Abstract IA09: Immunotherapeutic approaches for pediatric solid tumors

Abstract

Abstract For patients with primary metastatic or recurrent soft tissue sarcomas, cytotoxic chemotherapy is currently the primary treatment modality. Despite intensive chemotherapy, the outcome is poor and additional new therapeutic strategies in combination with chemotherapy have to be investigated. Immunotherapy, which involves the patient’s own or a new allogeneic immune system, might have great potential to improve the outcome of affected patients. We have focused on the use of haploidentical transplantation as a form of intensive immunotherapy in order to utilize a graft-versus-solid tumor effect, which might be exerted by donor-derived alloreactive Natural Killer (NK) cells, but also by donor-derived T cells. In a first pilot trial, we have transplanted 26 patients with relapsed neuroblastoma from a haploidentical donor. The transplant-related mortality (TRM) was 0% and the overall survival (OS) was 20%. We then started a protocol using haploidentical transplantation in 68 patients followed post-transplant by 6-9 cycles of the monoclonal anti-GD2 antibody ch14.18CHO. The TRM was 5% and the 3-year OS is 58%. In addition to neuroblastoma, we also hope to apply similar strategies to other pediatric advanced solid tumors including Ewing’s sarcoma, rhabdomyosarcoma, and others. We conclude that haploidentical transplantation of patients with relapsed/refractory solid tumors is a platform on which further immunotherapeutic strategies can be developed, such as antibodies directed against other targets than GD2, such as CD276, or bispecific T-cell engagers (BiTEs), chimeric antigen receptor (CAR) T-cells or CAR NK cells, or antibody/cytokine fusion proteins, and these approaches will be discussed. The main goal of immunotherapy, however, must be to establish a long-term memory immune response against the tumor, and haploidentical transplantation might facilitate such a response. Citation Format: Rupert Handgretinger. Immunotherapeutic approaches for pediatric solid tumors [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr IA09.