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.


Function of Antigen

Expressed on

Cyclin-dependent kinase 4

Cell cycle regulator



Signal transduction



Apoptosis regulator

Squamous cell carcinoma


Normal testicular proteins

Melanoma, breast, glioma tumors;


Melanin synthesis


Surface Ig idiotype




Receptor tyrosine kinase

Breast and ovarian cancer


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


CD5 Idiotype CAMPATH-1

T cell lymphoma B cell lymphoma T and B cell lymphomas

B cell signaling


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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Malignant Transformation

Carcinogenesis: transformation into cancer



mutagenic carcinogens

tobacco smoke


cancers of head and neck, lung, bladder

malignant mesothelioma

non-mutagenic carcinogens



increase rate of mitosis, thus increasing the opportunity for malignant mutations
radiation ionizing radiation free radicals, DNA damage

DNA viruses

RNA retroviruses

HPV, adenovirus


genetic predisposition Philadelphia chromosome chromosomal translocation

Oncogenes Proto-oncogenes

Proto-oncogenes normally function in controlling cellular growth. Proto-oncogenes are typically associated with cellular signal transduction and control of gene transcription. Oncogenes are tumor-causing, malignantly transformed (mutated) proto-oncogenes.

Growth Factor genes

Proto-oncogene/Oncogene type

Normal/Abnormal function

c-SisPDGF β-chain
v-sis gene (first oncogene with identified homology to known cellular gene) oncogene in simian sarcoma virus
int-2 gene (integration of mouse mammary tumor virus) FGF-related growth factor
KGF (Hst) gene

FGF-related growth factor

oncogene in gastric carcinoma and Kaposi's sarcoma

Receptor Tyrosine Kinases ( RTKs)

c-Fms (“fims”) gene

colony stimulating factor-1 (CSF-1) receptor

retroviral oncogene

Flg (“flag”) gene (homology to the Fms gene, so 'fms-like gene') FGF receptor
Neu (“new”) gene – conversion of proto-oncogenic to oncogenic Neu requires only a single amino acid change in the transmembrane domain EGF receptor-related gene in an ethylnitrosourea-induced neuroblastoma
Trk (“track”) genes – TrkA, TrkB and TrkC

NGF receptor-like proteins

oncogene in pancreatic cancer

Met gene hepatocyte growth factor(HGF)/scatter factor (SF) receptor
c-Kit gene mast cell growth factor receptor

Membrane Associated Non-Receptor Tyrosine Kinases (PTKs)

v-src gene first identified oncogene
c-Src gene archetypal protein tyrosine kinase
Lck gene T cell tumor line (LYSTRA cell kinase), associated with the CD4 and CD8 antigens of T cells

G-Protein Coupled Receptors (GPCRs)

Mas gene

angiotensin receptor

oncogene in a mammary carcinoma

Membrane Associated G-Proteins

three different homologs of the c-Ras gene most frequent oncogene in colorectal carcinomas

Serine/Threonine Kinases

Raf gene signaling pathway of most RTKs, very likely threonine phosphorylation of MAP kinase following receptor activation

Nuclear DNA-Binding/Transcription Factors

Myc gene (disruption by retroviral integration and transduction and chromosomal rearrangements) avian myelocytomatosis virus, human hematopoietic neoplasias
Fos gene feline osteosarcoma virus, interacts with a second proto-oncogenic protein, Jun to form a transcriptional regulatory complex (AP1)
p53 gene (single most identified mutant protein in human tumors – originally identified as a major nuclear antigen in transformed cells) Mutant forms of the p53 protein interfere with cell growth suppressor effects of wild-type p53 indicating that the p53 gene product is actually a tumor suppressor.
adapted from here.

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. . . since 10/06/06