Ex vivo expanded patient-derived ?? T-cell immunotherapy enhances neuroblastoma tumor regression in a murine model.

ABSTRACT: An effective therapy regimen for relapsed/refractory high-risk neuroblastoma (NB) includes the anti-GD2 monoclonal antibody, dinutuximab, in combination with temozolomide and irinotecan, supporting a role for chemo-immunotherapy in NB. ?? T cells are an attractive anti-tumor immunotherapy because of their direct cytotoxic activity mediated through cell surface receptors NKG2D and CD16. NKG2D facilitates the innate recognition of stress-induced ligands whereas CD16 recognizes antibody bound to tumors and activates mechanisms of antibody-dependent cellular cytotoxicity (ADCC). This study demonstrates an efficient method for expanding and storing ?? T cells from NB patient-derived apheresis products at clinically relevant amounts. The expanded patient-derived ?? T cells were cytotoxic against the K562 cell line and multiple NB cell lines. Combining ?? T cells with dinutuximab led to a 30% increase in tumor cell lysis compared to ?? T cells alone. Furthermore, low-dose temozolomide in combination with expanded ?? T cells and dinutuximab resulted in increased IFN? secretion and increased ?? T-cell surface expression of FasL and CD107a. IMR5 NB cell line xenografts established subcutaneously in NSG mice were treated with a regimen of dinutuximab, temozolomide, and ?? T cells. This combination caused targeted killing of NB xenografts in vivo, reducing tumor burden and prolonging survival. These data support the continued preclinical testing of dinutuximab and temozolomide in conjunction with ?? T-cell immunotherapy for patients with recurrent/refractory NB.

SUBMITTER: Zoine JT 

PROVIDER: S-EPMC6682349 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature