibodies against CD20 and CD30, novel agents of immunotherapeutics in clinical development are being developed and are rapidly migrating to clinical application. One area of active development is NK cell activators, such as AFM13. This review will highlight the latest development of AFM13 as the first-in-class tetravalent bispecific anti-CD30/CD16A antibody for NK cell-mediated immunotherapy.

No MeSH data available.


Related in: MedlinePlus

Gene structure of tetravalent bispecific AFM13 antibody domains. The heavy and light chain DNA sequences of CD30 and CD16A were molecularly engineered in the special order as shown. This figure was modified from Rothe et al. and Reusch et al. [22,27]
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4522136&req=5

Fig1: Gene structure of tetravalent bispecific AFM13 antibody domains. The heavy and light chain DNA sequences of CD30 and CD16A were molecularly engineered in the special order as shown. This figure was modified from Rothe et al. and Reusch et al. [22,27]

Mentions: AFM13 is a tetravalent bsAb against CD30 and CD16A produced from the mammalian CHO cells by Reusch et al. [27]. Initially, a human anti-CD16A antibody with no binding to 16B isoform was isolated. The variable anti-CD16A-specific human scFv was then derived. The anti-CD30 Fv domain was derived from the murine HRS-3 IgG. The heavy and light chain DNA sequences of CD30 and CD16A were then molecularly engineered in a special order (Fig. 1) [27]. The CD30 and CD16A peptide domains were linked by a 9-amino acid linker peptide to form a bispecific diabody [28]. A tandem diabody with four domains was engineered to form a single polypeptide (nonfunctional monomer) (Fig. 2). A fully functional tetravalent bispecific chimeric antibody construct (TandAb) is formed by homodimerization of the single polypeptide monomer through non-covalent interactions of the domains in the Ig heavy (VH) and light (VL) variable chains. The TandAb has a molecular weight of 104 kDa. One arm of AFM13 binds to the CD30 antigen on lymphoma cells, whereas the other arm binds to the CD16A antigen on the NK cells (Fig. 3). The anti-CD30/CD16A tetravalent bsAb AFM13 was shown to have an IC50 value of 35.8 nM for CD30 antigen. Cytotoxicity assays showed that the AFM13-mediated activation of NK cells was strictly CD30-dependent. In the absence of CD30 target cells, neither cytotoxicity nor NK cell activation was elicited by the TandAb [27].Fig. 1


AFM13: a first-in-class tetravalent bispecific anti-CD30/CD16A antibody for NK cell-mediated immunotherapy.

Wu J, Fu J, Zhang M, Liu D - J Hematol Oncol (2015)

Gene structure of tetravalent bispecific AFM13 antibody domains. The heavy and light chain DNA sequences of CD30 and CD16A were molecularly engineered in the special order as shown. This figure was modified from Rothe et al. and Reusch et al. [22,27]
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4522136&req=5

Fig1: Gene structure of tetravalent bispecific AFM13 antibody domains. The heavy and light chain DNA sequences of CD30 and CD16A were molecularly engineered in the special order as shown. This figure was modified from Rothe et al. and Reusch et al. [22,27]
Mentions: AFM13 is a tetravalent bsAb against CD30 and CD16A produced from the mammalian CHO cells by Reusch et al. [27]. Initially, a human anti-CD16A antibody with no binding to 16B isoform was isolated. The variable anti-CD16A-specific human scFv was then derived. The anti-CD30 Fv domain was derived from the murine HRS-3 IgG. The heavy and light chain DNA sequences of CD30 and CD16A were then molecularly engineered in a special order (Fig. 1) [27]. The CD30 and CD16A peptide domains were linked by a 9-amino acid linker peptide to form a bispecific diabody [28]. A tandem diabody with four domains was engineered to form a single polypeptide (nonfunctional monomer) (Fig. 2). A fully functional tetravalent bispecific chimeric antibody construct (TandAb) is formed by homodimerization of the single polypeptide monomer through non-covalent interactions of the domains in the Ig heavy (VH) and light (VL) variable chains. The TandAb has a molecular weight of 104 kDa. One arm of AFM13 binds to the CD30 antigen on lymphoma cells, whereas the other arm binds to the CD16A antigen on the NK cells (Fig. 3). The anti-CD30/CD16A tetravalent bsAb AFM13 was shown to have an IC50 value of 35.8 nM for CD30 antigen. Cytotoxicity assays showed that the AFM13-mediated activation of NK cells was strictly CD30-dependent. In the absence of CD30 target cells, neither cytotoxicity nor NK cell activation was elicited by the TandAb [27].Fig. 1

Bottom Line: Monoclonal antibodies against CD20 molecule have been leading the revolution of lymphoma treatment.In addition to monoclonal antibodies against CD20 and CD30, novel agents of immunotherapeutics in clinical development are being developed and are rapidly migrating to clinical application.One area of active development is NK cell activators, such as AFM13.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

ABSTRACT
Monoclonal antibodies against CD20 molecule have been leading the revolution of lymphoma treatment. In addition to monoclonal antibodies against CD20 and CD30, novel agents of immunotherapeutics in clinical development are being developed and are rapidly migrating to clinical application. One area of active development is NK cell activators, such as AFM13. This review will highlight the latest development of AFM13 as the first-in-class tetravalent bispecific anti-CD30/CD16A antibody for NK cell-mediated immunotherapy.

No MeSH data available.


Related in: MedlinePlus