Monoclonal antibodies against human oral squamous cell carcinoma reacting with keratin proteins

Myoken, Yoshinari; Moroyama, Takamasa; Miyauchi, Shunsuke; Takada, Kazuaki; Namba, Masayoshi

doi:10.1002/1097-0142(19871215)60:12<2927::aid-cncr2820601214>3.0.co;2-0

Cited by 17 publications

(4 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also developed an affinity purified polyclonal antibody raised against the 85 kD LOXL4 antigen to demonstrate its expression in HNSCC tissues of different grading and staging, and studied its involvement in the structural organisation of squamous epithelia . So far, most of the described antibodies against HNSCC showed considerable cross reactivity with normal tissue or showed only reactivity with SCC of distinct sites of origin . The first successful radioimmunotherapy results for HNSCC were shown with the E48 mAb in the early 1990 sec .…”

mentioning

confidence: 99%

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

Görögh

Quabius

Heidebrecht

et al. 2016

Intl Journal of Cancer

View full text Add to dashboard Cite

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 mg/ml to 45 mg/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.Lysyl oxidases are a family of five copper-dependent amine oxidases including LOX, LOXL, LOXL2, LOXL3 and LOXL4 that catalyze the oxidation of peptidyl lysine to d-aminoadipic b-semialdehyde, the intermediate precursor during the formation of covalent crosslinkages that stabilize fibres of elastin and collagen, and contribute to the development and maintenance of the extracellular matrix. [1][2][3] LOX is expressed in several human tumor cells such as melanoma cells, fibrosarcoma and rhabdosarcoma cells, and in prostate and breast carcinoma. 4-6 It has been found both extracellular and intracellular, 7,8 and has multiple functions in stromal and epithelial cells and tissues, for example, maturation of fibrillar matrix proteins in fibrosing processes and dictates their stability against metalloproteinases. 9-11 Studies investigating the role of LOX in invasive breast carcinoma cells revealed that LOX activity was essential in promoting the invasive phenotype of breast carcinoma cells 12,13 and the metastatic behavior in mice. 14 It was also demonstrated that hydrogen peroxide generated during LOX-catalyzed reactions mediated FAK/Scr activation, turnover of focal adhesions, and increased cell migration. 13 A recent study showed that LOXL4 is induced by transforming growth factor b1 (TGF-ß1) and plays a role in ECM remodeling. 15 We have found selective upregulation and amplification of the LOXL4 gene, overexpression of LOXL4 protein in primary and metastatic HNSCC cell ...

show abstract

mentioning

confidence: 99%

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

Görögh

Quabius

Heidebrecht

et al. 2016

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…There have been a number of successful attempts at producing MAbs to SCC tissue (Brenner et al, 1982;Carey et al, 1983;Bernal and Speak, 1984;Boeheim et al, 1985;Kyoizumi et al, 1985;Stahel et a l . , 1985;Fernstein et al, 1986;Hanai et al, 1986;Kimmel and Carey, 1986;Gioanni et al, 1987;Myoken et al, 1987;Ranken et al, 1987). That few of these Mabs have found an important role to play in immunohistochemistry reflects several shortcomings.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of monoclonal antibody 3H‐1 reactivity with squamous‐cell head‐and‐neck cancers

Kearsley

Leonard

Takahashi

et al. 1991

Intl Journal of Cancer

View full text Add to dashboard Cite

We report the reactivity of a novel murine IgM monoclonal antibody (MAb), 3H-1, in formalin-fixed tissue from a series of 44 patients with squamous-cell cancers (SCCs) of the upper aerodigestive tract. The antigen detected by 3H-1 MAb is not expressed in simple squamous epithelia and only rarely in non-squamous malignancies. The following staining patterns were found to be associated with a progressively unfavourable prognosis: membranous, diffuse cytoplasmic and focal cytoplasmic/nil staining. There were no statistically-significant associations between focal cytoplasmic/nil staining and traditionally used prognostic parameters such as tumour size, nodal involvement or pathologic grade. However, multivariate analyses demonstrated that focal or nil staining was a significant independent prognostic factor for survival (p less than 0.001) and was the only significant prognostic factor for relapse (p less than 0.001). The converse applied to tumours with predominantly membranous staining (p = 0.004). 3H-1 MAb, with the advantage of relying on the pattern rather than the intensity of staining, makes it possible to identify different cellular phenotypic sub-populations more accurately than by conventional means, and may ultimately improve our understanding of the mechanisms underlying transformation from a benign or proliferative state to a malignant one.

show abstract

“…Unfortunately, only Po43, Po66, BAM33, BAM45 and control IgG1 immunoglobulin PY could be labelled efficiently. mAbs raised against human oral carcinomas, for example, were found to be reactive with keratins [16]. The loss of Po60 immunoreactivity after radioiodination might be due to the presence of tyrosine in the antigen-binding site.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the antigen identified by Po66

Martin¹,

Pellen²,

Guitton³

et al. 1989

Cancer Immunol Immunother

View full text Add to dashboard Cite

The mouse monoclonal antibody (mAb) Po66 has been shown in previous work to be localized in nude mice xenografts of human lung tumours when injected intravenously [Dazord L et al. (1987) Cancer Immunol Immunother 24: 263-268] and to be suitable for the scintigraphic detection of lung cancers in patients [Dazord L, et al. (1987) in Klapdor (ed) New tumour markers and their monoclonal antibodies. Georg Thieme, Stuttgart, New York, pp 444-450]. The nature of the antigen recognized by Po66 has been investigated in the present work and comparisons are made with antigens recognized by other mAbs prepared in the laboratory. These mAbs were raised either against lung squamous cell carcinoma (mAbs Po43, Po60), or against a bronchio-alveolar carcinoma (mAbs BAM33, BAM45, BAM54 and BAM69). Radioiodinated purified Po66 did not compete for cell binding with any other mAb. All Po and BAM mAbs reacted with tumour cells both cultured in vitro and grown in vivo. They recognized cytoplasmic antigens as judged by immunofluorescence examination of fixed cells or by immunoperoxidase staining of cancer tissues, but could never be visualized by immunofluorescence on the surface membrane of culture cells. The mAbs of the BAM series reacted with vimentin as demonstrated by immunofluorescence staining, showing alterations in the aspect of the filaments under the effect of colchicine. Radiolabelled mAbs Po43, BAM33 and BAM45 bound to partially purified cytoplasmic cytoskeleton components. In contrast, Po66 was never seen associated with intermediary filaments. The sensitivity to enzyme digestion of the antigen associated with Po66 was studied in comparison with those associated with Po43, BAM33 and BAM45. All antigens were sensitive to protease digestion while only the Po66-identified antigen was sensitive to periodate, neuraminidase and alpha-fucosidase. Thus, mAb Po66 identified an antigen of 47 kDa (as determined before) present in the cytoplasm but not related to the cytoskeleton, not detected on the cell surface and glycoprotein in nature.

show abstract

Monoclonal antibodies against human oral squamous cell carcinoma reacting with keratin proteins

Cited by 17 publications

References 21 publications

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

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

Prognostic significance of monoclonal antibody 3H‐1 reactivity with squamous‐cell head‐and‐neck cancers

Characterization of the antigen identified by Po66

Contact Info

Product

Resources

About