Tumor necrosis factor receptor superfamily member 8 (CD30) and Low affinity immunoglobulin gamma Fc region receptor III-A (CD16A) immune synapse (CD30-CD16A)

The CD30–CD16A immune synapse is a specialized intercellular junction formed between CD30-expressing neoplastic cells and CD16A-expressing innate effector cells, such as natural killer (NK) cells and macrophages (Reusch et al., 2014). This synapse is typically induced by bispecific antibodies or innate cell engagers (ICEs) like AFM13 (acimtamig), which simultaneously bind to the CD30 antigen (TNFRSF8) on lymphoma cells and the CD16A receptor (FCGR3A) on effector cells (Affimed, 2023). The formation of this synapse facilitates the close proximity required for the effector cell to release cytotoxic granules, such as perforin and granzymes, or to initiate antibody-dependent cellular phagocytosis (ADCP), leading to the targeted destruction of the tumor cell (Sawas et al., 2019). This mechanism, primarily driving antibody-dependent cellular cytotoxicity (ADCC), bypasses the need for MHC-restricted T-cell activation, making it a potent strategy for treating CD30-positive malignancies like Hodgkin lymphoma and peripheral T-cell lymphoma (Rothe et al., 2015). By specifically recruiting NK cells via the high-affinity CD16A binding site, these therapies aim to enhance the innate immune response against cancer while minimizing the systemic toxicity often associated with non-specific immune activation or traditional chemotherapy (Affimed, 2023). The stability and quality of this immune synapse are critical determinants of the therapeutic efficacy of bispecific engagers in the clinical setting.

Other names

CD30-CD16A complexCD30/CD16A bispecific engagementAFM13-mediated immune synapseCD30-CD16A bridge

Bispecific engagement of CD30 on tumor cells and CD16A on NK cells and macrophages to induce antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).