Immune Dysfunction in Chronic Lymphocytic Leukemia: The Role for Immunotherapy

John      C. Riches; Alan      G. Ramsay; John      G. Gribben

Abstract

A key feature of the clinical course of chronic lymphocytic leukemia (CLL) is that it induces a state of immunosuppression, causing increased susceptibility to infections and failure of anti-tumor immune responses. Cytotoxic chemotherapy still forms the mainstay of most current treatment regimens, but is not curative, and its lack of specificity means that it also targets normal immune cells, exacerbating this immunosuppression. This can result in effective treatments being limited by infectious complications, particularly in the elderly who comprise the majority of patients with this disease. Immunotherapy potentially offers a way out of this dilemma, due to its improved specificity and ability to enhance immune responses to both the tumor and infectious agents. There has been a dramatic increase in the range of available immunotherapeutic options over the past decade, and many are now in the process of making the transition to the clinic. This review will discuss both the immune defect in CLL, and emerging immunotherapies, including CD40 ligand gene therapy, lenalidomide, CLL vaccines, CXCR4 antagonists, and adoptive cellular immunotherapies such as chimeric antigen receptor modified T-cells.

Keywords: Chronic lymphocytic leukemia, immune suppression, T-cell, NK-cell, CXCR4, plerixafor, CAL-101, everolimus, PCI-32765, CD40 ligand, gene therapy, lenalidomide, cancer vaccine, allogeneic hemopoietic stem cell transplantation, chimeric antigen receptor