Tumor Stem Cell Antigens as Consolidative Active Specific Immunotherapy

Abstract

Only 10% of metastatic melanoma patients survive 5 years, even though many can achieve substantial tumor reduction by surgical resection and/or radiation therapy and/or systemic therapy. An effective, nontoxic, consolidation immunotherapy could benefit such patients. We initiated a randomized trial to compare 2 promising patient-specific immunotherapy cell products. Patients had to have a diagnosis of metastatic melanoma and availability of an autologous melanoma cell line. Patients were stratified by whether their most advanced stage had been regional or distant metastases, and by whether they had measurable disease at the time of treatment, then they were randomized to receive irradiated autologous proliferating tumor cells or autologous dendritic cells (DC) loaded with antigens from such cells. Both products were injected subcutaneously in 500 µg of granulocyte-macrophage colony stimulating factor, weekly for 3 weeks and then monthly for 5 months. Patients in the 2 arms did not differ in baseline characteristics. All patients received prescribed therapy. Treatment was well tolerated. At the time of initial analysis, with no patients lost to follow-up, 50% of patients deceased, and all surviving patients followed for at least 6 months after randomization, survival is superior in the DC arm (hazard ratio, 0.27; 95% confidence interval, 0.098-0.729) with median survival not reached versus 15.9 months, and 2-year survival rates of 72% versus 31% (P=0.007). This trial provides evidence that a DC vaccine is associated with longer survival compared with a tumor cell vaccine, and is consistent with previous data suggesting a survival benefit from this patient-specific immunotherapy.

Experimental immunology Necrosis and apoptosis in Trichinella spiralis -mediated tumour reduction

“…Although most of them are still in the phase of preclinical in vitro and in vivo models, a number of potential cancer immunotherapies have reached a phase III clinical trials in the last 25 years [29]. Dendritic cells-based vaccination with the potential to boost cancer-specific effector T cells and target CSCs, like those for glioblastoma and melanoma, are either in preclinical in vitro phase [30, 31] or in clinical phase I or II [32, 33]. The only DC-based vaccine approved by the Food and Drug Administration (FDA) is Provenge for prostate cancer treatment.…”

Current status of granulocyte–macrophage colony-stimulating factor in the immunotherapy of melanoma

“…These include an oncolytic vaccinia virus encoding GM-CSF [91], autologous dendritic cells and allogeneic whole tumor cells encoding GM-CSF [92-94], adjuvant GM-CSF following vaccination with peptide or RNA encoding melanoma peptides [95,96] and autologous dendritic cell or whole tumor cell vaccines [97], and GM-CSF DNA vaccines [98]. …”

Combinations of Radiation Therapy and Immunotherapy for Melanoma: A Review of Clinical Outcomes

“…The type of radiation may affect vaccine development as gamma-radiation (at 200 Gy) was shown to yield different immunologic effects on melanoma cells than other forms of non-ionizing radiation (32). A randomized phase II study of patients with metastatic melanoma demonstrated improvements in overall survival with autologous DCs loaded with antigens from irradiated autologous patient-specific proliferating melanoma cells, compared to irradiated autologous patient-specific proliferating tumor cells (33). Interestingly, a multivariable analysis of patients treated with the aforementioned DC therapy revealed that prior radiotherapy for melanoma was associated with improved survival (34).…”