Tumour surface antigens

The transformation of a cell to the cancerous state is normally associated with increased surface expression of antigens recognized as foreign by the host immune system. These surface antigens, often termed tumour antigens or tumour surface antigens, are either not expressed at all by the untransformed cell or are expressed at such low levels that they fail to induce immunological tolerance. 

ProstaScint (Capromab Pentetate murine Mab directed against the tumour surface antigen PSMA)... 

Figure 10.5. Upon transformation, cancer cells often express unique surface antigens termed tumour surface antigens (TSAs). Antibodies raised against these will selectively bind the tumour cells. The antibody used may be unconjugated or conjugated to a drug, toxin or radioactive tag...

In summary, tumour surface antigen (TSA)-based complications in the context of developing antibody-based cancer therapies include ... 

Transformed cells expressing tumour-specific surface antigens that closely resemble normal surface antigens may not induce an immune response. Furthermore, some tumour antigens, although not usually expressed in adults, were expressed previously during the neonatal period (i.e. just after birth) and are thus believed by the immune cells to be self . 

Antibodies that, by binding to the cell surface antigen, mark the tumour cell for destruction. NK cells and macrophages express cell surface receptors that bind to the antibody Fc region (Box 13.2). Thus, antibody bound to tumour antigens directs these immune elements directly to tumour surface. Antibodies also activate complement, which is capable of directly lysing tumour cells. 

Figure 13.4 Binding of appropriate antibody to tumour-associated antigens marks the tumour cell for destruction. This is largely due to the presence of a domain on the antibody Fc region (see also Box 13.2), which is recognized and bound by macrophages and NK cells. Therefore, congregation of such cells on the surface of the tumour is encouraged. This greatly facilitates their cytocidal activity towards the transformed cells...

In addition to its effects on haematopoietic cells, GM-CSF can also affect the function of mature cells. GM-CSF treatment increases the survival, cytotoxicity and eicosanoid formation by eosinophils, and can increase the tu-mouricidal activity, cytokine expression, surface antigen expression and oxidative metabolism of macrophages. It is chemotactic for endothelial cells, can induce the proliferation of some tumour cells, stimulates histamine release from basophils and affects the viability and function of Langerhans cells. Its effects on mature neutrophils are described in 7.2.1, 7.3.4. 

Tissue plasminogen activator Tumour necrosis factor Monoclonal antibody preparations y-Globulin preparations Hepatitis B surface antigen... 

Humaspect (Votumumab, human Mab directed against cytokeratin tumour-associated antigen) Mabthera (Rituximab, chimaeric Mab directed against CD20 surface antigen of B lymphocytes. See also Rituxan)... 

Oehm A, Behrmann I, Kalk W, Pawlita M, Maier G, Klas C, Li-Weber M, Richards S, Dhein J, Trauth BC, Ponsting H, Krammer PH (1992) Purification and molecular cloning of the APO-1 cell surface antigen, a member of the tumour necrosis fac-tor/nerve growth factor receptor family. J Biol Chem 267 10709-10715... 

One new approach that is being developed to enhance tumour specificity used monoclonal antibodies (mAb), raised against a particular type of tumour, as a kind of molecular "guided missile", with a porphyrin attached to the mAb as the light-activated "warhead." Tumour cells have different surface antigens to normal cells, and it is possible to raise mAbs specific for these antigens. Tumour cells also differ from normal cells in that they express a large number of low-density lipoprotein receptors. Hydrophobic photosensitisers may then be incorporated into a lipid moiety of such a receptor, and taken into the tumour cell via lysosomes. 

Purification of an organ-specific tumour-associated antigen from rat mammary carcinoma Affinity chromatography of surface glycoproteins and immunoglobulin E receptors from rat basophilic leukaemia cells Affinity chromatography of membrane immunoglobulins M and D from murine lymphocytes study of their affinities for the lectin... 

Confluent monolayers of cell lines expressing cell surface antigen for example, tumour cell lines overexpressing... 

Monoclonal antibodies have now been produced against a wide range of medically important antigens such as serum proteins, enzymes, cell surface receptors, hormones, drugs, viruses and tumour-specific antigens. Their extreme specificity means that the antibody will react with only one particular target molecule such as a drug or hormone, which can then be identified in very low concentrations in the tissues. 

Antibody binding to many tumour antigens triggers the immediate loss of the antibody-antigen complex from the transformed cell surface, either by endocytosis or extracellular shedding. 

IL-2-stimulated cytotoxic T cells appear even more efficacious than LAK cells in promoting tumour regression. The approach adopted here entails removal of a tumour biopsy, followed by isolation of T-lymphocytes present within the tumour. These tumour-infiltrating lymphocytes (TILs) are cytotoxic T-lymphocytes that apparently display a cell surface receptor which specifically binds the tumour antigen in question. They are thus tumour-specific cells. Further activation of these TILs by in vitro culturing in the presence of IL-2, followed by reintroduction into the patient along with IL-2, promoted partial/full tumour regression in well over 50 per cent of treated patients. 

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