Advertisement

Topics

Study Using Vaccination With Heat Shock Protein 70 (HSP70) for the Treatment of CML in Chronic Phase

2014-08-27 03:56:28 | BioPortfolio

Summary

Description: The trial is designed to determine the response of the immune system of patients with CML to a vaccine made from their own tumor. Researchers believe that this particular vaccine, which is made from purified heat shock proteins taken from each patient's tumor, alerts the body's immune system to recognize and attack invading cancer. To be considered potentially eligible for this study you must have CML in the chronic phase.

Length/Duration: Vaccinations will be administered weekly for eight weeks. One clinic follow up visit will be scheduled two weeks after the final vaccination.

Description

Rational for immunotherapy of CML

Conceptually,CML in chronic phase is the best model for immunological intervention. It is a disease as a result of chromosomal translocation, which generates a true tumor-specific antigen. Patients in chronic phase have relatively preserved immune function for a prolonged period of time. Studies have indeed shown that peptides spanning the junctional region of both the bcr/abl and abl/bcr fusion proteins can bind to major histocompatibility complex (MHC) class I molecules (Berke et al. 2000). Vaccination of patients with bcr/abl breakpoint fusion peptides generates specific immune responses (Pinilla-Ibarz et al. 2000). In addition, for patients relapsed after bone marrow or stem cell transplant, donor lymphocyte infusion is effective in inducing a majority of them into remission. The role of donor lymphocyte infusion has proven the original concept of graft versus leukemia effect and the effectiveness of immunotherapy, in practice, towards CML (Dazzi et al. 1999). More recently, it was found that the presence of cytotoxic T lymphocytes (CTL) against HLA-A2-restricted myeloid-specific antigen proteinase 3 correlates significantly with cytogenetic remission of CML treated either with IFN or stem cell transplant (Molldrem et al. 2000), which provides strong evidence for a role of T cell immunity in clearing malignant cells.

Current proposal and hypothesis:

Based on the established roles of HSPs in T cell immunity and a large body of preclinical and clinical safety data, we propose to initiate a pilot study to test the feasibility of immunization with autologous tumor-derived HSP70 in the treatment of CML in chronic phase. This study will facilitate more clinical trials in the future, testing the ultimate hypothesis that the combination of the cytostatic therapy such as IFN and STI571, with specific immunomodulator such as HSP70 offers the best chance of eradication of CML. A total of 10 eligible patients will be enrolled in the study. All eligible patients will undergo aphaeresis to collect peripheral blood mononuclear cells. The autologous HSP70 is then purified using the standard protocol. After passing the established sterility testing, the patients are immunized intradermally with 50 micrograms HSP70 for a total of 8 injections in 2 months. They may receive their standard therapy during this time. In addition to collecting the feasibility and toxicity data, the development of anti-tumor immunity will be measured by,

1. an increase in peripheral blood of IFN-gamma producing CD8+ T-lymphocytes which are reactive to the autologous bcr/abl positive peripheral mononuclear cells

2. an increase of PR-1 specific CTLs by PR1-HLA-A2 tetramer techniques in patients who are HLA-A2 positive

3. the change of immunophenotype of peripheral lymphocytes

4. the cytogenetic remission of Philadelphia chromosome from the bone marrow

Study Design

Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

Leukemia,Myeloid, Chronic

Intervention

Heat Shock Protein 70 HSP70

Location

University of Connecticut Health Center
Farmington
Connecticut
United States
06030

Status

Completed

Source

University of Connecticut Health Center

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:56:28-0400

Clinical Trials [3569 Associated Clinical Trials listed on BioPortfolio]

Minnelide in Adult Patients With Relapsed or Refractory Acute Myeloid Leukemia

Minnelide, a water-soluble disodium salt variant of triptolide, is a diterpenoid heat shock protein 70 (HSP70) inhibitor. Studies using AML cell lines, primary patient samples, and mouse t...

Relationship Between Polymorphism of Heat Shock Protein 70 Gene and Hepatocellular Carcinoma

Polymorphisms of HSP70 and tumor necrosis factor-alpha promoter in patients with hepatocellular carcinoma, chronic liver disease and healthy controls will be measured by PCR-RFLP or direct...

Vaccination Against High Risk Breast Cancer Using Tumor Derived Heat Shock Protein 70

Description: The trial is designed to determine the response of the immune system of patients with breast cancer to a vaccine made from their own tumor. Researchers believe that this parti...

Vaccine Therapy in Treating Patients With Chronic Myelogenous Leukemia

RATIONALE: Vaccines made from a person's white blood cells may make the body build an immune response to kill cancer cells. PURPOSE: Phase I trial to study the effectiveness of vaccine th...

GP96 Heat Shock Protein-Peptide Complex Vaccine in Treating Patients With Recurrent or Progressive Glioma

RATIONALE: Vaccines made from a person's tumor cells, such as gp96 heat shock protein-peptide complex, may help the body build an effective immune response to kill tumor cells. PURP...

PubMed Articles [18592 Associated PubMed Articles listed on BioPortfolio]

Therapeutic potency of heat-shock protein-70 in the pathogenesis of colorectal cancer, current status and perspectives.

Heat-shock protein-70 (HSP70) is critical to the folding, stability and activity of several client proteins including many responsible for cancer cell proliferation, apoptosis, drug toxicity, and meta...

Reduction of Thermotolerance by Heat Shock Protein 90 Inhibitors in Murine Erythroleukemia Cells.

Cells induce heat shock proteins (HSPs) against various stress. However, murine erythroleukemia (MEL) cells do not express HSP72, a heat-inducible member of HSP70 family. So, it is of interest to exam...

Hsp70 chaperone: a master player in protein homeostasis.

Protein homeostasis (proteostasis) is an essential pillar for correct cellular function. Impairments in proteostasis are encountered both in aging and in several human disease conditions. Molecular ch...

The same but different: the role of Hsp70 in heat shock response and prion propagation.

The Hsp70 chaperone machinery is a key component of the heat-shock response and a modulator of prion propagation in yeast. A major factor in optimizing Hsp70 function is the highly coordinated activit...

Involvement of Stat3 phosphorylation in mild heat shock-induced thermotolerance.

Thermotolerance is a phenomenon in which cells become resistant to stress by prior exposure to heat shock, and its development is associated with the induction of heat shock proteins (Hsps), including...

Medical and Biotech [MESH] Definitions

A family of heat-shock proteins that contain a 70 amino-acid consensus sequence known as the J domain. The J domain of HSP40 heat shock proteins interacts with HSP70 HEAT-SHOCK PROTEINS. HSP40 heat-shock proteins play a role in regulating the ADENOSINE TRIPHOSPHATASES activity of HSP70 heat-shock proteins.

A group of eukaryotic high-molecular mass heat-shock proteins that represent a subfamily of HSP70 HEAT-SHOCK PROTEINS. Hsp110 proteins prevent protein aggregation and can maintain denatured proteins in folding-competent states.

Heat and cold stress-inducible, transcription factors that bind to inverted 5'-NGAAN-3' pentamer DNA sequences and are regulated by poly(ADP) ribosylation. They play essential roles as transcriptional activators of the HEAT-SHOCK RESPONSE by inducing expression of large classes of MOLECULAR CHAPERONES and heat-shock proteins. They also function in DNA REPAIR; transcriptional reactivation of latent HIV-1; and pre-mRNA processing and nuclear export of HSP70 HEAT-SHOCK PROTEINS during heat stress.

A constitutively expressed subfamily of the HSP70 heat-shock proteins. They preferentially bind and release hydrophobic peptides by an ATP-dependent process and are involved in post-translational PROTEIN TRANSLOCATION.

The phase of chronic myeloid leukemia following the chronic phase (LEUKEMIA, MYELOID, CHRONIC-PHASE), where there are increased systemic symptoms, worsening cytopenias, and refractory LEUKOCYTOSIS.

More From BioPortfolio on "Study Using Vaccination With Heat Shock Protein 70 (HSP70) for the Treatment of CML in Chronic Phase"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Antibodies
An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples of antigens include microorganisms (such as bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produc...

Vaccines
A vaccine is any preparation intended to produce immunity to a disease by stimulating the production of antibodies. It creates immunity but does not cause the disease. There are several differnt types of vaccine avalable; Killed microorganisms; which s...

Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe, its toxins or one ...


Searches Linking to this Trial