Pilot immunotherapy trial in high-risk pediatric sarcomas.
ABSTRACT
Background: The prognosis for children and young adults with metastatic pediatric sarcomas remains poor. While many of these patients can achieve a complete response with intensive therapy, greater than 70% will have disease relapse within 5 years. This pilot study investigated the feasibility and safety of administering immunotherapy with immune reconstitution and dendritic cell-based autologous tumor vaccines in high-risk patients with metastatic or recurrent pediatric sarcomas.
Methods: Six patients with recurrent or metastatic Ewing sarcoma family of tumors (ESFT) underwent a tumor biopsy and leukapheresis for collection of peripheral blood mononuclear cells prior to the initiation of standard therapy. Following cytoreductive therapy, patients received an autologous lymphocyte infusion depleted of regulatory T cells plus six vaccines of monocyte-derived dendritic cells pulsed with tumor lysate and keyhole limpet hemocyanin (KLH). The primary endpoints were feasibility, identification of immune responses, and evaluation of toxicity. Secondary endpoints included determination of event free/overall survival and assessment of regulatory T cell reconstitution.
Results: Six patients with ESFT, age range 8–28 years (median age =15 years), were enrolled. Sufficient tumor samples were obtained from five patients. One patient with a recurrence in bone had enough tumor harvested to receive only three vaccinations. Each patient received an autologous T-cell infusion with a median pre and post depletion percentage of CD25+ T cells of 9.66 and 0.05 respectively. One patient had a positive immune response to tumor lysate and all six patients had a positive KLH response as measured by interferon (IFN) gamma Elispot assay. Five patients remain with no evidence of disease at 2.5– 3.5 years (median follow up = 3.15 years). One patient relapsed. All six patients are alive at time of analysis. Toxicity was minimal.
Conclusions: Analysis of this completed cohort reveals that immunotherapy is a feasible and safe adjunct to standard multimodal therapy in high-risk patients with metastatic or recurrent pediatric sarcomas. A second cohort of patients is receiving recombinant interleukin (IL)-7 to test if the efficacy of the immunotherapy can be enhanced.