Results of a phase 1 study utilizing monocyte-derived dendritic cells pulsed with tumor RNA in children and young adults with brain cancer

Abstract

We conducted a phase 1 study of 9 pediatric patients with recurrent brain tumors using monocyte-derived dendritic cells pulsed with tumor RNA to produce antitumor vaccine (DCRNA) preparations. The objectives of this study included (1) establishing safety and feasibility and (2) measuring changes in general, antigen-specific, and tumor-specific immune responses after DCRNA. Dendritic cells were derived from freshly isolated monocytes after 7 days of culture with IL-4 and granulocyte-macrophage colony-stimulating factor, pulsed with autologous tumor RNA, and then cryopreserved. Patients received at least 3 vaccines, each consisting of an intravenous and an intradermal administration at biweekly intervals. The study showed that this method for producing and administering DCRNA from a single leukapheresis product was both feasible and safe in this pediatric brain tumor population. Immune function at the time of enrollment into the study was impaired in all patients tested. While humoral responses to recall antigens (diphtheria and tetanus) were intact in all patients, cellular responses to mitogen and recall antigens were below normal. Following DCRNA vaccine, 2 of 7 patients showed stable clinical disease and 1 of 7 showed a partial response. Two of 7 patients who were tested showed a tumor-specific immune response to DCRNA. This study showed that DCRNA vaccines are both safe and feasible in children with tumors of the central nervous system with a single leukapheresis.

Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA

“…14,26 Further, some trials have made use of immature DCs. 18,[27][28][29] Interestingly, responses to unloaded matured DCs were recently published in a lung cancer DC vaccine trial. 34 The mockDC-response in our melanoma trial may represent an autologous mixed lymphocyte reaction (AMLR).…”

“…The experience with tumor-RNA vaccines is also limited in other cancer forms. To date have been reported a pilot vaccination of a patient with lung cancer 26 followed by three phase I trials, in renal cancer, 27 pediatric brain cancer 28 and neuroblastoma. 29 The phase I studies all applied vaccination with immature DCs that were transfected by simple coincubation with tumor-RNA.…”

Intranasal mRNA nanoparticle vaccination induces prophylactic and therapeutic anti-tumor immunity

“…T umor vaccination employing mRNA transfected dendritic cells (DCs) has been shown to be an effective strategy for treatment of cancer [1][2][3][4][5][6] . Promising results emerging from recent clinical trials [7][8][9] supports the notion that this is a strategy that can be translated to humans and is amenable to commercialization.…”

Dendritic Cell Vaccination in Glioblastoma Patients Induces Systemic and Intracranial T-cell Responses Modulated by the Local Central Nervous System Tumor Microenvironment

“…Whereas recent reports using dendritic cells to treat brain tumors have yielded encouraging results (8,10,11,(21)(22)(23)25), there are still many practical and theoretical problems to be resolved. For instance, little is known about the best methods for loading dendritic cells with antigens, the optimal dose and route of administration, or how to identify subgroups of patients that are more likely to develop clinical responses.…”