GD2-GD3 Vaccine / SERB Pharmaceuticals, Memorial Sloan-Kettering Cancer Center, BioNTech - LARVOL DELTA

Flow Cytometry Analysis of Gangliosides Expressed on Extracellular Vesicles. (PubMed, Methods Mol Biol) - "Here, we describe a method for isolating EVs secreted by cells and report a flow cytometry analysis for gangliosides on EVs. By using Tim4-conjugated beads, which bind specifically to EVs, molecules expressed on EVs can be easily detected even with flow cytometry."

Journal

An AI-Driven Multilayer Model of Lung Involvement in NeuronopathicGaucher Disease (nGD) and Management Strategies (SSIEM 2026) - "Management requires a multimodal approach beyond enzyme and substrate reduction therapies. Mechanism-based interventions, including pediatric-appropriate immune modulating and anti-inflammatory agents, aspiration mitigation, and pulmonary hypertension therapy, may improve long-term outcomes in GD2/GD3."

Cardiovascular • Gaucher Disease • Genetic Disorders • Hepatology • Infectious Disease • Inflammation • Metabolic Disorders • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Bivalent Vaccine With Escalating Doses of the Immunological Adjuvant OPT-821, in Combination With Oral ?-glucan for High-Risk Neuroblastoma (clinicaltrials.gov) - P1/2 | N=374 | Completed | Sponsor: Memorial Sloan Kettering Cancer Center | Active, not recruiting ➔ Completed | Trial completion date: May 2027 ➔ Aug 2026 | Trial primary completion date: May 2027 ➔ Aug 2026

Trial completion • Trial completion date • Trial primary completion date • Neuroblastoma • Oncology • Solid Tumor • FCGR3A • MYCN

Bivalent Vaccine With Escalating Doses of the Immunological Adjuvant OPT-821, in Combination With Oral β-glucan for High-Risk Neuroblastoma (clinicaltrials.gov) - P1/2 | N=374 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: May 2026 ➔ May 2027 | Trial primary completion date: May 2026 ➔ May 2027

Trial completion date • Trial primary completion date • Neuroblastoma • Oncology • Solid Tumor • FCGR3A • MYCN

Dynamic tracking of GD3 to GD2 Gangliosides in T lymphoblasts via Nuclear Magnetic Resonance Spectroscopy. (PubMed, Glycobiology) - "Complementary 1H NMR analysis directly applied to cellular extracts identified diagnostic anomeric proton signals corresponding to GD3 at day 4 and GD2 at day 6, confirming the structural transition. This dual-platform approach demonstrates, for the first time, the NMR-mediated discrimination of GD3 and GD2 in unpurified human cell extracts, providing robust evidence of ganglioside remodeling during MOLT-4 cell proliferation and establishing a valuable methodology for functional and therapeutic studies involving gangliosides."

Journal • Hematological Malignancies • Leukemia • Oncology

Transcriptomic signatures in Gaucher disease subtypes: A systems biology perspective. (PubMed, Mol Genet Metab Rep) - "Top 5 % DEGs, including KDM5D (GD1), MMP1 (GD2), and FOSB (GD3), were proposed as subtype-specific markers. The findings highlighted distinct molecular signatures between GD1 (immune/ECM-focused) and GD2/GD3 (neuroinflammatory/neurodevelopmental), informing targeted diagnostics."

Journal • Gaucher Disease • Genetic Disorders • Inflammation • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases • AKT1 • COL4A1 • CXCL8 • GBA • IL4 • IL6 • KDM5D • LAMP2 • MMP1 • MX1 • PACERR • POSTN • PTGS2 • TGFB1 • TGFBR2 • TP53

Bivalent Vaccine With Escalating Doses of the Immunological Adjuvant OPT-821, in Combination With Oral β-glucan for High-Risk Neuroblastoma (clinicaltrials.gov) - P1/2 | N=374 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: May 2025 ➔ May 2026 | Trial primary completion date: May 2025 ➔ May 2026

Trial completion date • Trial primary completion date • Neuroblastoma • Oncology • Solid Tumor • FCGR3A • MYCN

Correlation of GD2 Biosynthesis Enzymes With Cancer Stem Cell Markers in Human Breast Cancer. (PubMed, Cancer Genomics Proteomics) - "These findings lend further support to the growing evidence that GD2 is a potential biomarker of CSCs and epithelial-mesenchymal transition (EMT) in human breast cancer that can be amenable to therapeutic targeting."

Biomarker • Journal • Brain Cancer • Breast Cancer • CNS Tumor • Glioblastoma • Melanoma • Neuroblastoma • Oncology • Solid Tumor • B4GALNT1 • BMI1 • CD24 • CXCR1 • ITGA6 • ITGB1 • NES • NGFR • PDPN • POU5F1 • PSCA

Ganglioside expression delineates human mesenchymal stem/stromal cell populations derived from different tissue sources. (PubMed, Cytotherapy) - "Importantly, expression of GD3, GD2, and SSEA-4 is markedly diminished on differentiation of BM-MSCs, and co-cultures of A-MSCs and BM-MSCs show that the expression of GD3, GD2, and SSEA-4 is a cell-intrinsic feature of BM-MSCs. These data stratify the glycosignature(s) of human MSCs derived from different tissue sources, provide direct evidence that expression of these structures is cell stage-/lineage-specific, unveil the mechanistic basis of the differential expression of these glycan determinants, and draw attention to how knowledge of the MSC glycosignature can impact cytotherapeutic strategies."

Journal

GD2 in Breast Cancer: A Potential Biomarker and Therapeutic Target. (PubMed, Cancer Genomics Proteomics) - "Therapeutic targeting of GD2 with monoclonal antibodies (moABs) like dinutuximab and naxitamab has demonstrated anti-cancer activity in preclinical cancer models and human clinical trials against high-risk neuroblastoma reducing tumor growth and enhancing survival...This narrative review article underscores the critical role of GD2 in breast cancer pathogenesis and highlights the promising therapeutic opportunities it offers. It advocates for the initiation of clinical trials to further explore the potential of GD2-targeted treatment in combination with standard breast cancer therapies."

Biomarker • Journal • Review • Breast Cancer • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • Triple Negative Breast Cancer

GUT MICROBIOTA ASSOCIATIONS WITH GD2/GD3 VACCINE RESPONSE IN PATIENTS WITH HIGH-RISK NEUROBLASTOMA (SIOP 2024) - P1/2 | "Lastly, exposure to moderate/high perturbation antibiotics (to which many Clostridia are sensitive) was associated with worse PFS (HR 1.75, 95% CI 0.95-3.24) though p=0.07.Conclusions Patients with HR-NB with higher fecal abundance of taxa within the Clostridia class mounted better antibody response to GD2/GD3 vaccine and had favorable PFS. The immunobiology behind this association and the impact of microbiome modulation on improving outcomes deserves further investigation."

Clinical • Gut Microbiota • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor

Long Prime-Boost Interval and Heightened Anti-GD2 Antibody Response to Carbohydrate Cancer Vaccine. (PubMed, Vaccines (Basel)) - "The carbohydrate ganglioside GD2/GD3 cancer vaccine adjuvanted by β-glucan stimulates anti-GD2 IgG1 antibodies that strongly correlate with improved progression-free survival (PFS) and overall survival (OS) among patients with high-risk neuroblastoma...The association between IgG1 titer during re-enrollment and β-glucan receptor dectin-1 SNP rs3901533 was significant (p = 0.01). A longer prime-boost interval could significantly improve antibody responses in patients treated with ganglioside conjugate cancer vaccines."

Journal • CNS Tumor • Neuroblastoma • Oncology • Pain • Solid Tumor • CLEC7A

GD2 and its biosynthetic enzyme GD3 synthase promote tumorigenesis in prostate cancer by regulating cancer stem cell behavior. (PubMed, Sci Rep) - "Variable levels of cell surface GD2 expression were seen on many PC cell lines, and the expression was highly upregulated by experimental induction of lineage progression or enzalutamide resistance in CRPC cell models...CRISPR-Cas9 knockout (KO) of the rate-limiting GD2 biosynthetic enzyme GD3 Synthase (GD3S) in GD2high CRPC cell models markedly impaired the in vitro oncogenic traits and growth as bone-implanted xenograft tumors and reduced the cancer stem cell and epithelial-mesenchymal transition marker expression. Our results support the potential role of GD3S and its product GD2 in promoting PC tumorigenesis by maintaining cancer stem cells and suggest the potential for GD2 targeting in advanced PC."

Cancer stem • Journal • Castration-Resistant Prostate Cancer • CNS Tumor • Genito-urinary Cancer • Neuroblastoma • Oncology • Prostate Cancer • Solid Tumor

GD2 and GD3 gangliosides as a diagnostic biomarkers for all stages and subtypes of ovarian cancer (BGCS 2023) - "Conclusions A diagnostic model combining GD2/GD3 quantification in serum had diagnostic power for all subtypes and all stages of OC, including early-stage. Future work will aim to validate these biomarkers in independent prospective studies."

Biomarker • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • MUC16

Bivalent Vaccine With Escalating Doses of the Immunological Adjuvant OPT-821, in Combination With Oral β-glucan for High-Risk Neuroblastoma (clinicaltrials.gov) - P1/2 | N=374 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: May 2023 ➔ May 2025 | Trial primary completion date: May 2023 ➔ May 2025

Combination therapy • Trial completion date • Trial primary completion date • CNS Tumor • Neuroblastoma • Neuroendocrine Tumor • Oncology • Solid Tumor • FCGR3A • ITGB2 • MYCN

GD2 and GD3 gangliosides as diagnostic biomarkers for all stages and subtypes of epithelial ovarian cancer. (PubMed, Front Oncol) - "A diagnostic model that included serum levels of GD2+GD3+age was superior to the standard of care (CA125, p<0.001) in diagnosing OC and early-stage (I/II) OC...A diagnostic model combining GD2 and GD3 quantification in serum had diagnostic power for all subtypes and all stages of OC, including early stage. Further research exploring the utility of GD2 and GD3 for diagnosis of OC is warranted."

Biomarker • Journal • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • MUC16

GUT MICROBIOTA ASSOCIATIONS WITH GD2/GD3 VACCINE RESPONSE IN PATIENTS WITH HIGH-RISK NEUROBLASTOMA (ASPHO 2023) - P1/2 | "Patients with HR-NB with higher fecal abundance of Clostridia taxa mounted greater antibody response to GD2/GD3 vaccine and had favorable PFS. The immunobiology behind this association as well as the impact of gut microbiome modulation in improving clinical outcomes deserves further investigation."

Clinical • Gut Microbiota • IO biomarker • CNS Tumor • Neuroblastoma • Neuroendocrine Tumor • Oncology • Solid Tumor • Transplantation

The biological role and immunotherapy of gangliosides and GD3 synthase in cancers. (PubMed, Front Cell Dev Biol) - "Many clinical trials targeting GD2 are ongoing and various immunotherapy studies targeting gangliosides and GD3S are gradually attracting much interest and attention. This review summarizes the function, molecular mechanisms, and ongoing clinical applications of GD3, GD2, and GD3S in abundant types of tumors, which aims to provide novel targets for future cancer therapy."

IO biomarker • Journal • Review • Oncology

Y-mAbs Announces Restructuring Plan and Provides Financial Outlook Following Complete Response Letter from FDA (GlobeNewswire) - "Y-mAbs Therapeutics...announced a strategic restructuring plan designed to extend its cash runway and prioritize resources on the commercialization and potential label extension of DANYELZA and development of the SADA (Self-Assembly DisAssembly ('SADA') PRIT 2-STEP) technology platform....The Company has assumed a deprioritization of the omburtamab program, including all indications, in designing its restructuring plan and in its estimates for 2023. In addition, the Company plans to deprioritize other pipeline programs, including activities relating to GD2-GD3 Vaccine and CD33 bispecific antibody constructs....'We anticipate a Type A meeting with the FDA in January 2023 to discuss the future of omburtamab'....Targeting an IND submission in Q2 2023 for CD38-SADA construct against non-Hodgkin's lymphoma to potentially validate SADA in blood cancers....Estimated DANYELZA net product revenues for the 2023 fiscal year are expected to be between $60-65 million."

FDA event • IND • Pipeline update • Sales projection • Neuroblastoma • Oncology • Solid Tumor

Effect of Oral β-Glucan on Antibody Response to Ganglioside Vaccine in Patients With High-Risk Neuroblastoma: A Phase 2 Randomized Clinical Trial. (PubMed, JAMA Oncol) - P1/2 | "Among patients with high-risk relapsed metastatic neuroblastoma, oral β-glucan adjuvant during GD2/GD3 ganglioside vaccine boost has stimulated IgG antibody response, which was associated with improved survival; however, the effectiveness of oral β-glucan during the vaccine priming phase remains unproven...Alternative or additional adjuvants may be needed to enhance seroconversion. ClinicalTrials.gov Identifier: NCT00911560."

Clinical • Journal • P2 data • CNS Tumor • Neuroblastoma • Neuroendocrine Tumor • Oncology • Solid Tumor • CLEC7A

Oral beta-glucan enhanced anti-ganglioside antibody titer after vaccination against high-risk neuroblastoma: Results of a randomized trial (AACR 2022) - P1/2 | "Background and Aim: Ganglioside GD2/GD3 vaccine stimulated robust antibody response among patients with high-risk metastatic neuroblastoma (HR-NB) who had prior disease progression (J Clin Oncol 39:215-226, 2020)... Adding oral yeast beta-glucan as vaccine adjuvant during the first 6 weeks of immunization significantly enhanced the anti-GD2-IgG1 antibody response without added toxicities. Its impact on patient survival will require a longer clinical follow-up."

Clinical • Neuroblastoma • Oncology • Solid Tumor

Anti-GD2 Directed Immunotherapy for High-Risk and Metastatic Neuroblastoma. (PubMed, Biomolecules) - "The use of anti-GD2/GD3 tumor vaccine is a novel and potential approach to minimizing late relapse. How to induce GD2 expression from tumor cells using the epigenetic approach is a hot topic nowadays. We expect that anti-GD2 treatment can serve as a model for the use of monoclonal antibody immunotherapy against cancers in the future."

IO biomarker • Journal • Review • Neuroblastoma • Oncology • Solid Tumor • CSF2 • IL2

Tumor microenvironment modulates ganglioside expression leading to immunosuppression in triple negative breast cancer (SABCS 2021) - "In this study, we hypothesize that tumor-microenvironment influences expression of gangliosides downstream of GD3S, including GD2/GD3, suppressing the anti-tumor immune response while inhibiting GD3S expression enhances immune-mediated killing of TNBC cells...In conclusion, GD2 is a tumor-specific marker in patients with TNBC and that GD3S overexpression is associated with T-cell exhaustion and maintenance of an immunosuppressive microenvironment in breast cancer. This immunosuppressive microenvironment in TNBCs fostered by gangliosides downstream of GD3S is also a manifestation of the cross-talk between tumor and tumor-associated stromal cells."

Biomarker • IO biomarker • Tumor microenvironment • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CTLA4 • LAG3 • PD-1

Multiple Immunofluorescence Imaging Analysis Reveals Differential Expression of Disialogangliosides GD3 and GD2 in Neuroblastomas. (PubMed, Pediatr Dev Pathol) - "We demonstrated that neuroblastomas from low-risk patients included more GD3-positive and GD2-negative cells than those from high-risk patients. Clarifying the heterogeneity of neuroblastoma aids in better understanding the biological characteristics and clinical behavior."

Journal • Immunology • Infectious Disease • Neuroblastoma • Oncology • Solid Tumor

Ganglioside GD2: a novel therapeutic target in triple-negative breast cancer. (PubMed, Ann N Y Acad Sci) - "The ganglioside GD2 has been shown to be upregulated in primary TNBC tumors compared with normal breast tissue and has been shown to identify BCSCs. In this review, we discuss GD2 as a BCSC- and tumor-specific marker in TNBC; epithelial-to-mesenchymal transition and the signaling pathways that are upstream and downstream of GD2 and the role of these pathways in tumorigenesis and metastasis in TNBC; direct and indirect approaches for targeting GD2; and ongoing clinical trials and treatments directed against GD2 as well as future directions for these strategies."

Journal • Review • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD24 • CD44