Development of an Effective Method for Dendritic Cell Immunotherapy of Mouse Melanoma

Abstract

Dendritic cell (DC) immunotherapy is a strong candidate for the treatment of incurable cancers especially malignant melanoma. Nevertheless, the proper guideline of DC immunotherapy does not exist. The absence of the guideline is also an obstacle to clinical trials of DC immunotherapy. So we conducted this study in order to develop an effective DC preparation method for immunotherapy in mouse malignant melanoma. Mouse bone marrow‐derived DC were stimulated with tumour antigen alone or tumour antigen plus a cocktail (anti‐CD40 antibody +TNF‐α+ IL‐1β) for 8, 24 or 48 h and the characteristics of these DC, such as surface molecules (CD40, CD80, CD86, MHC class II, CCR7), cytokines(IL‐12, IFN‐γ, and IL‐10), DC‐induced T cell proliferation in vitro, and the production of IFN‐γ by those cells, were evaluated. Mice with melanoma were then treated with DC stimulated with tumour antigen alone and tumour antigen plus cocktail for 8 or 48 h. The tumour size and survival rate of these mice were then evaluated. (1) Beneficial clinical effects such as a reduction of tumour size and an increased survival rate were best observed in the group treated with DC stimulated for 8 h with tumour antigen plus cocktail. (2) The single prominent characteristic of DC stimulated for 8 h with tumour antigen plus cocktail was an elevated IL‐12 secretion. The cytokine IL‐12 was not secreted by other DC. Consequently, proper production of IL‐12 was found to be an important requirement for DC used in immunotherapy of mouse melanoma.

Metronomic Doses of Temozolomide Enhance the Efficacy of Carbon Nanotube CpG Immunotherapy in an Invasive Glioma Model

“…with SWCNT/CpG-2. Mice were sacrificed 48 hours post-treatment and splenocytes were harvested and co-incubated with irradiated (30,000 rad) K-Luc cells for 7 days [ 26 ]. Effectors were then co-incubated for 4 hours with 5,000 51 Cr-loaded K-Luc targets in 96-well plates at ratios of 100:1, 20:1, and 4:1 (nine replicates).…”

Immunotherapy of Malignant Melanoma with Tumor Lysate-Pulsed Autologous Monocyte-Derived Dendritic Cells

“…There are many factors other than Tregs depletion to be evaluated and determined in each step of DC-based vaccination in order to standardize and optimize this vaccination treatment 18. Other factors include the source of DC, maturation status of DC, maturation of cocktails, type of antigen, helper antigens, routes of administration, frequency of injections and numbers of injected DCs.…”

Reduction of major histocompatibility complex class I expression on bladder carcinoma following tumor antigen‐pulsed dendritic cell vaccine: Implications for immunoresistance in therapy

“…MHC‐I molecules are glycoproteins expressed ubiquitously by most nucleated cells and have been necessary for the presentation of antigens manufactured by these cells to naive CD8 + T lymphocytes (CTL). The published studies in animal models and human clinical trials have confirmed a positive immune response in some tumors, such as renal cancer, melanoma and breast cancer, with DC‐based vaccination strategies 7–12 . But it is still poorly known the relationship between MHC expression alteration and DC‐based vaccine during the therapy process.…”

“…The published studies in animal models and human clinical trials have confirmed a positive immune response in some tumors, such as renal cancer, melanoma and breast cancer, with DC-based vaccination strategies. [7][8][9][10][11][12] But it is still poorly known the relationship between MHC expression alteration and DC-based vaccine during the therapy process. In theory, this is of considerable importance to predict DC vaccine efficacy on treatment.…”