Advertisement

Topics

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

Summary

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.

Description

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

Conditions

Prostate Cancer

Intervention

Autologous dendritic cells transfected with amplified tumor RNA

Location

Duke University Medical Center
Durham
North Carolina
United States
27710

Status

Active, not recruiting

Source

National Center for Research Resources (NCRR)

Results (where available)

View Results

Links

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

Clinical Trials [6623 Associated Clinical Trials listed on BioPortfolio]

Tumor RNA Transfected Dendritic Cell Vaccines

The purpose of this study is to use dendritic cells transfected with amplified RNA from autologous tumor cells to develop a vaccine strategy for the treatment of prostate cancer in patient...

Active Immunization of Patients With Carcinoma of Oral Cavity or Oropharynx With Autologous Dendritic Cells Transfected With DNA From Autologous Tumor

The primary goal of this study is to determine if the vaccine can be safely given to subjects, and to see what side effects occur (both good and bad) when they are given this experimental ...

Immunotherapy of Melanoma With Tumor Antigen RNA and Small Inhibitory RNA Transfected Autologous Dendritic Cells

Transfection with siRNA targeting the immunoproteasome alters proteasome-mediated antigen processing by the dendritic cell, generating TAA-derived peptides that we hypothesize, based on pr...

Active Immunotherapy Of Metastatic Renal Cell Carcinoma Using Autologous Dendritic Cells Transfected With Autologous Total Tumor RNA

The feasibility and dose-limiting toxicity of administering escalating doses of dendritic cells transfected with autologous renal cell carcinoma RNA DC(DCRCC-RNA) will be defined. As a sec...

Dendritic Cell Immunotherapy Against Cancer Stem Cells in Glioblastoma Patients Receiving Standard Therapy

Open, randomized study of a trivalent dendritic cell therapy compared to standard therapy in primary treated patients with IDH wild-type, MGMT-promotor methylated glioblastoma. The IMP is ...

PubMed Articles [20829 Associated PubMed Articles listed on BioPortfolio]

Cytotoxic activity of effector T cells against cholangiocarcinoma is enhanced by self-differentiated monocyte-derived dendritic cells.

Cholangiocarcinoma (CCA) is a cancer of the bile ducts that is associated with poor prognosis and poor treatment outcome. Approximately one-third of CCA patients can undergo surgery, but the recurrenc...

CD11c MHCII GM-CSF-bone marrow-derived dendritic cells act as antigen donor cells and as antigen presenting cells in neoepitope-elicited tumor immunity against a mouse fibrosarcoma.

Dendritic cells play a critical role in initiating T-cell responses. In spite of this recognition, they have not been used widely as adjuvants, nor is the mechanism of their adjuvanticity fully unders...

Administration of Interleukin-35-Conditioned Autologous Tolerogenic Dendritic Cells Prolong Allograft Survival After Heart Transplantation.

IL-35, a powerful suppressor of inflammation and autoimmunity, is primarily secreted by regulatory T cells (Tregs) and can, in turn, promote Treg differentiation. However, the precise effect of IL-35 ...

Tumor-associated myeloid cells promote tumorigenesis of non-tumorigenic human and murine prostatic epithelial cell lines.

The etiology of prostate cancer is poorly understood, but it is a multi-step process that has been linked to environmental factors that induce inflammation within the gland. Glands of prostate cancer ...

Paraneoplastic Pemphigus as a First Manifestation of an Intra-Abdominal Follicular Dendritic Cell Sarcoma: Rare Case and Review of the Literature.

Follicular dendritic cell sarcoma (FDCS) is an extremely rare malignant tumor caused by proliferation of antigen-presenting follicular dendritic cells. The tumor most commonly arises in lymph nodes, w...

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 CC-type chemokine highly expressed in the lungs, lymph nodes, placenta, and bone marrow; it is also expressed by DENDRITIC CELLS in the GERMINAL CENTER, and peripheral blood MACROPHAGES. It functions as a chemotactic factor that specifically attracts LYMPHOCYTES, especially B-Cells, into lymph node follicles, and naive T-cells towards dendritic cells and activated T-cells. It does not attract MONOCYTES or GRANULOCYTES.

More From BioPortfolio on "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"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Cancer
  Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...

Immunology
Allergies Automimmune Disease Human Papillomavirus (HPV) Immunology Vaccine Immunology is the study of immunity and the defence mechanisms of the body. A greater understanding of immunology is needed to develop vaccines, understand ...


Searches Linking to this Trial