Tumor cell hybridoma vaccine for recurrent neuroblastoma and Ewing sarcoma

Our laboratory and clinical research work is currently focused on vaccine therapy targeting the cancer testis (CT) antigens MAGE-A1, MAGE-A3, and NY-ESO-1. Studies in our laboratory indicate that expression of each of these antigens can be upregulated on most GBM, neuroblastoma, sarcoma, and leukemia cells by exposing tumors to low dose decitabine (DAC), a demethylating agent. With this information we have initiated a phase 1/2 clinical trial in which low dose DAC is given to children with relapsed or therapy refractory neuroblastoma, Ewing sarcoma or rhabdomyosarcoma, followed by an autologous dendritic cell (DC)/ MAGE-A1, MAGE-A3, and NY-ESO-1 vaccine.  This study is meeting its accrual goals, and we have seen some clinical and immunologic responses. We are also initiating a phase 1/2 study in AML patients post-transplant, using low-dose DAC and a DC/CT antigen vaccine to prevent relapse. Considering the fact that these antigens are also upregulated on other malignancies such as glioblastoma multiforme (GBM), we have also developed a similar strategy for patients with recurrent GBM.