Tumor Antigens

The immune system plays a role in surveillance of neoplastic cells that have escaped controls on proliferation.

Some tumors have tumor-specific antigens on their surfaces. (These antigens are also called TSA, tumor-specific transplantation antigens, TSTA, tumor rejection antigens, or TRA.)

TSA are absent on non-tumor cells, and typically appear after an infecting virus has caused the cell to express viral antigens and to escape controls (become immortal). Some TSAs are not induced by viruses, but are the idiotypes of BCR on B cell lymphomas or TCR on T cell lymphomas.

Antigen

Function of Antigen

Expressed on

Cyclin-dependent kinase 4

Cell cycle regulator

Melanoma

β-catenin

Signal transduction

Melanoma

Caspase-8

Apoptosis regulator

Squamous cell carcinoma

MAGE-1MAGE-3

Normal testicular proteins

Melanoma, breast, glioma tumors;

Tyrosinase

Melanin synthesis

Melanoma

Surface Ig idiotype

BCR

Lymphoma

Her-2/neu

Receptor tyrosine kinase

Breast and ovarian cancer

MUC-1

Underglycosylated mucin

Breast and pancreatic tumors

HPV E6 and E7

Viral gene products

Cervical carcinoma

Attempts have been made to kill tumor cells employ by linking tumor-specific antibodies to toxins, anti-tumor drugs, or very energetic radioisotopes. Problems with such therapies include the time-consuming and expensive necessity of making a unique antibody for each tumor, the lack of antibody access to the tumor center, and human-anti-mouse-antibody (HAMA) responses to xenogeneic monoclonal antibodies. Although production of human monoclonals has proved difficult, chimeric antibodies and humanized antibodies can be made that are less immunogenic. In a few patients, mAb have induced tumor remission or elimination.

Tumor Antigens Targeted by mAb

Antigen Type

Specific Antigen

Tumor Type

Differentiation

CD5 Idiotype CAMPATH-1

T cell lymphoma B cell lymphoma T and B cell lymphomas

B cell signaling

CD20

Non-Hodgkin's B cell lymphoma

Growth factor receptor

Epidermal growth factor receptor p185HER2 IL-2R

Lung, breast, head, and neck tumors Breast, ovarian tumors T and B cell tumors

Cell surface glycoprotein

CEA, mucin-1

Epithelial tumors (breast, colon, lung)

Cell surface carbohydrate

Lewisx, CA-125

Epithelial tumors Ovarian carcinoma

Stromal extracellular antigen

FAP-α Tenascin Metalloproteinases

Epithelial tumors Glioblastoma multiforme Epithelial tumors

Adapted from Janeway et al. Immunobiology (5th ed.). Garland Press, New York, 2001 and here

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