A novel fusion protein of IP10-scFv retains antibody specificity and chemokine function.
We combined the specificity of tumor-specific antibody with the chemokine function of interferon-gamma inducible protein 10 (IP-10) to recruit immune effector cells in the vicinity of tumor cells. A novel fusion protein of IP10-scFv was constructed by fusing mouse IP-10 to V(H) region of single-chain Fv fragment (scFv) against acidic isoferritin (AIF), and expressed in NS0 murine myeloma cells. The IP10-scFv fusion protein was shown to maintain the specificity of the antiAIF scFv with similar affinity constant, and bind to the human hepatocarcinoma SMMC 7721 cells secreting AIF as well as the activated mouse T lymphocytes expressing CXCR3 receptor. Furthermore, the IP10-scFv protein either in solution or bound on the surface of SMMC 7721 cells induced significant chemotaxis of mouse T cells in vitro. The results indicate that the IP10-scFv fusion protein possesses both bioactivities of the tumor-specific antibody and IP-10 chemokine, suggesting its possibility to induce an enhanced immune response against the residual tumor cells in vivo.
Guo
Jun-Qing
JQ
Institute of Preventive Veterinary Medicine, Zhejiang University, Hangzhou 310029, PR China.
Chen
Liu
L
Ai
Hong-Wu
HW
Jing
Jian-Nian
JN
Zhou
Ji-Yong
JY
Zhang
Chu-Yu
CY
You
Shang-You
SY
D000818:Animals; D000918:Antibody Specificity; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D005822:Genetic Vectors; D007128:Immunoglobulin Fragments / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes
D017931:DNA Primers; C104577:IP10-Mig receptor; D007128:Immunoglobulin Fragments; D018121:Receptors, Cytokine; D011993:Recombinant Fusion Proteins