Table 1.
Immunotherapy of pediatric bone cancers.
| Approach | Goal | Target | Therapeutic Agent | Major Obstacles | Refs |
|---|---|---|---|---|---|
| Immune checkpoint inhibitors | Reactivating and amplifying preexisting antitumor immunity |
PD-1 | Nivolumab/OPDIVO®
Pembrolizumab/ Keytruda® |
Low expression, low mutational burden, Immunological cold TME |
[19,43,44,45,46,47,48,49,50,51,52,53,54,55] |
| PD-L1 | Atezolizumab/Tecentriq® | ||||
| CTLA-4 | IpilimumabYERVOY® | ||||
| Tumor specific antigens (TSAs) | Direct tumor targeting | GD2 | Dinutuximab/Unituxin®
anti-GD2 CAR-T cells anti-GD2 CAR-engineered NK cells |
Variable expression in EwS and OS Upregulation of HLA-G checkpoint |
[28,29,30,56] |
| IGF1R | Ganitumab, Dalotuzumab |
Activation of compensatory mechanisms, Toxicity |
[57] | ||
| HER2 | Trastuzumab/Herceptin® | Not expressed in EwS, no clinical benefit for OS | [18,45] | ||
| B7-H3 | Anti-B7-H3 CAR T cells | [27] | |||
| Antitumor vaccines |
Direct tumor targeting | Tumor TSAs or proteins | Dendritic cell vaccine | Need for autologous DCs, Labor-intensive and costly cell isolation | [58] |
| Activation of DC responses | Multiple tumor antigens |
Attenuated tumor cells, could be pulsed with GM-CSF, IL-2 or IL-7 or siRNAs | Immunosuppressive TME, low tumor immunogenicity |
[22] | |
| Oncolytic viruses |
Increase tumor immunogenicity Induce immunogenic cell death |
Tumor | Vaccinia virus/Pexa-Vec Reovirus/Reolysin HSV-1/HSV1716 Adenovirus X-Vir |
Antiviral immunity, Low delivery efficacy, Immunosuppression, T cell exhaustion |
[34,59,60,61,62] |
| Targeting immunosuppressive TME |
Macrophage activation | TME | L-MTP-PE/Mifamurtide, BCG, Coley’s toxins, oncolytic viruses | [63,64] | |
| Macrophage polarization | TME | All-trans retinoic acid (ATRA) | Low delivery efficacy | [65] | |
| Macrophage/MDSC depletion | TME | All-trans retinoic acid (ATRA) Trabectedin |
Toxicity | [66,67,68,69] |