Lysyl oxidase like‐4 monoclonal antibody demonstrates therapeutic effect against head and neck squamous cell carcinoma cells and xenografts

• Published in: International journal of cancer Vol. 138; no. 10; pp. 2529 - 2538
• Main Authors: Görögh, Tibor, Quabius, Elgar S., Heidebrecht, Hans, Nagy, Andreas, Muffels, Till, Haag, Jochen, Ambrosch, Petra, Hoffmann, Markus
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 15.05.2016
• Subjects: Amino Acid Oxidoreductases - antagonists & inhibitors; Amino Acid Oxidoreductases - genetics; Amino Acid Oxidoreductases - metabolism; Animals; Antibodies, Monoclonal - pharmacology; antibody therapy; Antineoplastic Agents - pharmacology; Antitumor activity; Biopsy; Biotechnology; Cancer; Cancer therapies; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell Line, Tumor; Cell Membrane - metabolism; Chemical compounds; Cross-reactivity; Cytotoxicity; Disease Models, Animal; Epithelium; Female; Gene Expression; Head & neck cancer; head and neck cancer; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Humans; Immunization; Immunodeficiency; Immunoglobulins; Immunohistochemistry; Immunotherapy; Liquid oxygen; Lysyl oxidase; Medical research; Mice; Monoclonal antibodies; Neoplasm Grading; Neoplasm Staging; Oxidase; Rodents; Severe combined immunodeficiency; Splenocytes; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck; Tumor cell lines; Tumor cells; Tumors; Xenograft Model Antitumor Assays; Xenografts; head and neck cancer; lysyl oxidase; antibody therapy
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.29986

A new member of the lysyl oxidase (LOX) family, lysyl oxidase‐like 4 (LOXL4), is overexpressed in head and neck squamous cell carcinoma (HNSCC) compared to normal squamous epithelium. A monoclonal antibody (mAb) derived from fusion of Balb/c mouse splenocytes immunized with LOXL4 specific peptide was used to evaluate its therapeutic efficacy in 15 HNSCC cell lines associated with LOXL4 overexpression. For xenograft experiments 41 severe combined immunodeficient (SCID) mice were used to analyze LOXL4‐mAb mediated tumor regression. Cell viability was analyzed using cytotoxicity‐, and clonogenic‐assays. Significant suppression of tumor cell growth was observed in 12 out of 15 (80%) tumor cell lines after 48 hr exposure to the mAb (LD50 of 15 µg/ml to 45 µg/ml). The effect induced by the antibody could be blocked by pre‐incubation of the antibody with the peptide used for immunization of the mice and antibody generation, indicating that the effect of the antibody is specific. In mice inoculated with HNSCC cells, i.v. injections of the LOXL4‐mAb resulted within 70 days in extensive tumor destruction in all treated animals whereas no tumor regression occurred in control animals. In mice pre‐immunized i.v. with LOXL4‐mAb and subsequently injected with HNSCC cells, tumor development was considerably delayed in contrast to non LOXL4‐mAb pre‐immunized animals. These results demonstrate that the LOXL4‐mAb has potent antitumor activity and suggest its suitability as a therapeutic immune agent applicable to HNSCC exhibiting tumor specific upregulation of LOXL4. What's new? A newly developed antibody shows promise against HNSCC. Previous results have shown that head and neck squamous cell carcinoma (HNSCC) tumor cells churn out an excess of the enzyme LOXL4, but so far, antibodies against LOXL4 have also shown cross‐reactivity with normal tissue. In this paper, the authors report on a new antibody they've developed against LOXL4. The antibody suppressed growth in 12 of the 15 LOXL4‐overexpressing cell lines tested. Then, they gave the antibody to mice with HNSCC tumors, and observed extensive tumor destruction in all treated animals.