The procurement of services to complete cytokine measurements in human serum samples.

1.0 DESCRIPTION The Department of Health and Human Services (HHS), National Institutes of Health (NIH), National Cancer Institute, Division of Cancer Epidemiology and Genetics (DCEG) /Clinical Genetics Branch (CGB), plans to procure, on a sole source basis, services to complete cytokine measurements in human serum samples from Eve Technologies, 3415 A3 Avenue, NW, Calgary, AB T2N 0M4, Canada. The response close date of the notice for this requirement is in accordance with FAR 5.203(b). This acquisition will be processed under FAR Part 12 - Acquisition for Commercial Items and will be made pursuant to the authority in FAR Part 13.106-1(b)(1)(i); and is exempt from the requirements of FAR Part 6. The North American Industry Classification System code is 541380 and the small business size standard is $19 million. It has been determined there are no opportunities to acquire green products or services for this procurement. 2.0 BACKGROUND The U.S. Department of Health and Human Services (HHS), National Institutes of Health (NIH), National Cancer Institute (NCI), Division of Cancer Epidemiology and Genetics (DCEG)/Clinical Genetics Branch (CGB) has collected longitudinal cohort biospecimens, including blood and serum, from individuals with telomere biology disorders. Dyskeratosis congenita related telomere biology disorders (DC/TBDs) are highly cancer-prone syndromes characterized by very short telomeres due to pathogenic germline variants in telomere biology genes. Patients with DC/TBDs are at significantly elevated risk of multiple, life-threatening medical conditions including bone marrow failure, pulmonary fibrosis, and cancer. CGB's 15-year cohort study found the risk of cancer in DC/TBDs to be ~4-fold higher than that of the general population. Notably, the risks of tongue squamous cell carcinoma and myelodysplastic syndrome were >200-fold and >500-fold greater than the general population, respectively. CGB has previously reported that critically short telomeres drive the activities of deoxyribonucleic acid (DNA) repair enzymes known to consume the metabolite, nicotinamide adenine dinucleotide (NAD). Primary fibroblasts from DC/TBD patients and late generation telomerase knockout mice display lower NAD levels and an imbalance in the NAD metabolome. This includes elevated cluster of differentiated 38 (CD38), and reduced poly (adenosine diphosphate-ribose) polymerase and silent mating type information regulation 2 homolog 1 (sirtuin1) activities. Supplementation with the NAD precursor, nicotinamide riboside (NR), or decreased NADase activity through CD38 inhibition, improved NAD homeostasis and alleviated telomere damage, defective mitochondrial biosynthesis and clearance, growth retardation, and cellular senescence of DC/TBD fibroblasts. We also observed senescence-associated cytokines, notably interleukin 6 and 8 (IL-6 and IL-8), were reduced by nicotinamide riboside treatment of DC patient fibroblasts, suggesting that cellular senescence due to NAD dysregulation was reversed. Overall, our data support restoration of NAD metabolism and reversal of cellular senescence ameliorates the biologic consequences of very short telomeres in patients with DC/TBDs. However, the baseline cytokine levels in individuals with DC/TBDs remain unknown and how these cytokines may serve as a therapeutic target in telomere biology disorders is unexplored. 3.0 SCOPE This contractor shall complete the cytokine analyses and provide measurements for the following cytokines: sCD40L (soluble CD40 ligand), EGF (epidermal growth factor), Eotaxin, FGF-2 (fibroblast growth factor-2), Flt-3 ligand (FMS related receptor tyrosine kinase 3), Fractalkine, G-CSF (granulocyte colony stimulating factor), GM-CSF (granulocyte-macrophage colony stimulating factor), GRO?, IFN?2 (interferon alpha2, IFN? (interferon gamma), IL-1? (interleukin 1 alpha), IL-1? (interleukin 1 beta), IL-1ra (interleukin 1 ra), IL-2 (interleukin 2), IL-3 (interleukin 3), IL-4 (interleukin 4), IL-5 (interleukin 5), IL-6 (interleukin 6), IL-7 (interleukin 7), IL-8 (interleukin 8), IL-9 (interleukin 9), IL-10 (interleukin 10), IL-12p40 (interleukin 12 p40), IL-12p70 (interleukin 12 p70), IL-13 (interleukin 13), IL-15 (interleukin 15), IL-17A (interleukin 17A), IL-17E/IL-25 (interleukin 17E/interleukin 25), IL-17F (interleukin 17F), IL-18 (interleukin 18), IL-22 (interleukin 22), IL-27 (interleukin 27), IP-10 (interferon gamma-induced protein 10), MCP-1 (monocyte chemoattractant protein 1), MCP-3 (monocyte chemoattractant protein 3), M-CSF (macrophage colony stimulating factor), MDC (CCL22/macrophage derived chemokine), MIG (monokine induced by gamma interferon), MIP-1? (macrophage inflammatory protein 1 alpha), MIP-1? (macrophage inflammatory protein 1 beta), PDGF-AA (platelet derived growth factor AA), PDGF-AB/BB (platelet derived growth factor-AB/BB), RANTES (Regulated upon Actviated, Normal T cell expressed and presumably secreted), TGF? (transforming growth factor alpha), TNF? (tumor necrosis factor alpha), TNF? (tumor necrosis factor beta), VEGF-A (vascular endothelian growth factor alpha). The cytokines selected are consistent with previous studies completed in DC and TBD. Data from these samples shall be returned to CGB via Excel or other electronic, fully editable and searchable format. 4.0 CONTRACT REQUIREMENTS The contractor shall perform the following tasks: Samples shall be provided to the contractor via labelled tubes without any personally identifiable information (PII). Note, samples shall be provided to the contractor via de-identified labeled tubes. No Personally Identifiable Information (PII) or Personal Health Information (PHI) shall be provided under this contract. Samples will be shipped in dry ice via overnight delivery. Samples shall be prepared, aliquoted, and provided to contractor using the minimum required volume to complete the analysis. This volume shall not exceed 100 microliters, with each sample being run in duplicate. Any residual volume remaining shall be discarded. Samples shall be provided in screw-cap cryovials with barcoded labels. Once samples are received at contractor laboratory, contractor will complete cytokine analysis using industry standard operating procedures. All samples provided by CGB shall be run using the same cytokine assay and sample handling techniques. Contractor shall complete any internal standard controls to ensure data integrity. Send CGB final cytokine datasets once sample analyses are completed. 5.0 TYPE OF ORDER This purchase order is a firm fixed price. 6.0 NON-SEVERABLE SERVICES The services specified in each contract line item (CLIN) have been determined to be non-severable services - a specific undertaking or entire job with a defined end product of value to the Government. 7.0 PERIOD OF PERFORMANCE The proposed period of performance shall be March 15, 2023 to August 14, 2023. 8.0 PLACE OF PERFORMANCE Services shall be performed onsite at the contractor's facility. 9.0 REPORT(S)/DELIVERABLES AND DELIVERY SCHEDULE The TPOC shall review the contents of all draft deliverables. If no comments or requests for revisions are provided to the Contractor within 30 business days, the deliverables shall be considered acceptable. If revisions are required, NCI shall respond to the Contractor within five (5) business days of receiving the deliverable, specifying the required changes/revisions. Final copies of approved drafts shall be delivered to the NCI TPOC within five (5) business days after receipt of the Government's comments. All deliverables shall be provided electronically (Microsoft Word or Excel compatible format, unless approved by the NCI Technical Point of Contact (TPOC) per the following deliverable schedule: DELIVERABLE: Cytokine dataset DELIVERABLE DESCRIPTION / FORMAT REQUIREMENTS: Dataset in electronic copy easily editable and searchable (ie, Excel). DUE DATE: 30 business days prior to the purchase order expiration date 10.0 UNIQUE QUALIFICATIONS OF THE CONTRACTOR Eve Technologies is a world leader in acquiring and analyzing cytokine levels in human samples. NIH has utilized their services previously with outstanding results and service. The nature of this research requires expertise in cytokine sample acquisition and handling of human samples, both of which Eve Technologies is uniquely qualified to do. The collaboration for the telomere biology disorders spans across institutes at NIH. The goal is to translate this clinical data into the lab and vice versa. The previous cytokine data in the telomere biology disorders project has been obtained at Eve Technologies and thus, the goal is to now replicate this data in primary human samples. The only way to limit variability across assays is to complete the same assays in the primary human biospecimens as what was done from patient fibroblasts in the lab, is to use the same assay at the same company. Thus, we are using Eve Technologies to maintain study design and consistency. 11.0 SUBMISSION INSTRUCTIONS This notice is not a request for competitive quotations. However, if any interested party believes it can meet the above requirements, it may submit a proposal or quote for the Government to consider. The response and any other information furnished must be in writing and must contain material in sufficient detail to allow NCI to determine if the party can perform the requirement. All responses and questions must be sent via email to the Contract Specialist, Holly Knott, at holly.knott@nih.gov by no later than 5:00 PM EST on March 8, 2023. A determination by the Government not to compete this proposed requirement based upon responses to this notice is solely within the discretion of the Government. Information received will be considered solely for the purpose of determining whether to conduct a competitive procurement. In order to receive an award, Contractors must be registered and have valid certification through SAM.gov. Reference: 75N91023Q00042 on all correspondence.