Tumor Penetrating Peptide-Functionalized Tenascin-C Antibody for Glioblastoma Targeting.

Prakash Lingasamy, Anett-Hildegard Laarmann, Tambet Teesalu

Current cancer drug targets 2021

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Conjugation to clinical-grade tumor penetrating iRGD peptide is a widely used strategy to improve tumor homing, extravasation, and penetration of cancer drugs and tumor imaging agents. The C domain of the extracellular matrix molecule Tenascin-C (TNC-C) is upregulated in solid tumors and represents an attractive target for clinical-grade single-chain antibody- based vehicles for tumor delivery drugs and imaging agents. To study the effect of C-terminal genetic fusion of the iRGD peptide to recombinant anti- TNC-C single-chain antibody clone G11 on systemic tumor homing and extravasation. Enzyme-linked immunosorbent assay was used to study the interaction of parental and iRGD-fused anti-TNC-C single-chain antibodies with C domain of tenascin-C and αVβ3 integrins. For systemic homing studies, fluorescein-labeled ScFV G11-iRGD and ScFV G11 antibodies were administered in U87-MG glioblastoma xenograft mice, and their biodistribution was studied by confocal imaging of tissue sections stained with markers of blood vessels and Tenascin C immunoreactivity. In a cell-free system, iRGD fusion to ScFV G11 conferred the antibody has a robust ability to bind αVβ3 integrins. The fluorescein labeling of ScFV G11-iRGD did not affect its target binding activity. In U87-MG mice, iRGD fusion to ScFV G11 antibodies improved their homing to tumor blood vessels, extravasation, and penetration of tumor parenchyma. The genetic fusion of iRGD tumor penetrating peptide to non-internalizing affinity targeting ligands may improve their tumor tropism and parenchymal penetration for more efficient delivery of imaging and therapeutic agents into solid tumor lesions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Citation

Prakash Lingasamy, Anett-Hildegard Laarmann, Tambet Teesalu. Tumor Penetrating Peptide-Functionalized Tenascin-C Antibody for Glioblastoma Targeting. Current cancer drug targets. 2021;21(1):70-79