Surgery Branch Cell Prep Core

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

The mission of this core laboratory is to provide support to the immunotherapy program established by the Surgery Branch of the National Cancer Institute. The laboratory has been managed by Dr. Hyunmi Halas. The main effort of the laboratory involves the production of large numbers of human anti-cancer T lymphocytes ex vivo, to treat patients with advanced metastatic cancer enrolled in Surgery Branch clinical trials. Cancer-targeting lymphocytes are either isolated directly from biopsied cancer metastases or are generated by genetically modifying T lymphocytes from a patient's blood. 26 patients each underwent a resection between 01-July-2021 and 01-Aug-2021, with 1 patient undergoing 3 independent resections. Of the 28 total resections processed by CPF, 15 resections provided potential source of tumor-infiltrating lymphocytes (TIL) and 13 were research resection from which initial fragments as potential source of tumor-infiltrating lymphocytes (TIL) were not performed. 70% of the 15 resections processed for fragments and subsequent TIL cells during this time provided sufficient tumor tissue to provide 11+ fragments, which were cryopreserved. 5 patient resections yielded reactive fragments with tumor specific reactivity to generate TIL cell which can be expanded in culture for potential treatments. 2 patient resections were identified reactive fragments as well as candidates for gene modified T lymphocyte therapies. 3 patients were found to not have reactive fragments but were found to have reactive neoantigens for gene modified T lymphocyte therapies identified from the tumor resection and gene modified to provide TCR known to recognize the cancer cells. Sixteen (16) cell products, delivered to patients enrolled on 5 clinical trials, were used to treat patients with autologous cell therapies generated by this core laboratory during FY20 through December 2020. A second critical function of this core lab is to distribute resected cancer tissue, leftover after the clinical treatment needs have been fulfilled. These samples are used by investigators in the Surgery Branch cell therapy program to evaluate the progress of each clinical trial, as well as to address research questions that identify changes that can be implemented to improve these trials. In addition, the samples from these trials facilitate research that generates new patient therapies. These research projects include 1) Transducing patients' T cells with genes whose products will better target tumors or enhance endogenous tumor activity, 2) Evaluating the ability of infused anticancer lymphocytes to function and survive in patients, 3) Identifying new cancer-associated antigens that can be targeted by anticancer cells, 4) Identifying novel patient specific antigens that are created by somatic mutations and selecting cultures that recognize these mutations for use in personalized T cell therapies 5) Identifying characteristics of infused anticancer cells that are associated with objective tumor regression, 6) Identifying characteristics of patients who are most likely to respond to anticancer T cell therapies, 7) Evaluating selected biological response modifiers tested in Surgery Branch clinical trials, 8) Evaluating new gene delivery systems such as the sleeping beauty transposon, 9) Producing dendritic cell vaccines that are pulsed with peptides representing a patient's own unique mutanome. Finally, the core laboratory maintains and curates all source documents, data, protocols, and expertise associated with cGMP manufacturing and the portion of the clinical translation of anticancer cell therapies carried out in the core lab. Due to the success of these therapies developed by the Surgery Branch, investigators within the Surgery Branch, intramural NCI laboratories, extramural regulatory agencies, industrial and academic partners, and other interested parties increasingly want access to these data, protocols, and advice. There is a need to develop new tools for curating data from older trials. There is a need to convert existing data into a format that can be read by newer software packages, it is essential that existing data generated in the core lab is not lost as older file types become obsolete. In response to two independent audits of the Surgery Branch cell production facility in early 2016, several programs and systems have been developed to comply with NIH, FDA and industry guidance/best practices. We have established an independent Quality Assurance (QA) program. This QA program functions independently of the cell processing facility and has the authority to stop production or prevent the release of cell-based therapies manufactured by the Surgery Branch cell processing facility when deemed necessary. Additionally, the QA program performs internal audits to ensure compliance with SOPs and procedures and approves the new employee and annual training of the facility staff. These programs ensure that patient safety, along with generating clinically effective anti-cancer cells, is a primary concern of all employees involved in the manufacture of cell-based therapies. A crucial component of the QA program is document control. The document management system used by NCI SB Operations and Quality Assurance group, MediaLab, is employed to ensure that all staff has access to the most update version of SOPs, forms, and regulations used by the cell processing facility. MediaLab allows full tracking of all document versions and changes to ensure better compliance and training for all cell processing facility SOPs and regulations. A cleaning service that specializes in cleanroom sanitation has been contracted by the Office of Research Support and Compliance (ORSC) to clean all NIH aseptic facilities, including NCI SB manufacturing and support facilities, Trailer 10B and T30. The effectiveness of this program is tracked with a newly implemented environmental monitoring program that tracks and trends air and surface quality/cleanliness within the manufacturing areas of the facility. This program identifies potential sources of microbial contamination before they can impact the overall manufacturing operation. The final component of efforts to develop a robust QA system is the development of a materials management program. Materials management controls the acquisition, quarantine, acceptance, and release of all manufacturing materials. The goal of this program is to increase patient safety by improving documentation of source, lot number and expiration date and quality control of all materials used to manufacture cell products within the Surgery Branch cell processing facility. This program is crucial in identifying patient's whose past or pending treatments are associated with a manufacturer recall. The materials management program allows all patients impacted by a recall to be identified and monitored for adverse events. Dr. Xu Zhao is currently the facility manager of the Cell Production Facility at the Surgery Branch of the National Cancer Institute in Bethesda, USA, where the main interest is to establish successful gene therapies and cell-based treatments for patients with advanced metastatic cancer.