Surgery and adjuvant dendritic cell-based tumour vaccination for patients with relapsed malignant glioma, a feasibility study

Abstract

Patients with relapsed malignant glioma have a poor prognosis. We developed a strategy of vaccination using autologous mature dendritic cells loaded with autologous tumour homogenate. In total, 12 patients with a median age of 36 years (range: 11 -78) were treated. All had relapsing malignant glioma. After surgery, vaccines were given at weeks 1 and 3, and later every 4 weeks. A median of 5 (range: 2 -7) vaccines was given. There were no serious adverse events except in one patient with gross residual tumour prior to vaccination, who repetitively developed vaccine-related peritumoral oedema. Minor toxicities were recorded in four out of 12 patients. In six patients with postoperative residual tumour, vaccination induced one stable disease during 8 weeks, and one partial response. Two of six patients with complete resection are in CCR for 3 years. Tumour vaccination for patients with relapsed malignant glioma is feasible and likely beneficial for patients with minimal residual tumour burden.

Clinical Evaluation of Dendritic Cell Vaccination for Patients with Recurrent Glioma: Results of a Clinical Phase I/II Trial

“…There have been three reports using tumor-lysate pulsed dendritic cells for patients with recurrent gliomas (6,7,25). There were no serious adverse effects and no clinical or radiological evidence of autoimmune reactions in any of the patients in these studies except one patient who repetitively developed peritumoral edema (25). Although there is some probability of shared antigens between tumor and normal central nervous system tissues, and possible contamination of normal tissue in the tumor lysate, no autoimmunity was experienced in vivo.…”

“…Furthermore, in our in vitro study, dendritic cells pulsed with a normal brain lysate failed to induce cytolytic T-cell activity against autologous glioma cells, suggesting the lack of an autoimmune response (28). The source of the dendritic cells in these cases was immature dendritic cells (6,7) and mature dendritic cells (25). The administration route was intradermal injection (7,25), and both intradermal and intratumoral injections (6).…”

“…The advantages of vaccinating with total tumor-derived material, such as tumor cell lysates or tumor-derived mRNA, are that the identities of tumor antigens need not be known and that the use of multiple tumor antigens reduces the risk of antigen-negative escape mutants. There have been three reports using tumor-lysate pulsed dendritic cells for patients with recurrent gliomas (6,7,25). There were no serious adverse effects and no clinical or radiological evidence of autoimmune reactions in any of the patients in these studies except one patient who repetitively developed peritumoral edema (25).…”

“…The source of the dendritic cells in these cases was immature dendritic cells (6,7) and mature dendritic cells (25). The administration route was intradermal injection (7,25), and both intradermal and intratumoral injections (6). Dendritic cell vaccination elicited systemic cytotoxicity detected by IFN-g expression in response to tumor lysate, and intratumoral cytotoxic T-cell infiltration was detected in several patients, although analysis of the function of these infiltrating cells should be carried out more precisely (6,7,25).…”

“…There is an increasing number of reports regarding preclinical studies (13 -18) and clinical studies (5 -7, 19) demonstrating that systemic immunotherapy using dendritic cells is capable of inducing an antitumor response within the immunologically privileged brain, confirming that the central nervous system may not be an absolute barrier to dendritic cell -based immunotherapy. Early clinical studies with immunotherapy using tumor lysate pulsed dendritic cells suggest that this could be a promising strategy for patients with cancer (20 -24) and malignant gliomas (6,7,25). In a previous report (6), we have described the vaccination of 10 malignant glioma patients with dendritic cells pulsed by an autologous tumor lysate.…”