Katsuji Hironaka

Adoptive Immunotherapy of Cancer Using Autologous Lymphocytes

Adoptive immunotherapy (AIT) of cancer using lymphocytes is a highly promising modality for eradicating cancer. The AIT strategy is less dependently of cancer-associated immune dysfunction, which exists in tumor-bearing host. The cloning of interleukin-2 (IL-2) has facilitated to manipulate and to propagate effector cells. Lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TILs) were introduced into clinical trials for cancer treatment and demonstrated, to some extents, objective tumor responses. Identification of tumor antigens and understanding of antigen presentation and recognition machinery has permitted to stimulate HLA-restricted antigen-specific lymphocytes with dendritic cells (DCs) and tumor antigens, including peptide, tumor lysate, tumor fusion, and tumor RNA. HLA-un-restricted effector cells, including NKT cells and γδT cells, have also been promising to investigate. It is the most important to define and establish a suitable culture system that can permit adequate expansion of effector lymphocytes with sufficient activities that can persist in vivo. It must also be of importance to conduct scientific clinical trials for establishing effective AIT applications. I believe, the time is coming soon when the AIT can provide clinical benefits for patients with advanced cancer in the world.