Glioblastoma (GBM), a devastating primary brain cancer, remains a formidable challenge with a median survival of less than 15 months despite current standard treatments of surgery, radiation, and chemotherapy. While these approaches offer limited benefits, the inevitable recurrence of tumors demands a quest for novel and effective therapies.
In this pursuit, immunotherapy using dendritic cells (DCs) has emerged as a promising strategy to bolster the body’s own defenses against GBM. DCs, recognized as the “professional” antigen processing and presenting cells, hold a crucial role in initiating anti-tumor immune responses. Researchers are now exploring the potential of harnessing DCs to enhance the body’s natural ability to fight off cancer.
Encouraging preclinical studies in GBM have demonstrated long-term tumor survival and immunological memory in mouse models through stimulating DC activity with diverse antigens and costimulatory molecules. This exciting avenue of research offers hope and optimism for the development of targeted and lasting treatments to combat this relentless disease. As we continue to delve into the potential of dendritic cell immunotherapy, a brighter future may be within reach for GBM patients and their loved ones.
Glioblastoma (GBM) is the most common and fatal primary central nervous system malignancy in adults with a median survival of less than 15 months. Surgery, radiation, and chemotherapy are the standard of care and provide modest benefits in survival, but tumor recurrence is inevitable. The poor prognosis of GBM has made the development of novel therapies targeting GBM of paramount importance. Immunotherapy via dendritic cells (DCs) has garnered attention and research as a potential strategy to boost anti-tumor immunity in recent years. As the “professional” antigen processing and presenting cells, DCs play a key role in the initiation of anti-tumor immune responses. Pre-clinical studies in GBM have shown long-term tumor survival and immunological memory in murine models with stimulation of DC activity with various antigens and
costimulatory molecules.
De Vleesvchouwer et al. and Wheeler et al. conducted large phase II trials with 56 GBM and 23 GBM patients, respectively. In De Vleesvchouwer’s study, patients >3 years of age were enrolled into a prospective cohort comparison trial (HGG-IMMUNO) in which recurrent GBM patients were treated with DCVs pulsed with autologous tumor cells in three cohorts, where each cohort served as historical control for the next cohorts. In cohort A, DCV was given at week 1 and 3 and then every 4 weeks. In cohort B, five DC vaccinations were given at 2-week intervals and then every 4 weeks. In cohort C, 4 weekly DC vaccinations were given with boosters of intradermal injections of tumor lysate. The authors found a trend for improved PFS and OS in patients younger than age 35. A subgroup analysis of patients greater than age 21 showed an improved PFS and OS in cohort C, patients treated with weekly vaccination administrations and boosters. Wheeler et al. studied the efficacy of tumor lysate pulsed DCV administered subcutaneously in 33 GBM patients, 23 recurrent and 11 newly diagnosed, at 2-week intervals for three doses and a fourth vaccination 6 weeks after the third. One patient developed metastatic GBM around the site of the vaccine injection and was thought to be due to the growth of rare radiation-resistant tumor cells present in this particular patient and not from metastasis from the original primary tumor. PFS and OS in vaccinated individuals compared favorably with patients who did not undergo DCV treatment at the trial institution during the time of the trial. Seventeen out of 34 GBM patients exhibited a positive vaccine response with seven exhibiting >1.5-fold increase in IFN-γ production before vaccination, which is suggestive of endogenous anti-tumor response. They found that the median survival in vaccine responders was 642 days compared to 430 days in vaccine non-responders. PFS was 308 days in vaccine responders compared to 167 days in vaccine non-responders.
Preclinical and clinical studies have demonstrated measurable immunological response and variably prolonged survival rates. Various combinations of synergistic adjuvants aimed at overcoming the diverse glioma-induced immunosuppression have shown promise. The interim report from the first Phase III trial of DCV in newly diagnosed GBM confirms safety and feasibility and suggests longer than expected survival with DCV. While we eagerly await the final results from the study and results from other Phase III studies, there is need to further explore the optimal combination of immune-based therapies, ideal integration of these therapies into the current standard of care, and responder phenotypes to identify patients who are most likely to benefit from the therapy.
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