A Pilot Study of Vaccination With Epitope-Enhanced TARP Peptide and TARP Peptide-Pulsed Dendritic Cells in the Treatment of Stage D0 Prostate Cancer

2014-08-27 03:19:31 | BioPortfolio



- PSA (prostate specific antigen) is a protein found on normal and cancerous prostate cells. Levels of this protein are used to identify men who are at risk for prostate cancer and to monitor responses to treatment in men who have been diagnosed with prostate cancer.

- Research has shown that men who continue to have an elevated PSA level following primary treatment for prostate cancer are at increased risk for cancer progression. Studies have shown that the change in PSA levels over time, or PSA doubling time (PSADT), can be accurate in predicting how quickly the cancer is likely to progress. Individuals with a PSADT of less than 3 months are at extremely high risk for disease progression and death from prostate cancer. Individuals with a PSADT of greater than 15 months have a very low risk of death from prostate cancer.

- TARP is a protein that is found in about 95% of prostate cancers and is known to stimulate the immune system. The TARP prostate cancer vaccine is made from pieces of the TARP protein called peptides and includes peptides that have been modified to make them more effective at stimulating immunity. Although these TARP peptides have been shown to stimulate the immune systems of mice, information is needed to determine if they also stimulate the immune system in humans. Since it is unclear what is the best way to give peptide vaccines, the TARP peptides will be given with substances known to stimulate the immune system or in a vaccine made with the patient's own cells.


- To determine the immune system's response to vaccination with TARP peptides.

- To determine the safety and toxicity of TARP peptide vaccination.

- To determine if vaccination with the TARP prostate cancer vaccine can slow down PSADT in men with an intermediate PSADT of 3 to 15 months.


- Males 18 years of age and older who have completed their primary treatment for prostate cancer, have stage D0 disease, are HLA A*0201 positive and who have a PSADT greater than 3 and less than 15 months.


- Patients will be randomized to one of two treatment arms:

- Arm A will receive the TARP vaccine with other substances that stimulate the immune system.

- Arm B will receive the TARP vaccine that includes a patient's own white blood cells.

- First week of study, after screening for eligibility has been completed:

- Day 1: Apheresis procedure to extract white blood cells...



- T-cell receptor alternate reading frame protein (TARP) is expressed by both normal and malignant prostate cancer tissue and is found in about 95% of prostate cancer specimens. TARP is immunogenic and hence is a target antigen for vaccination.

- The immunogenicity of TARP peptides can be augmented through epitope enhancement that is achieved through amino acid substitutions resulting in increased peptide binding affinity.

- Two HLA-A*0201 TARP peptide epitopes are associated with generation of catalytic T-cell responses: TARP27-35 and TARP29-37. Substitution of Val for Leu at position 9 in TARP29-37, results in a peptide with increased binding affinity (TARP29-37-9V) that induces antigen specific T cells able to recognize wild type and multiple modified TARP peptides. The affinity of the TARP 27-35 peptide, corresponding to a distinct but overlapping epitope, is high enough that no enhancement was required.

- Stage D0 prostate cancer patients have no evidence of visceral or bony metastatic disease but have persistently elevated or rising PSA levels (biochemical progression) and are at increased risk for disease progression. Since they lack much of the immune dysfunction associated with the high tumor burden characteristic of end-stage metastatic disease, they are an ideal population in which to study therapeutic vaccination to slow or prevent disease recurrence and progression.

- Dendritic cells (DC) are the most potent antigen-presenting cells of the immune system and are being studied extensively for anti-tumor activity in a broad spectrum of cancer patients.

- As the optimal method for therapeutic immunization with peptide vaccines in patients with cancer is unclear, vaccination with TARP peptides in Montanide(Registered Trademark) ISA 51 VG adjuvant plus Sargramostim will be studied in a randomized fashion with autologous, TARP peptide-pulsed DCs in HLA-A*0201 Stage D0 prostate cancer patients.



- Determine the safety and toxicity of TARP peptide and TARP peptide-pulsed dendritic cell vaccination in patients with Stage D0 prostate cancer.

- Determine the T-lymphocyte immune responses to TARP peptide vaccination with Montanide(Registered Trademark) ISA 51 VG plus Sargramostim or autologous dendritic cells as measured by tetramer staining, IFN-gamma ELISPOT and (51)Cr release CTL assays.


-Determine the effect of TARP peptide vaccination on serum prostate specific antigen doubling time (PSADT) in patients with PSADT greater than 3 months and less than 15 months.


- Males greater than or equal to 18 years of age with histologically confirmed adenocarcinoma of the prostate.

- Must have completed and recovered from all prior definitive therapy (surgery, brachytherapy, cryotherapy or radiotherapy) for the primary tumor, or other definitive-intent local therapy.

- Stage D0 disease with documented biochemical progression documented by rising PSA and no evidence of metastatic disease by physical examination, CT scan or bone scan.

- PSADT > 3 months and < or equal to 15 months:

- Patients must have greater than or equal to 3 PSA measurements over greater than or equal to 3 months.

- The interval between PSA measurements must be greater than or equal to 4 weeks.

- For patients following definitive radiation therapy or cryotherapy: a rise in PSA of > 2ng/mL above the nadir.

- For patients following radical prostatectomy: 2 absolute PSA values > 0.3ng/ml.

- Non-castrate level of testosterone: greater than or equal to 50 ng/dL (prior ADT allowed; must be greater than or equal to 6 months since last dose of ADT).

- HLA-A*0201 positive.

- Performance Status: ECOG 0-2 or Karnofsky 70-100% and life expectancy greater than or equal to 1 year.

- Hemoglobin greater than or equal to 10.0 gm/dL, WBC greater than or equal to 3,000/mm(3), ALC greater than or equal to 800/ mm(3), ANC greater than or equal to 1,500/mm(3), platelet count greater than or equal to 100,000/mm(3), and PT/PTT less than or equal to 1.5 times ULN; SGPT/SGOTless than or equal to 2.5 times ULN, total bilirubin less than or equal to 1.5 times ULN; creatinine less than or equal to 1.5 times ULN and estimated GFR (eGFR) greater than or equal to 60 ml/min.

- Hepatitis B and C negative (unless the result is consistent with prior vaccination or prior infection with full recovery); HIV negative.

- No use of investigational agents within 4 weeks of study enrollment or use of immunosuppressive or immunomodulating agents within 8 weeks of study entry.

- No other concurrent anticancer therapy or prior prostate cancer vaccines expressing TARP or HLA A2.

- No alternative medications known to alter PSA (e.g. phytoestrogens and saw palmetto). Note: patients receiving medications for urinary symptoms such as Flomax or 5-alpha reductase inhibitors (finasteride and dutasteride) on a chronic stable dose for at least 3 months are allowed.


- This is a randomized, prospective, pilot study of vaccination with a mixture of wild type (TARP27-35) and epitope-enhanced (TARP29-37-9V) TARP peptides in HLA-A*0201 patients with stage D0 prostate cancer.

- Vaccination with TARP peptides admixed with Montanide(Registered Trademark) ISA 51 VG plus Sargramostim administered by deep subcutaneous injection will be compared with vaccination with TARP peptide-pulsed autologous dendritic cells (DCs) administered intradermally.

- Autologous dendritic cells will be matured from peripheral blood monocytes with Sargramostim, IL-4, IFN-gamma and LPS and pulsed with wild type and epitope-enhanced TARP peptides.

- Apheresis will be performed on all patients at weeks 0, 24 and 48.

Randomization and assignment to received TARP peptide vaccine with Montanide(Registered Trademark) ISA 51 VG plus Sargramostimgiven by deep subcutaneous injection or TARP peptide-pulsed autologous DCs given ID will be performed at week 0.

- All patients will receive live, attenuated influenza vaccine (FluMist (Trademark)) when seasonally available at the very end of their week 0 visit as a control vaccine to assess cytotoxic T lymphocyte responses.

- TARP Peptide vaccines will be administered every three weeks at weeks 3, 6, 9, 12, and 15 for a total of five vaccinations. Follow-up will be through 48 weeks on study.

- The trial uses an optimal 2-stage design targeting an immunologic response between 10 and 40%. We will initially accrue 9 patients in each arm. If 0-1 patients develop an immunologic response, then no further patients will be enrolled. If 2 or more of these patients develop an immunologic response, we will accrue 11 additional patients for a maximum total of up to 20 patients in each arm. A stopping rule for excessive toxicity will be incorporated.

Study Design

Allocation: Randomized, Control: Dose Comparison, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Prostatic Neoplasms


TARP 29-35 Peptide (Native Peptide), TARP 29-37-9V Peptide Epitope Enchanced Peptide


National Institutes of Health Clinical Center, 9000 Rockville Pike
United States




National Institutes of Health Clinical Center (CC)

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:19:31-0400

Clinical Trials [947 Associated Clinical Trials listed on BioPortfolio]

Vaccine Therapy in Treating Patients With Progressive Stage D0 Prostate Cancer

RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. It is not yet known whether vaccines are more effective with or without den...

PSMA and TARP Peptide Vaccine With Poly IC-LC Adjuvant in HLA-A2 (+) Patients With Elevated PSA After Initial Definitive Treatment

The purpose of the study is to see if the PSMA/TARP proteins in the vaccine, along with the Hiltonol, can arouse and train your immune system to kill the prostate cancer cells. Prostate ca...

Immunotherapy of Stage III/IV Melanoma Patients

The purpose of this study is to determine whether vaccination with melanoma antigen peptides [Melan-A/Mart-1 (both EAA and ELA), NY-ESO-1b analog, Long NY-ESO-1 LP and MAGE-A10] and Montan...

Phase II Study of the Efficacy of Peptide T in HIV-Positive Individuals With Cognitive Impairment.

To evaluate the chemical efficacy and safety of intranasally administered peptide T on neurocognitive function in HIV seropositive individuals. Previous studies have shown that treatment ...

Histocompatibility Leukocyte Antigen (HLA)-A*2402 Restricted Peptide Vaccine Therapy in Patients With Breast Cancer

The purpose of this study is to evaluate the safety and time to progression of HLA-A*2402 restricted epitope peptide TTK emulsified with Montanide ISA 51.

PubMed Articles [4178 Associated PubMed Articles listed on BioPortfolio]

Conformational and dynamical basis for cross-reactivity observed between anti HIV-1 protease antibody with protease and an epitope peptide from it.

F11.2.32 is a monoclonal antibody raised against HIV-1 protease and it inhibits protease activity. While the structure of the epitope peptide in complex with the antibody is known, how protease intera...

MDockPeP: An ab-initio protein-peptide docking server.

Protein-peptide interactions play a crucial role in a variety of cellular processes. The protein-peptide complex structure is a key to understand the mechanisms underlying protein-peptide interactions...

How Does Aqueous Choline-O-Sulfate Solution Nullify the Action of Urea in Protein Denaturation?

Choline-O-sulfate (COS) acts as a protecting osmolyte in several plants, fungal and bacterial species. Classical molecular dynamics simulation is performed to examine the molecular mechanism by which ...

Novel peptide inhibits inflammation by suppressing of protease activated receptor-2.

We synthesized and investigated the effects of a novel peptide B, RRFSLLRY as a novel PAR-2 antagonist. Peptide B decreased calcium levels in HaCat cells stimulated with trypsin and PAR-2 activator (S...

A new method of N to C sequential ligation using thioacid capture ligation and native chemical ligation.

Sequential peptide ligation strategy becomes more and more important in large protein or long peptides chemical synthesis due to the limited peptide/protein size obtained by solid phase synthesis of i...

Medical and Biotech [MESH] Definitions

The production of PEPTIDES or PROTEINS by the constituents of a living organism. The biosynthesis of proteins on RIBOSOMES following an RNA template is termed translation (TRANSLATION, GENETIC). There are other, non-ribosomal peptide biosynthesis (PEPTIDE BIOSYNTHESIS, NUCLEIC ACID-INDEPENDENT) mechanisms carried out by PEPTIDE SYNTHASES and PEPTIDYLTRANSFERASES. Further modifications of peptide chains yield functional peptide and protein molecules.

A 36-amino acid peptide produced by the L cells of the distal small intestine and colon. Peptide YY inhibits gastric and pancreatic secretion.

The middle segment of proinsulin that is between the N-terminal B-chain and the C-terminal A-chain. It is a pancreatic peptide of about 31 residues, depending on the species. Upon proteolytic cleavage of proinsulin, equimolar INSULIN and C-peptide are released. C-peptide immunoassay has been used to assess pancreatic beta cell function in diabetic patients with circulating insulin antibodies or exogenous insulin. Half-life of C-peptide is 30 min, almost 8 times that of insulin.

A 27-amino acid peptide with histidine at the N-terminal and isoleucine amide at the C-terminal. The exact amino acid composition of the peptide is species dependent. The peptide is secreted in the intestine, but is found in the nervous system, many organs, and in the majority of peripheral tissues. It has a wide range of biological actions, affecting the cardiovascular, gastrointestinal, respiratory, and central nervous systems.

A pituitary adenylate cyclase-activating peptide receptor subtype found in LYMPHOCYTES. It binds both PACAP and VASOACTIVE INTESTINAL PEPTIDE and regulates immune responses.

More From BioPortfolio on "A Pilot Study of Vaccination With Epitope-Enhanced TARP Peptide and TARP Peptide-Pulsed Dendritic Cells in the Treatment of Stage D0 Prostate Cancer"

Quick Search


Relevant Topics

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...

Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Searches Linking to this Trial