Abstract
Simple SummaryThis review is intended to provide an overview on the history and recent advances of T cell and natural killer (NK) cell-based immunotherapy. While the thymus was discovered as the origin of T cells in the 1960s, and NK cells were first described in 1975, the clinical application of adoptive cell therapies (ACT) only began in the early 1980s with the first lymphokine activated killer (LAK) cell product for the treatment of cancer patients. Over the past decades, further immunotherapies have been developed, including ACT using cytokine-induced killer (CIK) cells, products based on the NK cell line NK-92 as well as specific T and NK cell preparations. Recent advances have successfully improved the effectiveness of T, NK, CIK or NK-92 cells towards tumor-targeting antigens generated by genetic engineering of the immune cells. Herein, we summarize the promising development of ACT over the past decades in the fight against cancer.The promising development of adoptive immunotherapy over the last four decades has revealed numerous therapeutic approaches in which dedicated immune cells are modified and administered to eliminate malignant cells. Starting in the early 1980s, lymphokine activated killer (LAK) cells were the first ex vivo generated NK cell-enriched products utilized for adoptive immunotherapy. Over the past decades, various immunotherapies have been developed, including cytokine-induced killer (CIK) cells, as a peripheral blood mononuclear cells (PBMCs)-based therapeutic product, the adoptive transfer of specific T and NK cell products, and the NK cell line NK-92. In addition to allogeneic NK cells, NK-92 cell products represent a possible “off-the-shelf” therapeutic concept. Recent approaches have successfully enhanced the specificity and cytotoxicity of T, NK, CIK or NK-92 cells towards tumor-specific or associated target antigens generated by genetic engineering of the immune cells, e.g., to express a chimeric antigen receptor (CAR). Here, we will look into the history and recent developments of T and NK cell-based immunotherapy.
Highlights
The innate immune system can overcome many obstacles on its own, the role of the adaptive immune system is crucial in the second line of defense that leads to acquired immunity
Their highly specific recognition of malignant or infected cells is based on the interaction of a compatible membrane-bound T cell receptor (TCR) with short peptide motifs related to tumor-associated antigens (TAA) or viral proteins that are presented on the major histocompatibility complex (MHC) or human leukocyte antigens (HLAs) by antigen presenting cells as well as other nucleated cells [41,42,43]
The heterogenic αβ-TCR T cell population is composed of regulatory CD4+ or CD8+ T cells (Tregs), which modulate immune responses by several mechanisms, memory T cells that ensure a fast immune reaction after repeated contact with their specific antigen as well as CD4+ T helper (TH) cells, that contribute to the immune response through additional stimulation of CD8+ cytotoxic T lymphocytes (CTLs), which exert the main cytotoxic activity to eliminate infected or malignant cells [17,42,43,50,51,52,53,54]
Summary
The Past, the Present and the Future 2.1. A Historical Review of the Development of Cell Therapeutics 2.1.1. At the beginning of the 1980s, the group of Steven Rosenberg first described a novel approach to generate another type of cytotoxic effector cells for adoptive immunotherapy: lymphokine-activated killer (LAK) cells [69,70]. In 1985, Steven Rosenberg and colleagues demonstrated the safe administration of LAK cells for patients with metastatic melanoma refractory to standard therapies in a phase I trial [76]. Due to the low inherent cytotoxic activity of LAK cells, the need for large numbers of cells and the severe side effects that can result from the administration of IL-2, the development of LAK cell-based protocols was not pursued any further, but replaced by more specific immune cell therapies [75]
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