Modulation of tumor immunity by therapeutic monoclonal antibodies

Abstract

The surveillance of tumors by the immune system of cancer patients and its impact on disease progression and patient survival have been largely documented over the last years. In parallel, the use of therapeutic monoclonal antibodies (mAbs) in oncology has gained a widespread recognition as it has made it possible to increase patient survival and to ameliorate the quality of life in a number of cancers. However, the clinical responses observed following mAb treatment remain largely heterogeneous and their duration is still highly unpredictable. Recently, the concept that the injection of therapeutic antibodies not only triggers early anti-tumor events such as receptor blockade, cytostasis, apoptosis, complement-dependent cytotoxicity and/or antibody-dependent cytotoxicity but also allows the host immune system to fight tumor cells through the development of a long-lasting adaptive immunity has emerged. In the present review, we will examine the arguments that support this concept by detailing the cellular and molecular events likely to underlie the induction of an efficient anti-tumor adaptive immune response by mAbs. We will also discuss the consequences of this induction on the way therapeutic antibodies can be used and inserted in a more global immunotherapeutic approach aiming at strengthening the adaptive anti-tumor immune response developed by cancer patients.

The Immune Microenvironment: A Major Player in Human Cancers

“…The last few years have witnessed the emergence of novel efficient immunotherapies, such as a sipuleucel-T for castration-resistant prostate cancer [155], cell therapy with engineered T cells for B cell malignancies [156], anti-tumor monoclonal antibodies [157,158,159], T-cell-engaging bispecific antibodies in non-Hodgkin lymphoma [160] and anti-checkpoint antibodies in melanoma [161,162] lung cancer or pancreatic cancer [163]. These therapies have the potential to induce long-term survival in responding patients that is usually not due to the classic rapid tumor shrinkage seen after chemotherapy [163,164,165,166].…”

Trial Watch: Monoclonal antibodies in cancer therapy

“…124,125 The cellular and molecular circuitries underlying the induction of adaptive immunity by mAbs remain poorly understood. 126 As a possibility, mAbs may enhance antigen uptake or cross-presentation by DCs, 127,128 or facilitate immunogenic cell death. 129 The precise elucidation of these aspects is eagerly awaited, as it could have profound implications for the development of novel mAbs.…”

A New Approach to Cancer Therapy: The Tumor Microenvironment as Target

“…The stimulation of natural killer cells, T cells, macrophages, or dendritic cells can be used to enhance antibody-dependent cellular cytotoxicity, phagocytosis or tumor vaccine effects [396]. Besides supporting development and strengthening of the adaptive immunity, therapeutic antibodies are able to trigger early anti-tumor events such as receptor blockade, cytostasis, apoptosis, complement-dependent cytotoxicity and/or antibody-dependent cytotoxicity [397][398][399]. Bispecific antibodies are used to mount and sustain tumor-specific cellular responses or in radioimmunotherapy to improve target binding, selectivity, and efficacy [400][401][402][403].…”