Tumor antigen-targeting monoclonal antibody-based immunotherapy: Orchestrating combined strategies for the development of long-term antitumor immunity.
Tumor antigen (TA)-targeting monoclonal antibody (mAb)-based treatments are considered to be one of the most successful strategies in cancer therapy. Besides targeting TAs and inducing tumor cell death, such antibodies interact with immune cells through Fc-dependent mechanisms to induce adaptive memory immune responses. However, multiple inhibitory/immunosuppressive pathways can be induced by tumor cells to limit the establishment of an efficient antitumor response and consequently a sustained clinical response to TA-targeting mAbs. Here, we provide an overview on how TA-targeting mAbs in combination with conventional cancer therapies and/or inhibitors of key immunosuppressive pathways might represent promising approaches to achieve long-term tumor control.
Institut de Recherche en Cancérologie de Montpellier; Inserm U896 ; Institut Régional de Lutte contre le Cancer (ICM); Université Montpellier 1 ; Montpellier Cedex, France.
Henri-Alexandre
HA
Michaud
Institut de Recherche en Cancérologie de Montpellier; Inserm U896 ; Institut Régional de Lutte contre le Cancer (ICM); Université Montpellier 1 ; Montpellier Cedex, France ; Département d'Immunologie; CHRU Montpellier and Faculté de Médecine; Université Montpellier I ; Montpellier Cedex, France.
Jean-François
JF
Eliaou
Institut de Recherche en Cancérologie de Montpellier; Inserm U896 ; Institut Régional de Lutte contre le Cancer (ICM); Université Montpellier 1 ; Montpellier Cedex, France.
Virginie
V
Lafont
Institut de Recherche en Cancérologie de Montpellier; Inserm U896 ; Institut Régional de Lutte contre le Cancer (ICM); Université Montpellier 1 ; Montpellier Cedex, France ; co-senior authors.
Nathalie
N
Bonnefoy
Institut de Recherche en Cancérologie de Montpellier; Inserm U896 ; Institut Régional de Lutte contre le Cancer (ICM); Université Montpellier 1 ; Montpellier Cedex, France ; co-senior authors.
Laurent
L
Gros
ADCC, antibody-dependent cell cytotoxicity; ADCP, antibody-dependent cell phagocytosis; B-NHL, B-cell non-Hodgkin's lymphoma; CDC, complement-dependent cytotoxicity; CTLA4, cytotoxic T-lymphocyte-associated protein 4; DC, dendritic cell; FDA, food and drug administration; FcRn, neonatal Fc receptor; HMGB1, high-mobility group box 1; ICD, immunologic cell death; IDO, indoleamine 2, 3-dioxygenase; IFNγ, interferon γ; MDSC, myeloid-derived suppressor cell; NK, natural killer; PD-1, programmed cell death 1; TA, tumor antigen; TA-targeting mAbs; Treg, regulatory T cell; combined therapies; immunomodulation; immunosuppressive pathways; mAb, monoclonal antibody; vaccine-like effects