Review Article

Neuroblastoma Origin and Therapeutic Targets for Immunotherapy

Table 1

Currently active clinical trials for neuroblastoma immunotherapy.

Anti-GD2 immunotherapy
ApproachAgent combinationPhaseNCT identifierStart year

Naked antibody (murine 3F8)3F8, allogeneic NK cells, cyclophosphamide, vincristine, topotecanINCT008771102009
3F8, GM-CSF, isotretinoinIINCT01183897, NCT011838842010
N/ANCT021009302014

Naked antibody (chimeric dinutuximab)Dinutuximab, irinotecan, temozolomideIINCT017671942013
Dinutuximab, autologous NK cells, lenalidomideINCT025738962015
Dinutuximab, 131I-metaiodobenzylguanidineINCT033326672017

Naked antibody (chimeric dinutuximab-beta, produced in CHO)Dinutuximab-beta, IL-2, isotretinoinIIINCT017047162012
Dinutuximab-betaIINCT027434292016
Dinutuximab-beta, nivolumabINCT029144052016
Dinutuximab-beta, haploidentical NK cells, IL-2, cyclophosphamideI/IINCT032426032017

Naked antibody (humanized hu3F8)hu3F8INCT014198342011
hu3F8, GM-CSFI/IINCT017576262012
IIINCT033633732017
hu3F8, IL-2INCT016628042012
hu3F8, haploidentical NK cells, IL-2, cyclophosphamideINCT026506482016
hu3F8, GM-CSF, isotretinoinIINCT030333032017
hu3F8, irinotecan, temozolomide, GM-CSFPilotNCT031897062017

Naked antibody (humanized hu14.18)hu14.18K322A, allogeneic NK cells, IL-2, GM-CSF, combination chemotherapyINCT015766922012
hu14.18K322A, allogeneic NK cells, IL-2, G-CSF, GM-CSF, combination chemotherapyIINCT018579342013

Immunocytokinehu14.18-IL2, haploidentical NK cellsINCT032098692017

Radioimmunoconjugate131I-3F8IINCT004459652007

T cell engaging bispecific antibodyhu3F8-scBA, activated T cells, GM-CSF, IL-2I/IINCT021730932014

Adoptive NK cell transferHLA-haploidentical HCT, allogeneic NK cellsIINCT021008912014

Adoptive NKT cell transferAutologous anti-GD2 NKT cells expressing IL-15, cyclophosphamide, fludarabineINCT032949542017

Adoptive T cell transferAutologous anti-GD2 3rd-gen iC9 CAR-modified T cells, pembrolizumab, cyclophosphamide, fludarabineINCT018226522013
Autologous anti-GD2 4th-gen iC9 CAR-modified T cellsIINCT027652432016
Autologous anti-GD2 2nd-gen CAR-modified T cells, cyclophosphamide, fludarabineINCT027619152016
Autologous anti-GD2 iC9 CAR-modified T cellsI/IINCT033730972017

VaccineGene-modified SJNB-JF-IL2 and SJNB-JF-LTN in conjunction with unmodified SKNLP (neuroblastoma cell vaccine)I/IINCT007032222008
Bivalent GD2/GD3 lactone vaccine with OPT-821 adjuvant, oral β-glucanI/IINCT009115602009
Gene-modified SJNB-JF-IL2 and SJNB-JF-LTN in conjunction with unmodified SKNLP (neuroblastoma cell vaccine), oral cyclophosphamideI/IINCT011925552010

Anti-CD171 immunotherapy

Adoptive T cell transferAutologous anti-CD171 CAR-modified T cells (2nd- and 3rd-gen) expressing EGFRtINCT023116212014

Anti-NGcGM3 immunotherapy

Naked antibody (anti-idiotype vaccine, murine)RacotumomabIINCT029989832016

Anti-B7-H3 immunotherapy

Radioimmunotherapy (murine 131I-8H9)131I-conjugated omburtomabINCT000892452004
131I-conjugated omburtomabII/IIINCT032754022017

Anti-NY-ESO-1 immunotherapy

Adoptive T cell transferAutologous anti-NY-ESO-1 CAR-modified T cellsINCT024576502015

Active, not recruiting (from http://clinicaltrials.gov). CAR: chimeric antigen receptor; EGFRt: truncated epidermal growth factor receptor; HCT: hematopoietic cell transplantation; HLA: human leukocyte antigen; hu3F8-scBA: anti-GD2/anti-CD3 (hu3F8): single chain bispecific antibody; iC9: inducible caspase 9 suicide gene.