TABLE 1.

Clinical trials targeting GD2.

Immunotherapy methods	Cancer types	Trail ID	Study outcomes/results	Reference
Isotretinoin and ch14.18 combined with GM-CSF or IL-2 (immunotherapy) vs. Isotretinoin only (standard therapy)	HR-NB	NCT00026312	Immunotherapy vs. standard therapy	Yu et al. (2010)
			1. Two-year EFS: 66% ± 5% vs. 46% ± 5%; (p = 0.01)
			2. OS: 86% ± 4% vs. 75% ± 5% at 2 years; (p = 0.02)
I/T/TEM vs. I/T/DIN	R/R NB	NCT01767194	Objective response: 1 of 18 patients (5.6%; 95%CI 0.0%–16.1%) vs. 9 of 17 patients (53%; 95%CI 29.2%–76.7%)	Mody et al. (2017)
Dinutuximab beta plus subcutaneous IL-2 vs. Dinutuximab beta alone	HR-NB	NCT01704716	1. Three-year EFS: 60% (95% CI 53–66) vs. 56% (95% CI 49–63)	Ladenstein et al. (2018)
			2. Toxicities: More cardinal toxicities and grade 3–4 impaired general conditions with dinutuximab beta plus subcutaneous IL-2 treatment
Hu14.18-IL2, GM-CSF plus isotretinoin	R/R NB	NCT01334515	1. Objective response: stratum 1 (n = 14) with no response; in stratum 2, 5 of 31 patients with objective response (3 of 5 patients with response beyond 5 years)	Shusterman et al. (2019)
			2. Toxicities: 4 of 51 evaluable patients for tolerability developed unacceptable toxicities; no grade 3/4 neurologic toxicities
Haplo HSCT plus dinutuximab beta	Relapsed Stage IV NB	NCT02258815	1. Haplo HSCT established a strong cellular immune system in heavily pretreated patients	Seitz et al. (2021)
			2. Dinutuximab beta improved the NK-cell function of cytokine secretion, degranulation and cytotoxicity
GD2/GD3 vaccine plus β-glucan	HR-NB with a history of PD	NCT00911560	6 months vs. 2 years vs. 5 years	Cheung et al. (2021)
			1. PFS: 76.5% ± 4.2% vs. 45.3% ± 5.0% vs. 32.2% ± 6.4%
			2. OS: 99% ± 1.0% vs. 88.4% ± 3.3% vs. 70.7% ± 6.7%
Dinutuximab plus irinotecan vs. irinotecan vs. topotecan	R/R SCLC	NCT03098030	1. Median OS: 6.9 vs. 7.0 vs. 7.4 months (p = 0.3132)	Edelman et al. (2022)
			2. Median PFS: 3.5 vs. 3.0 vs. 3.4 months (p = 0.3482)
			3. ORR: 17.1% vs. 18.9% vs. 20.2% (p = 0.8043)
			4. CBR: 67.4% vs. 58.9% vs. 68.1% (p = 0.0989)
CAR-CTLs and CAR-ATCs	NB with/without active disease	NCT00085930	1. OS: A longer OS for patients with no evidence of active disease than those with active disease (p = 0.04)	Louis et al. (2011)
			2. Low level of CAR-ATCs or ACR-CTLs lasting 6 weeks or more was correlated with substantially TTP
			3. Three Of 11 patients with active disease derived complete response, 2 of which had persisted complete response for >60 months and >21 months
Anti-GD2 CAR-NKT cells plus Cy/Flu	R/R NB	NCT03294954	One of 3 patients had objective response with regression of bone metastatic lesion	Heczey et al. (2020)
GD2 CAR-T cells	DIPG or DMG	NCT04196413	1. Three of 4 patients obtained clinical and radiographic benefits with i.v. Administration of GD2 CAR-T cells	Majzner et al. (2022)
			2. Three of 3 treated patients received the i.c.v. Administration and derived extra radiographic and/or clinical benefits
			3. i.c.v. vs. i.v. Administration: less CRS, elevated pro-inflammatory cytokines and reduced immunosuppressive cells in CSF with i.c.v. Administration
			4. No sign or symptom of on-target and off-tumor toxicity

Abbreviations: GM-CSF, granulocyte-macrophage colony-stimulating factor; IL-2, interleukin 2; HR-NB, high-risk neuroblastoma; EFS, event-free survival; OS, overall survival; I/T/TEM, irinotecan-temozolomide-temsirolimus; I/T/DIN, irinotecan-temozolomide-dinutuximab; R/R NB, refractory or relapsed neuroblastoma; PD, Parkinson’s disease; R/R SCLC, relapsed/refractory SCLC; haplo HSCT, haploidentical hematopoietic stem cell transplantation; PFS, progression-free survival; ORR, objective response rate; CBR, clinical benefit rate; CAR, chimeric antigen receptor; CAR-CTLs, CAR-cytotoxic T lymphocytes; CAR-ATCs, CAR-autologous activated T cells; DIPG, diffuse intrinsic pontine glioma; DMG, diffuse midline gliomas; i.v, intravenous; i.c.v, intracerebroventricular.