Active and Passive Immunotherapy for Lymphoma: Proving Principles and Improving Results

Abstract

Conventional chemotherapy for lymphoma has advanced greatly over the past 50 years, changing some lymphoma subtypes from uniformly lethal to curable; however, the majority of lymphomas in patients remain incurable, and there is a need for novel therapies with less toxicity and more specific targeting of tumor cells. The vertebrate immune system has evolved the capacity for such specific targeting through the B-cell and T-cell receptors; passive immunotherapies utilizing these receptors, such as monoclonal antibodies (mAbs) or T cells, have shown efficacy in treating lymphomas. The first generation of mAb-based therapies has transformed the standard of care for lymphoma, and newer antibodies may improve on this approach. Clinical activity has been shown by T cells bearing receptors that target viral antigens as well as T cells bearing re-engineered receptors that target antigens recognized by antibodies. Active immunotherapies, such as vaccines and immune checkpoint blockades, have prolonged survival in certain solid tumors and are being actively pursued to treat lymphoma. A variety of vaccines (eg, protein- and cell-based vaccines) are being tested in ongoing trials, and the most recent iterations show therapeutic activity. Newer trials are addressing the problem of tumor-induced immunosuppression by the use of antibodies against immunologic checkpoints or by the reinfusion of primed T cells after lymphodepletion, a process we refer to as immunotransplantation. Herein, we discuss results of the various immunotherapy strategies applied to lymphoma and the ongoing approaches for their improvement.