Metastatic cancers are the cause of up to 90% of cancer deaths, yet few treatment options exist for patients with metastatic disease. Adoptive transfer of T cells that express tumor-reactive T-cell receptors (TCRs) has been shown to mediate regression of metastatic cancers in some patients. Unfortunately, identification of antigens that are expressed solely by cancer cells and not normal tissues has been a major challenge for the development of T-cell based immunotherapies. Thus, it is essential to find novel target antigens that are differentially expressed in cancer versus normal tissues.
Researchers at the National Cancer Institute’s Experimental Transplantation and Immunology Branch (NCI ETIB) have developed a TCR that specifically targets the Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1) 52-60 epitope. KK-LC-1 antigen (encoded by the CT83 gene) is highly expressed by several common and aggressive epithelial tumor types. Importantly, KK-LC-1 is expressed at very low levels in normal tissues, and is not expressed in life-essential tissues. This expression profile makes KK-LC-1 an attractive target for T-cell based anti-cancer therapies.
This TCR may be used to genetically modify peripheral blood lymphocytes from eligible patients. After expansion, these genetically modified T cells can be used to treat patients. It may also be possible to use portions of the KK-LC-1 TCR in chimeric proteins for cancer therapy and/or for antigen detection assays
- Differential expression profile of KK-LC-1 in cancers versus normal tissues suggests that therapy with a specific KK-LC-1 TCR would be cancer-specific and would not damage life-essential tissues;
- Thousands of cancer patients each year with otherwise untreatable disease may be eligible for gene therapy with this TCR
- Therapeutic use against several common and aggressive epithelial tumor types