Novel human monoclonal antibodies specific to the alternatively spliced domain D of Tenascin C efficiently target tumors in vivo.
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| Abstract |
Antibody-based delivery of bioactive molecules represents a promising strategy for the improvement of cancer immunotherapy. Here, we describe the generation and characterization of R6N, a novel fully human antibody specific to the alternatively spliced domain D of Tenascin C, which is highly expressed in the stroma of primary tumors and metastasis. The R6N antibody recognized its cognate tumor-associated antigen with identical specificity in mouse and human specimens. Moreover, the antibody was able to selectively localize to solid tumors in vivo as evidenced by immunofluorescence-based biodistribution analysis. Encouraged by these results, we developed a novel fusion protein (termed mIL12-R6N) consisting of the murine interleukin 12 fused to the R6N antibody in homodimeric tandem single-chain variable fragment arrangement. mIL12-R6N exhibited potent antitumor activity in immunodeficient mice bearing SKRC52 renal cell carcinoma, as well as in immunocompetent mice bearing SMA-497 glioma. The experiments presented in this work provide a rationale for possible future applications for the R6N antibody for the treatment of cancer patients.
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| Authors | Lisa Nadal, Riccardo Corbellari, Alessandra Villa, Tobias Weiss, Michael Weller, Dario Neri, Roberto De Luca |
| Journal | mAbs (MAbs) 2020 Jan-Dec Vol. 12 Issue 1 Pg. 1836713 ISSN: 1942-0870 [Electronic] United States |
| PMID | 33136526 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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