Table 1 Comprehensive overview of treatments in neuroblastoma engaging myeloid cells as effector cells
From: Targeting the myeloid microenvironment in neuroblastoma
Therapeutic target | Treatment | Studied population | (Pre-)clinical model | Outcome | Ref |
|---|---|---|---|---|---|
GD2 | Anti-GD2 | PMN | In vitro, ex vivo | Induces ADCC of NB cell lines by healthy and patient-derived PMN, via FcγRII, FcγRIII and Mac-1 | |
GD2 | Anti-GD2 | PMN, other myeloid cells | Clinical trials | PMN-mediated ADCC via FcγRII and FcγRIII, improvement EFS and OS | |
GD2 | Anti-GD2 + GM-CSF | PMN, other myeloid cells | In vitro, clinical trials | GM-CSF increases and activates myeloid cells, increases CD11b expression, enhances PMN-mediated ADCC by anti-GD2 | |
GD2 | Anti-GD2 + G-CSF | PMN | In vitro | Similar to GM-CSF, enhances PMN-mediated ADCC by anti-GD2 | [133] |
GD2 | Anti-GD2 + retinoic acid | PMN | In vitro | Retinoic acid attracts PMN via IL-8 production | [134] |
IL-2R | IL-2 or IL-2-expressing NB cells | Eosinophils | In patients, clinical trials | Increase of eosinophil numbers, elevated IL-5 serum levels | |
GD2 | IgA anti-GD2 | PMN, TAM | In vitro, 9464D syngeneic and IMR32 xenograft models | Superior neutrophil activation compared to IgG anti-GD2 especially with patient-derived PMN, prolonged survival in vivo | |
GD2 + CD47 | Anti-GD2 IgG + anti-CD47 | PMN, TAM | In vitro, multiple mouse models | Enhanced phagocytosis and PMN-mediated killing of NB cells by disrupting CD47/SIRPα axis, prolonged survival in vivo, influx of intratumoral macrophages | |
B7-H3 | B7-H3/GD2 bispecific or anti-B7-H3 ADC | Myeloid cells | PDX models | Efficacy possibly mediated by myeloid cells | |
GPC2 | anti-GPC2 ADC | Monocytes, TAM, MDSC | NXS2 xenograft and 9464D syngeneic models | Recruitment monocytes, TAM and MDSC, phagocytosis of NB cells, prolonged survival |