Expansion of Mucin-Reactive T-helper Lymphocytes from Patients with Colorectal Cancer

Abstract
The ability to identify and expand effector cells with reactivity against tumor-associated antigens (TAA) is critical for effective adoptive cellular therapy. The purpose of this study was to assess lymph node lymphocytes sensitized in vivo to the shed TAA TAG-72 as a potential source of cells for adoptive cellular therapy. Lymph nodes containing microscopic tumor and/or shed TAG-72+ mucin were localized using radiolabeled CC49 monoclonal antibody and a gamma detector at the time of exploratory colorectal surgery. Lymph nodes containing microscopic tumor and shed mucin exhibited approximately 40-fold expansion in short-term (+ mucin. In addition,CD4+ cells expressed mRNA for IL-2, IL-4, tumor necrosis factor-β and IFNg, and retained the ability to secrete IL-2 after expansion. Thus, noncytolytic, cytokine-secreting, mucin-reactive T- cells can be expanded from lymph nodes of patients with colorectal cancer. These cells provide the basis for T-helper adoptive cellular therapy programs of patients with advanced colorectal cancer.