Local immune effector cells – functional modulation

Local immune effector cells – functional modulation is a broad therapeutic classification used in the immuno-oncology field to group agents that enhance the activity of immune cells already present at the disease site, primarily the tumor microenvironment. This category is not a single molecular target but encompasses various receptors and pathways that regulate the effector functions of T cells and natural killer (NK) cells [1, 2]. Key molecular targets within this group include members of the tumor necrosis factor receptor superfamily (TNFRSF), such as 4-1BB (CD137), OX40 (CD134), GITR, and CD27, which provide essential co-stimulatory signals for lymphocyte activation and survival [3]. Drugs targeting these molecules are often agonistic monoclonal antibodies designed to trigger these pathways, thereby boosting the anti-tumor immune response and overcoming local immunosuppression [1]. While promising, the clinical development of these modulators has been complicated by the need to achieve sufficient local activation without inducing severe systemic toxicities, such as hepatotoxicity or cytokine release syndrome [2, 3]. This classification is instrumental for analysts to track the diversity of mechanisms being explored to revitalize the exhausted immune landscape in cancer patients [1]. Citations: [1] Tang J, et al. (2018) Nature Reviews Drug Discovery. [2] Cancer Research Institute (2023) IO Landscape Report. [3] Upadhaya S, et al. (2020) Nature Reviews Drug Discovery.

Other names

Immune effector cell functional modulationLocal immune modulationCRI IO Target Category: Local immune effector cellsModulation of local immune effectors

Drugs in this category function by modulating (typically agonistically) co-stimulatory or co-inhibitory receptors on immune effector cells, such as CD8+ T cells and natural killer (NK) cells, to enhance their anti-tumor activity and survival within the local tumor microenvironment [1, 3].