Clinical-Grade Gamma-Retrovirus Vector Encoding an Anti-CD319 Chimeric Antigen Receptor
Contracting Office Address
Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Office of Acquisitions, 9609 Medical Center Drive, Room 1E134, Bethesda, MD 20892, UNITED STATES
Description
The National Cancer Institute (NCI), Center for Cancer Research (CCR), Experimental Transplantation and Immunology Branch (ETIB) plans to procure on a sole source basis a Clinical-Grade Gamma-Retrovirus Vector Encoding an Anti-CD319 Chimeric Antigen Receptor with Cincinnati Children's Hospital, 3333 Burnet Av. S11.400, Cincinnati, OH 45229.
This acquisition will be processed in accordance with the simplified acquisition procedures as authorized by FAR Part 13.106-1 (b) (1) and is exempt from the requirements of FAR part 6. The North American Industry Classification System Code is 622110 and the business size standard is $38.5 million.
Only one award will be made as a result of this solicitation. This will be awarded as a firm fixed price type contract.
It has been determined there are no opportunities to acquire green products or services for this procurement.
The Experimental Transplantation and Immunology Branch is dedicated to coordinated efforts in basic, preclinical and clinical investigations in the areas of immunotherapy, immune reconstitution, T cell biology, hematopoiesis, and hematopoietic stem cell transplantation. The goal is to generate information from basic and preclinical investigations to develop new, curative hematopoietic stem cell transplant-based therapies for cancer. Information from new treatment protocols (including novel endpoints generated in the course of basic/preclinical research) is used to generate new questions and studies in the basic and preclinical research efforts. The branch emphasizes excellence in these endeavors and acts to maximize strengths present in the community at large by vigorous intramural and extramural interactions and collaborations.
Chimeric antigen receptors (CARs) are fusion proteins containing antigen-recognition domains and T-cell activation domains. When T cells are genetically modified to express CARs, they gain the ability to specifically recognize an antigen and to kill cells expressing the antigen. In previous clinical trials, CAR-expressing T cells have been shown to have potent anti-malignancy activity against leukemia and lymphoma. In particular, CARs targeting CD19 have been shown to be effective in multiple clinical trials, but extension of CAR T-cell therapies to other malignancies has not yet been widespread. The NCI has constructed a CAR targeting CD319. This CAR is encoded by a gamma-retroviral vector. The NCI plans to use this transiently-produced gamma-retroviral gene-therapy vector to genetically modify T cells from patients with multiple myeloma. Multiple myeloma cells express CD319. The NCI will use the T cells genetically modified to express the anti-CD319 CAR to treat patients with multiple myeloma.
The vector will encode a chimeric antigen receptor (CAR) recognizing a multiple myeloma antigen. The intended use of this vector is to transduce patient T cells. These T cells will be administered as a treatment for multiple myeloma in a clinical trial. The vector will be gibbon ape leukemia virus (GALV) pseudotyped. The vector will be generated in 293T cells. The NCI will provide a plasmid encoding the CAR also known as the expression construct. This requirement includes full testing of the vector to satisfy requirements for clinical use including testing for replication-competent retroviruses (RCR), testing for mycoplasma, syroplasma, endotoxin, adventitious virus, residual plasmid DNA, residual cellular DNA, transfer of E1A sequences, transfer of SV40 sequences, and testing for bacterial sterility.
The produced vector must be able to transduce primary human T cells to a degree that at least 20% of primary human T cells will express the chimeric antigen receptor gene on the T-cell surface as measured by flow cytometry. Shipment of the gamma-retroviral vector from the site of production to a storage site is not included in this contract, but temporary storage of the vector for up to 6 months shall be included.
SCOPE
The NCI plans to conduct clinical trials of a novel anti-CD319 CAR encoded by the gamma-retroviral vector. This will require production of a clinical-grade gamma-retroviral vector. This work has potential to be an important advance in the treatment of multiple myeloma. New treatments are urgently needed by patients with multiple myeloma.
Production of 20 liters of clinical-grade gamma-retroviral gene-therapy vector for use in a clinical trial. This gene therapy vector will encode and anti-CD319 chimeric antigen receptor and be used to treat multiple myeloma. The Contractor will provide packaging plasmids. The Contractor shall provide documentation of vector test results for inclusion in applications to the Food and Drug Administration.
CONTRACT REQUIREMENTS/ AND PERSONNEL QUALIFICATIONS
Personnel shall have training and experience in production of clinical-grade, transiently-produced gamma-retroviral gene-therapy vectors.
Vector Production facility additional personnel include eight additional employees dedicated to vector manufacturing, three employees dedicated to cleanroom operations and quality control and three Quality Assurance personnel supporting the Translational Core Labs including the Vector Production Facility. The Quality Assurance personnel report through the Office of Research Compliance and Regulatory Affairs within the Cincinnati Children's Research Foundation.
The VPF is a Manufacturing Facility for the production of viral vectors in support of Clinical Trials in compliance with current Good Manufacturing Practices (cGMP).
The Contractor shall:
• Contractor shall produce 20 liters of clinical-grade gamma-retroviral gene-therapy vector for use in a clinical trial
• Contractor personnel shall have training and experience in production of clinical-grade, transiently-produced gamma-retroviral gene-therapy vectors
• Contractor personnel shall be trained in cleanroom behavior and are required to participate in the gowning qualification program and are qualified by media fill prior to preparing any production
• All raw materials used in manufacturing must be approved by the FDA for human use, or are used as part of an Investigational New Drug (IND) FDA approved protocol
• Perform all aseptic manipulations inside ISO Class 5 Biological Safety Cabinets (BSCs) in the labs. All BSCs shall be equipped with a continuous particle monitoring system that is tied into the central alarm system.
This requirement is for a specific type of gene-therapy vector that is not available from any other known source than the Vector Production Facility of the Cincinnati Children's Hospital (CCH). The requirements are for a clinical-grade, transiently-produced gamma-retroviral gene-therapy vector. It must be emphasized that the vector for this project must be clinical-grade for use in a human clinical trial. It must be suitable for research conducted under an Investigational New Drug Application approved by the FDA.
This notice is not a request for competitive quotation. However, if any interested party, especially small businesses, believes it can meet the above requirement, it may submit a capability statement, proposal, or quotation, which shall be considered by the agency. The statement of capabilities 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. Responses must be received in the contracting office by 5:00 PM EST, on April 27, 2018. All responses and questions can be emailed to Kimesha Leake, Contracting Officer via electronic mail at kimesha.leake@nih.gov. 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 in the System for Award Management (SAM) through sam.gov. Reference: N02RC82554-24 on all correspondence.
Kimesha Leake, Contracting Officer, Phone 2402765669, Email kimesha.leake@nih.gov - Reyes Rodriguez, Contracting Officer, Phone 240-276-5442, Email reyes.rodriguez@nih.gov
