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

Malignant Transformation

Carcinogenesis: transformation into cancer
Type	Agent	Comment
mutagenic carcinogens	tobacco smoke asbestos	cancers of head and neck, lung, bladder malignant mesothelioma
non-mutagenic carcinogens	Estrogens Alcohol	increase rate of mitosis, thus increasing the opportunity for malignant mutations
radiation	ionizing radiation	free radicals, DNA damage
virus	DNA viruses RNA retroviruses	HPV, adenovirus HIV, HTLV
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-Sis	PDGF 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.