Targeting Human Endogenous Retrovirus K Envelope Protein Inhibits Breast Cancer Growth


Get Permission

The human genome contains a large variety of endogenous retroviral sequences (approximately 8% of the genome). Although most of these are highly defective, the human endogenous retrovirus type K (HERV-K) family shows conservation of apparently intact retroviral genes and is transcriptionally active in several human cancer tissues and tumor cell lines. Full-length HERV-K transcripts have been shown to be expressed in human breast cancer, and the envelope (env) protein of the HERV-K family is commonly expressed on the surface of breast cancer cells.

Novel Immunotherapy

In a recent study, Wang-Johanning and colleagues from The University of Texas MD Anderson Cancer Center, Houston, assessed the effects of targeting HERV-K env with anti-HERV-K env monoclonal antibodies in malignant breast cancer cell lines and in mice bearing xenografts tumors. In this study, the expression of HERV-K env protein in malignant breast cancer cell lines was substantially higher than that in nonmalignant breast cells.

Several anti-HERV-K-specific monoclonal antibodies inhibited growth and induced apoptosis of breast cancer cells in vitro. Mice treated with anti-HERV-K antibody had significantly reduced growth of tumors (eg, mean size 475 vs 1,448 mm3 for tumors from malignant cell line MDA-MB-231, P < .001) compared with mice receiving control immunoglobulin. Expression of a number of proteins involved in apoptosis signaling pathways was increased in vitro in malignant breast cancer cells treated with monoclonal antibodies compared with those treated with control immunoglobulin.

In a study in 223 primary human breast tumors, 148 (66%) exhibited HERV-K expression, with HERV-K–positive tumors being associated with a significantly higher rate of lymph node metastasis compared with HERV-K-negative tumors (43% vs 23%, P = .003). As stated by the investigators, these findings suggest that “monoclonal antibodies against HERV-K env protein show potential as novel immunotherapeutic agents for breast cancer therapy.” ■

Wang-Johanning F, et al: J Natl Cancer Inst 104:189-210, 2012.


Advertisement

Advertisement



;
Advertisement

By continuing to browse this site you permit us and our partners to place identification cookies on your browser and agree to our use of cookies to identify you for marketing. Read our Privacy Policy to learn more.