T-Cell Immunotherapy that Targets Aggressive Epithelial Tumors

Metastatic cancers cause 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 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 differentially expressed in cancer versus normal tissues.

Inventors at the National Cancer Institute (NCI) 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 not in those tissues vital for survival. 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 (T cells) 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 antigen detection assays. This technology is currently being evaluated in clinical trials at the NCI and at Rutgers Cancer Institute of New Jersey.

NCI’s Center for Immuno-Oncology seeks licensees and/or co-development partners for a T-cell immunotherapy that targets KK-LC-1 for use in the treatment of epithelial cancers.

Commercial Applications:

• Therapeutic against several common and aggressive epithelial tumor types – such as ovarian cancer

Competitive Advantages:

• Differential expression profile of KK-LC-1 suggests that therapy with a specific KK-LC-1 TCR could be cancer-specific and would not damage normal tissues
• The repertoire of targetable epithelial antigens for TCR-T cell therapy is larger than for CAR-T cells
• Increased sensitivity may improve tumor cell detection and killing versus CAR-T cells, due to lower epitope density required for activation
• Higher avidity and lower affinity could result in each TCR-T cell destroying numerous antigen-presenting cancer cells
• Thousands of cancer patients each year with otherwise untreatable disease may be eligible for immunotherapy with this TCR