The Immunotherapy subcommittee convened in Jerusalem during SIOPEN AGM to discuss and better define immunotherapy perspectives for SIOPEN. The committee is largely increasing in members now counting 37 experts in the field of high risk neuroblastoma and immunotherapy.
Sadly, Vito Pistoia, a highly recognised immunologist with seminal contributions in the field of translational immunotherapy of neuroblastoma, died in September 2018. He was a founder member of the Immunotherapy subcommittee and his .expertise and contributionwill be missed.
Following a detailed review of the current landscape of immunotherapeutic approaches in neuroblastoma the group worked towards immediate and long-term proposals to be addressed in the preclinical and clinical arena.
Topics covered the current landscape of CAR-T cell approaches in neuroblastoma, perspectives with novel immunotherapy agents and combinations, current concepts in stem cell immunotherapy, as well as aspects in immune monitoring of clinical trials soon to open in SIOPEN. Main results and conclusions included that the major activities in the United States, China, Australia and Europe with CAR-T cells in neuroblastoma are encouraging. However the lack the strong activity signal compared to pediatric leukemia emphasises the need to further optimized the approach on several levels ranging from CAR design to evaluation of other antigens (ALK, B7H3, GCP2) as well as questions related to manufacturing. The approach with hu3F8 and GD2/GD3 bivalent vaccines were also discussed in the group, based on published data and information available from recent meetings. However it was difficult to clearly define the position of these agents in view of the SOIPEN development strategy, which needs further exploration. Signals from clinical using haploidentical stem cell transplantation suggest an allogeneic anti-tumor effect augmented by anti-GD2 antibody, however there is no randomized trial to clearly identify this effect. A trial proposal was presented, which was considered highly interesting, and further refinement related to the control arm are next steps. Finally, the implementation of the analysis of tumor microenvironment in planed immunotherapy trials by analysis of immune signatures of tumor-cells and stroma cells was identified as an immediate topic to further elaborate in a joint meeting with the Biology Group at the spring meeting 2019.
Mueller, I., et al. (2018). "Tolerability, response and outcome of high-risk neuroblastoma patients treated with long-term infusion of anti-GD2 antibody ch14.18/CHO." MAbs 10(1): 55-61.
Ladenstein R et al “Randomised use of Interleukin-2 with anti-GD2 anntibody ch14.18/CHO in High Risk Neuroblastoma patients. Results of HR-NBL-1 /SIOPEN study” Lancet Oncology. Accepted for publication
Siebert N et al. ”Impact of HACA on immunomodulation and treatment toxicity following ch14.18/CHO long-term infusion with interleukin-2: results from a SIOPEN phase 2 trial” Cancers Accepted for publication October 2018
The presence of guests from COG (Paul Sondel; Julie Park) during the immunotherapy subcommittee meeting was enriching the discussion within SOIPEN by sharing transatlantic perspectives related to immunotherapy of neuroblastoma.