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FBO DAILY ISSUE OF SEPTEMBER 07, 2008 FBO #2477
SOLICITATION NOTICE

65 -- Peptide Sequences

Notice Date

9/5/2008
 

Notice Type

Combined Synopsis/Solicitation
 

NAICS

325414 — Biological Product (except Diagnostic) Manufacturing
 

Contracting Office

Department of Health and Human Services, National Institutes of Health, National Heart, Lung and Blood Institute, Rockledge Dr. Bethesda, MD, Office of Acquisitions, 6701 Rockledge Dr RKL2/6100 MSC 7902, Bethesda, Maryland, 20892-7902
 

ZIP Code

20892-7902
 

Solicitation Number

NHLBI-PB-{HL}-2008-259-DDC
 

Archive Date

9/30/2008
 

Point of Contact

Deborah - Coulter,, Phone: (301) 435-0368, Chris Belt,, Phone: 301.435.6672
 

E-Mail Address

dc143b@nih.gov, cbelt@nhlbi.nih.gov
 

Small Business Set-Aside

N/A
 

Description

Solicitation Number: NHLBI-PB-(HL)-2008-259-DDC This is a combined synopsis/solicitation for commercial items prepared in accordance with the format in FAR 12.6 as supplemented with additional information included in this notice. This announcement constitutes the only solicitation and a separate written solicitation will not be issued. This solicitation number is NHLBI-PB-(HL)-2008-259-DDC and is issued as a Request for Quotation (RFQ). The solicitation/contract will include all applicable provisions and clauses in effect through Federal Acquisition Circular 2005-26. The North American Industry Classification (NAICS) Code is 325414 and the business size standard is 500 employees. This acquisition is being conducted using Simplified Acquisition Procedures in accordance with FAR Part 13. However, this solicitation is not set aside for small business. It is the intent of the National Institutes of Health (NIH) National Heart, Lung and Blood Institute to procure the services as outlined in the Statement of Work, from NeoMPS Poly Peptide Laboratories Group, 9395 Cabot Drive, San Diego, California 92126-4310. The National Heart Lung and Blood Institute (NHLBI) conducts and supports biomedical research in pursuit of knowledge to extend healthy life and reduce the burden of disease and disability. The Stem Cell Allo-Transplantation Section (SCAT), Hematology Branch (HB), within NHLBI is an international leader of biomedical research in peripheral blood stem cell transplantation (PBSCT) for leukemia. Patients of all ages (8-80) from across the United States and foreign countries come to the Clinical Center on the campus of the National Institutes of Health (NIH) in Bethesda, Maryland, to receive treatments for these fatal diseases, participating in research trials conducted by the Hematology Branch. The Branch’s SCAT section conducts clinical and laboratory investigations of the treatment and prevention of the complications of PBSCT, namely, graft-versus host disease (GVHD) and relapse as well as methods to optimize of graft-versus-leukemia (GVL). A critical part of fulfilling this mission is the ability to test the efficacy of peptide vaccines in leukemia patients after PBSCT or for patients who do not have a donor for PBSCT. The effects of the WT1 and PR1 peptide vaccines have been studied in a small group and the findings are now useful as the foundation for advanced clinical trials, in which it is hoped that the efficacy of the vaccine can be enhanced. The SCAT Section proposes to investigate a multi-epitope vaccine approach, combining HLA-A*0201 restricted epitopes derived from PR3, WT1 and PRAME. We will use this multi-epitope vaccine approach as a platform to study and manipulate the immune response and overcome tolerance to achieve a successful vaccine-induced anti-leukemia effect. Purpose: Research conducted within the Hematology Branch seeks to develop new approaches to treatment and prevention of leukemia and other blood diseases. Patients with higher than standard risk leukemia sometimes relapse after transplantation (40-60%) resulting in few options for recovery and survival. Recent phase I clinical trials of PR1 and WT1 vaccination by our group and others have been reported in patients with a variety of malignancies including leukemia, myelodysplasia and solid tumors. Immunological response to vaccination associated with reduction in leukemic blast cells or tumor sizes and/or tumor markers in a proportion of patients could be demonstrated. However vaccine-induced immunity is rapidly lost after vaccination. Most leukemia- and tumor-associated antigens are self-antigens and as such may induce tolerance. We therefore hypothesize that efficient leukemia vaccination may be achieved provided that ideal leukemia-associated antigens (LAA) are used and the optimum immunological conditions to overcome tolerance are established. We will investigate whether the immunostimulatory properties of multi-epitope vaccination can be further enhanced by disrupting regulatory pathways that suppress the activation and function of T-cell responses in patients with leukemia and MDS whose options for cure and choices for disease management are limited. Specific Laboratory Objectives - Specific Study Objectives: To find new T cell epitopes of PR3, WT1 and PRAME: We will screen peptide libraries composed of overlapping peptides with patient peripheral blood mononuclear cells (PBMC) tested for their ability to bind to 8 different HLA class I molecules (HLA-A*0201, HLA-A*0101, HLA-A*0301, HLA-A*1101, HLA-A*2402, HLA-B*0702, HLA-B*0801 and HLA-B*1501) using the high throughput technology iTopiaTM. The alleles are chosen to provide broad population coverage (>90%). This will allow us to offer vaccination to patients with many common HLA types other than HLA A*0201. We will use flow cytometry and intracellular cytokine assay to study the cytokine profile of CD4+ T cell responses against pools of peptides loaded onto PBMCs. This will enable us to discover new MHC class II epitopes to induce CD4 T cell responses to provide helper support to cytotoxic CTLs. To study the immune function in the immunotherapy trial: Antigen-specific T-cells are capable of a multitude of functions, including ytolysis and production of several cytokines and chemokines. Therefore measurement of only one or two T-cell functions may not provide an adequate measure of the vaccine-induced T-cell response. To determine the quality of vaccine-induced T-cell response we plan to use multi-parameter flow cytometry to assess the following T-cell functions: a) determining the cytokine profile of antigen-specific CD8+ T-cells (e.g. IL-2, IFN-γ, TNF-α, IL-4, IL-10), b) degranulation (CD107a mobilization, a marker of cytotoxicity) following stimulation with peptide and leukemia cells. c) characterization of the maturational phenotype of antigen-specific T-cells using surface antibodies directed against CD27, CD45RO, CD57 and CCR7. d) examining surface expression of PD-1, a critical marker of T-cell exhaustion, on antigen-specific CD8(+) T cells and its possible involvement in regulation of cytokine production, proliferation and survival of these cells e) defining the avidity of the response by measuring the cytokine response of CD8+ T cells to the stimulation provided by different peptide concentrations. f) correlating the vaccine-induced T-cell responses with disease response by using real-time PCR for WT1 and PRAME gene expression as markers of minimal residual disease. Specific Clinical Objectives: Up to 20 HLA-A*0201 positive patients with high risk MDS, high risk AML, high risk ALL or advanced phase CML (failed tyrosine kinase inhibitors), and no circulating blasts and unsuitable for stem cell transplant will be enrolled. This study requires the purchase of 1G each of clinical grade (GMP) peptides. We will use the recombinant IL-2 diphtheria toxin conjugate DAB389IL-2 (also known as denileukin diftitox and ONTAK, Seragen/Ligand Pharmaceuticals, San Diego, USA) to eliminate CD25-expressing Tregs prior to vaccination and enhance the vaccine-induced T-cell response. Because activated T-cells also upregulate their surface expression of CD25 following activation, ONTAK may also mediate the deletion of these cell populations thereby affecting the effector immune response against vaccines. Murine studies have shown that the timing of ONTAK administration when combined with vaccination is very important in allowing selective depletion of Tregs. Similarly, in patients with renal cell carcinoma and melanoma, treatment with ONTAK 1-4 days prior to tumor antigen vaccination resulted in enhanced effector T-cell responses. Based on these studies patients will receive a single dose of ONTAK (18 µg/kg) followed 1 day later with the multi-epitope vaccine, consisting of a combination of PRAME 100, PRAME 300, PR1, WT1-126 and WT187 peptide vaccines mixed in Montanide ISA-51 VG. This dose level of ONTAK has been shown to have optimal clinical efficacy and acceptable toxicity profiles. Patients will receive 6 doses of vaccine at bi-weekly intervals and will be monitored every 2 weeks for safety and ability to induce vaccine-specific CD8+ T cell responses. The decision to discontinue therapy for each patient will be based on the observation of grade ≥3 toxicity. The endpoints, assessed at 16 weeks will be the change in PR1, WT1 and PRAME specific T cell frequencies, WT1 and PRAME gene expression in blood and marrow, and hematological response. Decision to continue vaccination will depend on presence or absence of a disease response and antigen specific T cell responses with a bias to continue treatment in the face of responses. Contract Tasks to be performed: The contractor shall provide 1 gm each of 4 GMP peptides. The contractor shall provide the following services: Manufacture and Delivery of the following peptides: (1) GMP grade peptide WT1(122-140) 1 gram, Sequence: H-SGGQ ARMF PNAP YLPS CLES-OH, 1 750 mg vial, 1 250 mg vial, (2) GMP grade peptide PR1(163-181) 1 gram, Sequence: H-HDPP AQVL QELN VTVV TFF-OH, 1 750 mg vial, 1 250 mg vial, (3) GMP grade peptide PR7V1 gram, Sequence: H-YDAE NKLN DVLL IQLS SPANL-OH, 1 750 mg vial, 1 250 mg vial, (4) GMP grade peptide PR7I 1 gram, Sequence: H-YDAE NKLN DILL IQLS SPANL-OH, 1 750 mg vial, 1 250 mg vial, (5) Standards: QC testing: MS for Identity, AAA for Identity, RP-HPLC for Purity ≥ 95% (Excluding cysteine dimerization and methionine oxidation as applicable) Quantification of Counter Ion Acetate, Quantitative AAA for peptide content, Karl Fischer for Water Content, Residual Solvents, Total Fluorine, Bacterial Endotoxin, LAL, Bioburden. Peptides will be manufactured using protected amino acids of non-animal origin. Period of performance is expected to be 14-16 weeks, to be confirmed at time of order. The offeror must include a completed copy of the following provisions: 1) FAR Clause 52.212-1 Instructions to Offerors Commercial; 2) FAR Clause 52.212-2, Evaluation Commercial Items. As stated in FAR Clause 52.212-2 (a), The Government will award a contract resulting from this solicitation to the responsible offeror whose offer conforming to the solicitation will be most advantageous to the Government, price and other factors considered. The following factors shall be used to evaluate offers: Technical Evaluation and Price. 3) FAR Clause 52.212-3, Offeror Representations and Certifications Commercial Items; 4) FAR Clause 52.212-4, Contract Terms and Conditions Required To Implement Statues or Executive Orders Commercial Items, Contract Terms and Conditions Commercial Items; and 5) FAR Clause 52.212-5, Contract Terms and Conditions Required to Implement Statutes or Executive Orders Commercial Items Deviation for Simplified Acquisitions. This action is under the authority of 41 U.S.C. 253(c)(1), as set forth in FAR 6.302-1 and HHSAR 306-302-1. Only one responsible source and no other supplies or services will satisfy agency requirement. Interested parties may identify their interest and capability to respond to the requirement or submit proposals. This notice of intent is not a request for competitive quotations however; all responses received within 10 days from the date of publication of this synopsis will be considered by the Government. A determination by the Government not to compete this proposed acquisition is based upon responses to this notice and is solely for the purpose of determining whether to conduct a competitive acquisition. The offeror must include in their quotation, the unit price, the list price, shipping and handling costs, the delivery period after contract award, the prompt payment discount terms, the F.O.B. Point (Destination or Origin), the Dun & Bradstreet Number (DUNS), the Taxpayer Identification Number (TIN), and the certification of business size. Note: In order to receive an award from the NHLBI contractors must have a valid registration in the Central Contractor Registration (CCR) www.ccr.gov. The clauses are available in full text at http://www.arnet.gov/far. Interested vendors capable of furnishing the government with the item specified in this synopsis should submit their quotation to the below address. Quotations will be due (10) calendar days from the publication date of this synopsis or by September 24, 2008, 8:00am, Eastern Standard Time. The quotation must reference Solicitation number NHLBI-PB-(HL)-2008-259-DDC. All responsible sources may submit a quotation, which if timely received, shall be considered by the agency. Quotations must be submitted in writing to the National Heart, Lung and Blood Institute 6701 Rockledge Blvd., Room Suite 6100, Bethesda, Maryland 20892, Attention: Deborah Coulter. Faxed copies will not be accepted. Emails will be accepted. Contracting Office Address: National Institutes of Health, National Heart, Lung and Blood Institute, 6701 Rockledge Blvd. Suite 6100, Bethesda, MD 20892Point of Contact: Deborah Coulter.
 

Web Link

FedBizOpps Complete View
(https://www.fbo.gov/?s=opportunity&mode=form&id=5296eef7c934c326d91134f9f203c8d2&tab=core&_cview=1)
 

Place of Performance

Address: Building 10-CRC Room 3/5330 NIH, Bethesda, Maryland, 20892, United States

Zip Code: 20892
 

Record

SN01661055-W 20080907/080905221913-5296eef7c934c326d91134f9f203c8d2 (fbodaily.com)
 

Source

FedBizOpps Link to This Notice
(may not be valid after Archive Date)

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