GD2-Targeted Immunotherapy and Radioimmunotherapy

Abstract

Ganglioside GD2 is a tumor-associated surface antigen found in a broad spectrum of human cancers and stem cells. They include pediatric embryonal tumors (neuroblastoma, retinoblastoma, brain tumors, osteosarcoma, Ewing’s sarcoma, rhabdomyosarcoma), as well as adult cancers (small cell lung cancer, melanoma, soft tissue sarcomas). Because of its restricted normal tissue distribution, GD2 has been proven safe for antibody targeting. Anti-GD2 antibody is now incorporated into the standard of care for the treatment of high risk metastatic neuroblastoma. Building on this experience, novel combinations of antibody, cytokines, cells and genetically engineered products all directed at GD2 are rapidly moving into the clinic. In the review, past and present immunotherapy trials directed at GD2 will be summarized, highlighting the lessons learned and the future directions.

Radioimmunotherapy of human tumours

“…GD2 is widely expressed among human tumours including neuroblastoma, bone sarcomas, soft-tissue sarcomas, small-cell lung cancer, retinoblastoma, brain tumours, and tumour stem cells 126 . In neuroblastoma, this antigen is abundant (>10 6 /cell), relatively homogeneous within and between tumours, and rarely lost following GD2-based immunotherapy 126 .…”

“…GD2 is widely expressed among human tumours including neuroblastoma, bone sarcomas, soft-tissue sarcomas, small-cell lung cancer, retinoblastoma, brain tumours, and tumour stem cells 126 . In neuroblastoma, this antigen is abundant (>10 6 /cell), relatively homogeneous within and between tumours, and rarely lost following GD2-based immunotherapy 126 . Anti-GD2 antibodies for the treatment of metastatic neuroblastoma have proven safe even in young patients, with no late toxicities of CNS or peripheral nervous system with up to 20 years of follow-up 127 .…”

Anti-GD2 MABS and Next-Generation mAb-Based Agents for Cancer Therapy

“…injection of GM-CSF appeared superior to a historical control group receiving 3F8 together with intravenous administration of GM-CSF, raising 5-year progression-free-survival from 11% in the intravenous group to 24% in the subcutaneous group [42]. Phase II studies of 3F8 + GM-CSF combination therapy are still ongoing [43].…”

“…Early results from Phase I clinical trials demonstrate low immunogenicity, favorable pharmacokinetics and less dose limiting pain side effects for hu3F8 than for the mu3F8. [43] Anti-O-Acetyl GD2…”

High expression of TRIM29 (ATDC) contributes to poor prognosis and tumor metastasis by inducing epithelial-mesenchymal transition in osteosarcoma

“…The most common sites of osteosarcoma are long bones of the limbs (3), particularly the distal ends of femur and proximal tibia (4). Despite advances in multimodal treatment strategies, including neoadjuvant chemotherapy and surgery, the survival rate of these patients remains abysmal (5). The five-year survival rate for localized osteosarcoma is ~65-70%, while that for metastatic disease is a lowly 20% (6)(7)(8)(9).…”