Impact of Depleting Therapeutic Monoclonal Antibodies on the Host Adaptive Immunity: A Bonus or a Malus?

Abstract

Clinical responses to anti-tumor monoclonal antibody (mAb) treatment have been regarded for many years only as a consequence of the ability of mAbs to destroy tumor cells by innate immune effector mechanisms. More recently, it has also been shown that anti-tumor antibodies can induce a long-lasting anti-tumor adaptive immunity, likely responsible for durable clinical responses, a phenomenon that has been termed the vaccinal effect of antibodies. However, some of these anti-tumor antibodies are directed against molecules expressed both by tumor cells and normal immune cells, in particular lymphocytes, and, hence, can also strongly affect the host adaptive immunity. In addition to a delayed recovery of target cells, lymphocyte depleting-mAb treatments can have dramatic consequences on the adaptive immune cell network, its rebound, and its functional capacities. Thus, in this review, we will not only discuss the mAb-induced vaccinal effect that has emerged from experimental preclinical studies and clinical trials but also the multifaceted impact of lymphocytes-depleting therapeutic antibodies on the host adaptive immunity. We will also discuss some of the molecular and cellular mechanisms of action whereby therapeutic mAbs induce a long-term protective anti-tumor effect and the relationship between the mAb-induced vaccinal effect and the immune response against self-antigens.

Recovery of central memory and naive peripheral T cells in Follicular Lymphoma patients receiving rituximab-chemotherapy based regimen

“…Thus, we have performed a longitudinal prospective study on peripheral blood from a small-sized cohort of similarly treated FL patients with high tumor burden, each receiving the same R-CHOP induction treatment followed by a maintenance treatment for most patients (25/33). Our study focused on the analysis of T-cell compartments, as preclinical data in mouse models as well as clinical investigations have suggested that T cells may play a major role in the control of tumor progression and in responses to antibody-based treatments 37 .…”

Therapy resistance mediated by exosomes

“…It is believed that this effect is caused by the induction of an adaptive immune memory response via T- and B-lymphocytes (Fig. 3) [64]. Exosomes may interfere with this therapeutic adaptive immune response by affecting T- and B- lymphocyte function as well as antigen presentation [65].…”

Multi-parametric single cell evaluation defines distinct drug responses in healthy hematologic cells that are retained in corresponding malignant cell types

“…Cancer immunotherapies and drugs modulating the immune system are emerging as important treatment modalities for hematological and solid tumors 46,47 Monocytes and T cell subsets formed two separate clusters. B and NK cells had similar drug response patterns.…”