Surgery Branch Cell Prep Core

Division Of Basic Sciences - Nci

Investigators

Linked publications & trials

Abstract

The mission of the TIL lab/Cell Production Facility (CPF) core services 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. 59 patients underwent a resection between 01-July-2022 and 01-Aug-2023 with the purpose of generating clinical tumor-infiltrating lymphocyte (TIL) cultures for screening and potential patient treatment. Of the 59 total resections processed under cGMP conditions by CPF to generate tumor-infiltrating lymphocytes (TIL) culture for potential treatments. 17 of the 59 tumors processed yielded positive screens for reactive TIL to be used as potential therapy and 11 are pending screening. In addition to the clinical resections, 25 tumors were handled by the TIL lab for research purposes. These samples were documented and transitioned to the SB research team for tumor neoantigen identification. 24 of the 55 patients did not receive TIL treatments due to several reasons including patient ineligibility, insufficient reactivity in the patient's TIL fragments, or the patient was deceased. During the reporting period, 13 patients were treated with final TIL therapies initially grown by the TIL lab/Cell Processing Facility, screened by SB researchers for reactivity, and manufactured as a final cell product under strict regulation by the TIL lab in the GMP T30 facility. A second critical core function of CPR is to distribute resected tumor 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 or improvements to the current systems. A third critical function CPF is responsible for is the processing of all starting materials for patient treatments. In addition to the tumor resections for clinical TIL cultures, all patient and healthy donor phereses for peripheral blood mononuclear cells are processed under cGMP condition by CPF. During the reporting period, 140 pheresis collections and 6 healthy volunteer serum collections (of no fewer than 4 donors) were processed. The processed PBMCs are used for neoantigen screening, as starting materials for autologous gene therapy cellular treatments, and for research purposes throughout the branch. 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 NCI SB 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. The TIL Lab has been working to assist in the transition to a new electronic management system, MasterControl, to tie into the system used by the greater NIH cGMP groups including ORSC, the NIH GMP oversight office. 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 facility, T30. The final component of efforts to develop a robust GMP environment is the development of a materials management and facility oversight program. Materials management controls the acquisition, quarantine, acceptance, and release of all manufacturing materials while the facility oversight ensure the manufacturing facility operate to the design cleanroom specifications required by the FDA and meet the compliance requirements for cGMP manufacturing of phase 1 and 2 cellular products. 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 or in the event of a facility issue. The materials management and facility oversight 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.