Effector mechanisms of IgA antibodies against CD20 include recruitment of myeloid cells for antibody‐dependent cell‐mediated cytotoxicity and complement‐dependent cytotoxicity

Antibody Isotypes for Tumor Immunotherapy

“…Antibodies of the IgA isotype were particularly effective in recruiting myeloid effector cells (monocytes/macrophages and granulocytes) for ADCC [38,39,40] while natural killer cells (NK cells) are not activated by IgA antibodies. Physiologically, IgA antibodies are the first line of immune defense against pathogens at mucosal surfaces [41].…”

“…In addition to their potent activity in recruiting myeloid effector cells for ADCC, IgA antibodies against CD20 triggered CDC against lymphoma cells [40]. Fab-mediated effector functions of monomeric IgA antibodies were similar to IgG antibodies, but were enhanced when dimeric IgA antibodies were compared with monomeric molecules [38].…”

“…To overcome this limitation, an Fc-engineered IgA2 molecule was developed, which demonstrated improved stability and a longer serum half-life translating into higher in vivo efficacy of the engineered compared to the parental IgA molecule [43]. Also IgA antibodies against human epidermal growth factor receptor 2/neu (HER2/neu) or CD20 demonstrated in vitro and in vivo efficacy [40,44]. Despite these promising preclinical activities, IgA antibodies have currently not been introduced into clinical studies.…”

Monoclonal antibody‐mediated killing of tumour cells by neutrophils

“…Moreover, immature bone marrow neutrophils were able to kill tumour cells after targeting FcαRI, but were ineffective when FcγRI was triggered . The superior ability of FcαRI to trigger neutrophil‐mediated tumour cell killing has now been demonstrated for a plethora of tumour cells and antigens (eg, Ep‐CAM (colon carcinoma), HER‐2 (mamma carcinoma), EGFR (epithelial, colorectal and renal cell carcinoma), carcinoembryonic antigen, CD30 (B‐ and T‐cell lymphoma), HLA class II and CD20 (B‐cell lymphoma)) . An anti‐EGFR dimeric IgA variant initiated neutrophil‐mediated tumour killing and was also transported by the polymeric Ig receptor that is expressed on epithelial cells, which may be useful when targeting mucosal tumours .…”

“…40 The superior ability of FcaRI to trigger neutrophil-mediated tumour cell killing has now been demonstrated for a plethora of tumour cells and antigens (eg, Ep-CAM (colon carcinoma), HER-2 (mamma carcinoma), EGFR (epithelial, colorectal and renal cell carcinoma), carcinoembryonic antigen, CD30 (B-and T-cell lymphoma), HLA class II and CD20 (B-cell lymphoma)). 16,[41][42][43][44] An anti-EGFR dimeric IgA variant initiated neutrophil-mediated tumour killing and was also transported by the polymeric Ig receptor that is expressed on epithelial cells, which may be useful when targeting mucosal tumours. 45 Interestingly, FcaRI is the only neutrophil Fc receptor that after cross-linking induces the release of leukotriene B4, which is a potent chemoattractant for neutrophils.…”