Tumor cells surface

NHS-LC-biotin can be used to add a biotin tag to monoclonal antibodies directed at certain tumor antigens. The biotinylated monoclonals are allowed to bind to the tumor cell surfaces in vivo, and subsequent administration of an avidin or streptavidin conjugate can form the basis for inducing cytotoxic effects or creating traceable complexes for use in imaging techniques (Hnatowich et al., 1987). 

Abundant epidemiological data indicate that tumors that overexpress EGFR and/or HER-2 exhibit a worse outcome than tumors that do not overexpress these receptors. In addition, inhibition of these receptors with monoclonal antibodies has been shown to reverse transformation in preclinical models. Moreover, the measurable overexpression of EGFR and HER-2 in tumor diagnostic tissue and the lack of an obvious role for these tyrosine kinases in normal host tissues, all together, support the notion that these tumor cell surface molecules provide a therapeutic window that can be exploited in the treatment of carcinomas that overexpress EGFR and/or HER-2. 

Roe, R., Robins, R. A., Laxton, R R., and Baldwin, R W (1985) Kinetics of divalent monoclonal antibody binding to tumor cell surface antigens using flow cytometry—standardization and mathematical analysis Mol Immunol. 22, 11—21... 

There is an increased blood flow in brain tumors (ref. 589), and the blood-brain barrier is leaky in and around 9L tumors because the blood vessels associated with these (ref. 568), and other (ref. 565-567), tumors are fenestrated. This well-known leakiness of tumor capillaries, which in the case of brain tumors includes breaches in the blood-brain barrier (ref. 566,568 cf. Section 12.2), would allow extravasation of small particulate matter (cf. ref. 590-594) or LCM. Once in the tumor area, LCM remain there because of an affinity for tumor cell surface components (cf. ref. 531 see also Chapter 14). At least 4 different types of experimental tumors in rats (C6 glioma, 9L gliosarcoma, Novikoff hepatoma, and Walker-256 carcinosarcoma), as well as several spontaneous tumors in dogs (ref. 570), do interact with LCM in a preferential manner (cf. Chapters 12 and 13), suggesting that LCM affinity may be for tumor cells in general (ref. 531). 

Finally, an interesting example has been reported in the syntheses of new photoreactive neoglycolipid probes carrying carbohydrate determinants specific for some murine mammary adenocarcinoma cells for the study of lectin receptors on tumor cell surfaces.71... 

Pereira S, Maruyama H, Siegel D, Van Belle P, Elder D, Curtis P, Herlyn D, A model system for detection and isolation of a tumor cell surface antigen using antibody phage display, J. Immunol. Meth., 203(l) ll-24, 1997. 

Nicolson, G.L., Blaustein, J. (1972). The interaction of Ricinus communis agglutinin with normal and tumor cell surfaces. Biochim. Biophys. Acta. 266 543-7. 

Dennis, J. W. and Lafert6, S. (1987). Tumor cell surface carbohydrate and the metastatic phenotype. Cancer Metastasis Rev. 5, 185-204. 

An alternative strategy for chemotherapy is the use of monoclonal antibodies as carriers for enzymes to tumor cell surfaces. The enzymes convert relatively nontoxic drug precursors (prodrugs) into active anticancer drugs. ... 

Carbohydrate-related tumor markers either are (1) antigens on the tumor cell surface or (2) secreted by the tumor cells. Monoclonal antibodies have been developed against these antigens. These markers have been found to be clinically useful as tumor markers and tend to be more specific than naturally secreted markers, such as enzymes and hormones. Biochemically, they are high molecular weight mucins (Table 23-10) or blood group antigens (Table 23-11). 

The observation of unusual carbohydrate antigens led to the synthesis of glycoconju-gates that mimic unusual carbohydrate structural antigens on tumor cell surface. Synthetic... 

It is thought that tumor-associated glycoproteins are often presented in clustered form. That is, an antigenic carbohydrate appendage is attached to a serine or threonine, and the resulting carbohydrate-amino acid motif is repeated in a series of residues. To more closely approximate a tumor cell surface, a carbohydrate construct was synthesized that presents Lewis y on three consecutive amino acids. 

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