Production of a Monoclonal Antibody (K 931) to a Squamous Cell Carcinoma Associated Antigen Identified as the 17-1A Antigen

Quak, Jasper J.; Dongen, Guus A.M.S. van; Brakkee, J. G. P.; Hayashida, Diana J. S.; Balm, Alfons J. M.; Snow, Gordon B.; Meijer, Chris J.L.M.

doi:10.1089/hyb.1990.9.377

Cited by 28 publications

(14 citation statements)

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“…18,19 A number of monoclonal antibodies capable of targeting SCC were identified. 45 The most specific antibody was developed as a clinical radioisotope carrier by converting it to a human/ mouse chimera that had a slightly lower half-life in circulation but a much higher capacity for cell lysis in a mouse xenograft tumor model. 46 Later improvements led to antibodies specific for CD44v6, a variant over-expressed in SCC.…”

Section: A Anti-cd44 Antibody Conjugatesmentioning

confidence: 99%

Anticancer Therapeutics: Targeting Macromolecules and Nanocarriers to Hyaluronan or CD44, a Hyaluronan Receptor

2008

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The complex system involved in the synthesis, degradation, and binding of the high molecular weight glycosaminoglycan hyaluronic acid (hyaluronan or HA) provides a variety of structures that can be exploited for targeted cancer therapy. In many cancers of epithelial origin there is an up-regulation of CD44, a receptor that binds HA. In other cancers, HA in the tumor matrix is over-expressed. Both CD44 on cancer cells and HA in the matrix have been targets for anti-cancer therapy. Even though CD44 is expressed in normal epithelial cells and HA is part of the matrix of normal tissues, selective targeting to cancer is possible. This is because macromolecular carriers predominantly extravasate into the tumor and not normal tissue; thus CD44-HA targeted carriers administered intravenously localize preferentially into tumors. Anti-CD44 antibodies have been used in patients to deliver radioisotopes or mertansine for treatment of CD44 expressing tumors. In early phase clinical trials, patients with breast or head and neck tumors treated with anti-CD44 conjugates experienced stabilized disease. A dose-limiting toxicity was associated with distribution of the antibody-drug conjugate to the skin, a site in the body with a high level of CD44. HA has been used as a drug carrier and a ligand on liposomes or nanoparticles to target drugs to CD44 over-expressing cells. Drugs can be attached to HA via the carboxylate on the glucuronic acid residue, the hydroxyl on the Nacetylglucosamine, or the reducing end which are located on a repeating disaccharide. Drugs delivered in HA-modified liposomes exhibited excellent anti-tumor activity both in vitro and in murine tumor models. The HA matrix is also a potential target for anti-cancer therapies. By manipulating the interaction of HA with cell surface receptors, either by degrading it with hyaluronidase or by interfering with CD44-HA interactions using soluble CD44 proteins, tumor progression was blocked. Finally, cytotoxic drugs or pro-drug converting enzymes can be attached to the HA matrix to generate a cytotoxic fence around the tumor. This review describes how the complex interplay among cancer biology, the CD44-HA interaction, drug carriers and drug targeting has been used to improve anti-cancer therapies. As these approaches evolve, they hold forth the prospect of significantly improved targeted anti-cancer treatments. KeywordsAntibody; Biodistribution; Cancer; Chemotherapy; Drug-conjugate; EPR effect; Liposome; Polymer; Prodrug; Recombinant Protein The Biology of the CD44-Hyaluronan InteractionHyaluronan (HA) (Figure 1) is a high molecular weight glycosaminoglycan, extracellular matrix component essential for proper cell growth, organ structural stability, and tissue organization. The amount of HA in a tissue depends upon on a complex interplay among HA synthesis by HA synthases, 1 HA internalization by cell surface receptors, 2 Interference with the CD44-HA interaction by either targeting drugs to CD44, 14 targeting drugs to the HA matrix 15 or interfering with HA ma...

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Section: A Anti-cd44 Antibody Conjugatesmentioning

confidence: 99%

Anticancer Therapeutics: Targeting Macromolecules and Nanocarriers to Hyaluronan or CD44, a Hyaluronan Receptor

2008

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“…Epithelial cell adhesion molecule was then found to be expressed at a high level and frequency not only on colon cancer tissues but on most human adenocarcinomas as well as on squamous cell carcinomas (Quak et al, 1990). In the case of breast and ovarian cancers, Ep-CAM mRNA was found to be more than 100-fold overexpressed relative to normal epithelial tissues (Kim et al, 2003;Osta et al, 2004).…”

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Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers

et al. 2006

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Epithelial cell adhesion molecule (Ep-CAM; CD326) is used as a target by many immunotherapeutic approaches, but little data are available about Ep-CAM expression in major human malignancies with respect to level, frequency, tumour stage, grade, histologic tumour type and impact on survival. We analysed by immunohistochemical staining tissue microarrays with 4046 primary human carcinoma samples from colon, stomach, prostate and lung cancers for both frequency and intensity of Ep-CAM expression under highly standardised conditions. A total of 3360 samples were analysable. High-level Ep-CAM expression was observed in 97.7% (n ¼ 1186) of colon, 90.7% of gastric (n ¼ 473), and 87.2% of prostate cancers (n ¼ 414), and in 63.9% of lung cancers (n ¼ 1287). No detectable Ep-CAM staining was found with only 0.4% of colon, 2.5% of gastric, 1.9% of prostate cancers, and 13.5% of lung cancers. The only significant correlation of Ep-CAM expression with tumour grading was observed in colon cancer where high-level Ep-CAM expression on grade 3 tumours was down to 92.1% (Po0.0001). Adenosquamous and squamous carcinomas of the lung had a lower percentage of high-level Ep-CAM expression compared to adenocarcinomas with 35.4 and 53.6%, respectively, and with 45.5 and 17.3% of tumours being Ep-CAM negative. With the exception of moderately differentiated colon carcinoma, where patients not expressing Ep-CAM on their tumours showed an inferior survival (P ¼ 0.0014), correlation of Ep-CAM expression with survival did not reach statistical significance for any of the other cancer indications and subgroups. In conclusion, the data strongly support the notion that Ep-CAM is a prime target for immunotherapies in major human malignancies. This is because the most common human cancers show (i) a low frequency of Ep-CAM-negative tumours, (ii) a high frequency of Ep-CAM expression on cells of a given tumour, and (iii) for most cancers, an insignificant influence of tumour staging, grading and histology on Ep-CAM expression.

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“…This is especially evident for squamous epithelia, which are Ep-CAM negative, and where Ep-CAM expression is related to early preneoplastic or dysplastic changes and carcinogenesis (14,24,35,47). However, it is also true for other types of epithelium, such as transitional epithelium (urothelium), where the level of Ep-CAM expression correlates to the tumor grade (52), or simple epithelia, such as mammary gland, where enhanced levels of Ep-CAM in carcinomas are associated with a bad prognosis (46).…”

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confidence: 99%

Cytoplasmic Tail Regulates the Intercellular Adhesion Function of the Epithelial Cell Adhesion Molecule

Balzar

Bakker

Briaire-de-Bruijn

et al. 1998

Molecular and Cellular Biology

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Production of a Monoclonal Antibody (K 931) to a Squamous Cell Carcinoma Associated Antigen Identified as the 17-1A Antigen

Cited by 28 publications

References 6 publications

Anticancer Therapeutics: Targeting Macromolecules and Nanocarriers to Hyaluronan or CD44, a Hyaluronan Receptor

Anticancer Therapeutics: Targeting Macromolecules and Nanocarriers to Hyaluronan or CD44, a Hyaluronan Receptor

Frequent high-level expression of the immunotherapeutic target Ep-CAM in colon, stomach, prostate and lung cancers

Cytoplasmic Tail Regulates the Intercellular Adhesion Function of the Epithelial Cell Adhesion Molecule

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