A Safety and Feasibility Study of Active Immunotherapy in Patients With Metastatic Prostate Carcinoma Using Autologous Dendritic Cells Pulsed With Antigen Encoded in Amplified Autologous Tumor RNA

2014-08-27 03:57:18 | BioPortfolio


Purpose: This protocol proposes a safety and feasibility trial in patients with metastatic prostate cancer (stages D1-D3) investigating the induction of antitumor immunity by administration of cultured autologous peripheral blood precursor derived dendritic cells (DC), transfected with mRNA amplified from autologous prostate tumor tissue. The feasibility and dose-limiting toxicity of administering escalating doses of tumor RNA transfected dendritic cells will be defined. As a secondary endpoint, the ability of tumor RNA transfected dendritic cells to induce tumor-specific immune responses will be evaluated. Finally, the anti-tumor effect based on PSA (biochemical) response criteria will be defined.

Background: Because prostate cancer is incurable when metastatic and conventional therapies do not offer a clear survival benefit, new therapeutic strategies are warranted. This study is based on the premise that clinically effective cell mediated immune responses against prostate tumors can be elicited by activation of tumor associated antigen specific T cells. Work performed by others and our group suggests that PSA, a protein expressed in virtually all prostate cancers, can serve as a widely expressed candidate antigen for prostate cancer immunotherapy. In particular, we have shown that cultured dendritic cells transfected with mRNA encoding PSA are remarkably effective in stimulating antigen specific immunity in vitro. Therefore, we hypothesize that administration of PSA RNA transfected DC will lead to detectable levels of PSA specific CTL in the peripheral blood of patients with PSA expressing metastatic prostate cancer. It is hoped that these T cell responses also have clinical antitumor activity.


Methods: Patients will undergo percutaneous needle biopsies from either primary or metastatic sites to obtain tumor tissue. Patients in whom sufficient tumor mRNA has been amplified by PCR to transfect the assigned dendritic cell dose will undergo leukapheresis and peripheral blood mononuclear cells will be cultured in vitro for 7 days with GM-CSF and IL-4 to generate precursor derived dendritic cells. Dendritic cells will then be cryopreserved for later use. On the day the patient returns to receive his infusion (weeks 0, 2, and 4) the dendritic cells will be thawed, reconstituted, and transfected with amplified total tumor mRNA. Patients will receive a total of 3 treatments consisting of combined I.V. and I.D. injections, each on study week 0, 2, and 4. Repeat leukapheresis will be performed 2 weeks after the last dose to determine immune function. PSA levels will be measured prior to the start of treatment and 2 weeks following the last infusion. Patients who do not receive therapy due to a failure to produce sufficient RNA or dendritic cells will be replaced in order to assess toxicity.

Data Analysis: 1. To determine the short and long term toxicities associated with administration of tumor RNA dendritic cells in patients with metastatic prostate cancer. 2. To determine feasibility of dendritic cell vaccine generation according to the proportion of patients for whom sufficient cells are generated to provide treatment. 3. To determine the cellular immune response to intravenous infusion of tumor RNA dendritic cells. 4. To measure the PSA response of patients with metastatic prostate cancer to intravenous infusion of tumor RNA dendritic cells.

Study Design

Primary Purpose: Treatment


Prostate Cancer


Autologous dendritic cells transfected with amplified tumor RNA


Duke University Medical Center
North Carolina
United States


Active, not recruiting


National Center for Research Resources (NCRR)

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:57:18-0400

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Medical and Biotech [MESH] Definitions

Non-hematopoietic cells, with extensive dendritic processes, found in the primary and secondary follicles of lymphoid tissue (the B cell zones). They are different from conventional DENDRITIC CELLS associated with T-CELLS. They are derived from MESENCHYMAL STEM CELLS and are negative for class II MHC antigen and do not process or present antigen like the conventional dendritic cells do. Instead, follicular dendritic cells have FC RECEPTORS and C3B RECEPTORS that hold antigen in the form of ANTIGEN-ANTIBODY COMPLEXES on their surfaces for long periods for recognition by B-CELLS.

Recirculating, dendritic, antigen-presenting cells containing characteristic racket-shaped granules (Birbeck granules). They are found principally in the stratum spinosum of the EPIDERMIS and are rich in Class II MAJOR HISTOCOMPATIBILITY COMPLEX molecules. Langerhans cells were the first dendritic cell to be described and have been a model of study for other dendritic cells (DCs), especially other migrating DCs such as dermal DCs and INTERSTITIAL DENDRITIC CELLS.

Lymphocytes that show specificity for autologous tumor cells. Ex vivo isolation and culturing of TIL with interleukin-2, followed by reinfusion into the patient, is one form of adoptive immunotherapy of cancer.

A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer.

A tumor necrosis factor receptor family member that is specific for RANK LIGAND and plays a role in bone homeostasis by regulating osteoclastogenesis. It also expressed on DENDRITIC CELLS where is plays a role in regulating dendritic cell survival. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.

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