Targeting Human Endogenous Retrovirus K Envelope Protein Inhibits Breast Cancer Growth

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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.