Vaccine plus chemotherapy prolongs survival of patients with glioblastoma

Treating patients with glioblastoma multiforme (GBM) with dendritic cell immunotherapy seems to sensitize the tumor to subsequent chemotherapy, according to a study by researchers at Cedars-Sinai Medical Center in Los Angeles.

In the study, published in the August 15 issue of Clinical Cancer Research, patients with these malignant brain tumors who were treated with both a cancer vaccine and chemotherapy survived longer and exhibited significantly delayed tumor progression compared with those treated with either treatment modality alone.”This is the strongest effect of any therapy on brain tumors we’ve seen so far,” lead investigator Dr. Christopher J. Wheeler told Reuters Health.Cancer vaccines elicit tumor-reactive cytotoxic T lymphocytes (CTL), but this tends not to translate into clinical benefit for these patients, Dr. Wheeler and his team write. They theorized that the CTL response cannot keep pace with rapidly growing, mutating tumors. They therefore examined the possibility of synergy between vaccination and conventional chemotherapy.The patients, ages 32 to 78 years old, had de novo GBM and underwent craniotomy and radiation therapy. Vaccine was derived from autologous dendritic cells loaded with cells obtained from cell cultures of resected tumor samples or cell lysates. Twelve patients were administered vaccine subcutaneously three times 2 weeks apart beginning at about week 15 after diagnosis.Thirteen patients underwent chemotherapy alone, and 13 were given both vaccine and chemotherapy.Average length of survival was 26 months in the combined treatment group, compared with 18 months for those given vaccine alone and 16 months for those undergoing chemotherapy alone.The 42% of patients in the combined treatment group surviving 2 years and the 18% surviving 3 years are quite uncommon for patients with GBM, the authors note, as are the three cases in which tumor mass regressed more than 50%.”Additional independent evidence linked levels of the predominant anti-tumor effector T cells in GBM patients and CD8+ recent thymic emigrants to chemotherapeutic responsiveness, consistent with a direct influence of anti-tumor immunity on GBM chemo sensitivity,” Dr. Wheeler and his associates write.”We also found that TREC [T cell receptor excision circle] analysis does give an indication of both vaccine efficacy and clinical efficacy in brain tumor patients,” Dr. Wheeler said in an interview with Reuters Health. In order to improve patient survival even longer, they hope that “by supplementing patients with more CD8+ cells that bear TRECs prior to vaccination we can have a greater vaccine-induced immune response,” he added. “The problem is there are not that many type of cells in a patient, so we are looking at the salient properties of those cells, trying to make other types of immune cells more like those important T cells.”Dr. Wheeler noted that his group is now in the process of “streamlining a clinical protocol” using an animal model of GBM, in preparation for starting a larger, multi-institutional trial of combined immunotherapy/chemotherapy for patients with GBM.(Source: Clin Cancer Res 2004: Reuters Health News: Reuters Health: Karla Gale: Oncolink: August 2004)