Natural killer (NK) cells and anti-tumor therapeutic mAb: unexplored interactions

Abstract

Tumor-targeting mAb are widely used in the treatment of a variety of solid and hematopoietic tumors and represent the first immunotherapeutic approach successfully arrived to the clinic. Nevertheless, the role of distinct immune mechanisms in contributing to their therapeutic efficacy is not completely understood and may vary depending on tumor- or antigen/antibody-dependent characteristics. Availability of next-generation, engineered, tumor-targeting mAb, optimized in their capability to recruit selected immune effectors, re-enforces the need for a deeper understanding of the mechanisms underlying anti-tumor mAb functionality. NK cells participate with a major role to innate anti-tumor responses, by exerting cytotoxic activity and producing a vast array of cytokines. As the CD16 (low-affinity FcγRIIIA)-activating receptor is expressed on the majority of NK cells, its effector functions can be ideally recruited against therapeutic mAb-opsonized tumor cells. The exact role of NK cells in determining therapeutic efficacy of tumor-targeting mAb is still unclear and much sought after. This knowledge will be instrumental to design innovative combination schemes with newly validated immunomodulatory agents. We will summarize what is known about the role of NK cells in therapeutic anti-tumor mAb therapy, with particular emphasis on RTX chimeric anti-CD20 mAb, the first one used in clinical practice for treating B cell malignancies.

Optimization of Large-Scale Expansion and Cryopreservation of Human Natural Killer Cells for Anti-Tumor Therapy

“…The percentage of CD16 + NK cells was not changed by cryopreservation. Recently, the combination of NK cells with therapeutic antibodies was shown to suppress tumors more effectively (2425). Rituximab is the first monoclonal antibody successfully used for the treatment of patients with CD20 + lymphoma or leukemia (2627).…”

Restricted processing of CD16a/Fc γ receptor IIIa N-glycans from primary human NK cells impacts structure and function

“…The activating role of CD16a in ADCC by NK cells is well established (1). Indeed, investigations of rituximab, trastuzumab and cetuximab therapeutics demonstrated the importance of CD16a on NK cells for success (4).…”

“…ADCC is predominantly performed by natural killer (NK) cells (1), cytolytic lymphocytes present as 1-6% of circulating leukocytes (2,3) that express FcgRIIIa/CD16a as the predominant FcgR. The activating role of CD16a in ADCC by NK cells is well established (1).…”

Effect of heated naringenin on immunomodulatory properties and cellular antioxidant activity

“…Quiet NK cell activity is associated with an increase in the risk of carcinogenesis. Therefore, the focus of recent cancer treatment is to develop drugs that promote NK cells (Battella et al 2015;Vivier et al 2012). In fact, we evaluated the cytotoxic effect of NK cells on target cells by co-culturing spleens with K562 myelogenous leukemia cells as NK-sensitive cells.…”