Adoptive Immunotherapy in Renal Cell Carcinoma

Abstract

The study of cancer immunotherapy has gained increasing popularity since Dr. William Coleys’ observations in the late 19th century of patient tumor shrinkage after life-threatening bacterial infections. The idea that tumor cells, similar to invading foreign pathogens, can express abnormal antigens has formed the basis of attempts to manipulate the immune system to cause improved tumor surveillance and destruction. Over the last two decades, considerable strides have been made in the field of tumor immunology. This includes further knowledge of antigen processing and presentation via the major histocompatability complex (1, 2); understanding the interaction between T cells and antigen presenting cells (APC) via the T-cell receptor (TCR) (3), secondary signals such as costimulatory molecules, regulation of the immune response by cytokines, and most notably the characterization of a variety of genes-encoding tumor-associated antigens (TAA). For many tumor types, the DNA and amino acid sequences of TAA have been worked out including the immunodominant peptide restricted by major histocompatibility complex (MHC) rules. These relatively recent discoveries have allowed for the exploration of more targeted immunotherapies. The transfer of cells with antitumor reactivity is termed adoptive immunotherapy and shows promise in the treatment of selected malignancies. Adoptively transferred T cells have been shown to bring about regression in animal tumor models (4–6), and have been studied in human clinical trials since the 1980’s. It is now evident that the potential of adoptive therapy seen in animal models has not yet fully translated into human models. However, there are well-documented studies demonstrating durable responses in human cancers, most notably renal cell carcinoma (RCC) and melanoma. This chapter will focus on the development of adoptive immunotherapy for RCC, its shortcomings, and potential for improvement. Adoptive immunotherapy employing autolymphocyte therapy (ALT), lymphokine-activated killer cells (LAK), and tumor infiltrating lymphocytes (TIL) will be featured, as will other promising approaches.