Intratumoral neoadjuvant immunotherapy using IL-12 and dendritic cells is an effective strategy to control recurrence of murine hepatocellular carcinoma in immunosuppressed mice.
نویسندگان
چکیده
Liver transplantation is accepted as an effective therapy for hepatocellular carcinoma (HCC). However, recurrence is one of the most fatal complications. The aim of this study is to evaluate the efficacy of intratumoral immunotherapy using IL-12 gene therapy and dendritic cell injection for the purpose of effective treatment for HCC under conditions of immunosuppression. We found that the combined immunotherapy significantly induced sustained and high amounts of intratumoral IL-12 and IFN-gamma proteins and that it induced high HCC-specific CTL activity under immunosuppression as compared with each monotherapy or control. The combined immunotherapy also exerted effective antitumor effects on the immunosuppressed host, resulting in significant suppression of growth of the s.c. established tumor and complete suppression of lung and liver metastasis, without rejection of a fully allogeneic skin graft. These antitumor effects were dependent on both T cells and NK cells. Noteworthily, the combined intratumoral immunotherapy and tumor resection (that is, neoadjuvant immunotherapy) resulted in achievement of tumor-free and long-term survival of the some immunosuppressed mice, even when the mice were challenged with i.v. injection of HCC at the time of tumor resection. In contrast, all of the mice treated with neoadjuvant immunotherapy using monotherapy or control therapy suffered from lung and liver metastasis. These results suggest that intratumoral neoadjuvant immunotherapy using IL-12 gene therapy and dendritic cell therapy is a potent effective strategy to control recurrence of HCC in patients after liver transplantation for HCC and may be applicable to general cancer treatment.
منابع مشابه
Murine Hepatocellular Carcinoma in Effective Strategy To Control Recurrence of Using IL-12 and Dendritic Cells Is an Intratumoral Neoadjuvant Immunotherapy
متن کامل
IL-12 gene therapy is an effective therapeutic strategy for hepatocellular carcinoma in immunosuppressed mice.
Immunosuppressive therapy for organ transplantation is essential for controlling rejection. When liver transplantation is performed as a therapy for hepatocellular carcinoma (HCC), recurrent HCC is one of the most fatal complications. In this study, we show that intratumoral murine IL-12 (mIL-12) gene therapy has the potential to be an effective treatment for malignancies under immunosuppressio...
متن کاملDendritic Cell Maturation with CpG for Tumor Immunotherapy
Background: Bacterial DNA has immunostimulatory effects on different types of immune cells such as dendritic cells (DCs). Application of DCs as a cellular adjuvant represents a promising approach in the immunotherapy of infectious disease and cancers. Objectives: To investigate the effect of tumor antigen pulsed DCs in the presence of CpG-1826 in treatment of a murine model of cancer. Methods: ...
متن کاملEffects of Dendritic Cell Vaccine Activated with Components of Lieshmania Major on Tumor Specific Response
Background: Dendritic cells (DCs) contribute essentially to the outset and course of immune responses. So in patients with malignancy, there have been considerable interests in use of these cells in different interventions. Objective: To evaluate the impact of Leishmania major’s components on DC maturation and their use as a therapeutic agent against t...
متن کاملNeoadjuvant immunotherapy with chitosan and interleukin-12 to control breast cancer metastasis
Metastasis accounts for approximately 90% of breast cancer-related deaths. Therefore, novel approaches which prevent or control breast cancer metastases are of significant clinical interest. Interleukin-12 (IL-12)-based immunotherapies have shown promise in controlling metastatic disease, yet modest responses and severe toxicities due to systemic administration of IL-12 in early trials have hin...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of immunology
دوره 185 1 شماره
صفحات -
تاریخ انتشار 2010