Surgery Branch Cell Prep Core

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

The mission and services of the SB Cell Prep Core portion of the TIL lab/CPF is to provide support to the immunotherapy clinical and research program established by NCI SB under cGMP compliance and NIH requirements for aseptic processing facilities. All materials are handled, processed and stored under cGMP conditions with oversight from the SB QA group and the CC Office of Research Support and Compliance. The main effort involves processing and generating materials to support the production of large numbers of patient specific anti-cancer T lymphocytes ex vivo for potential individualized treatment to patients with advanced metastatic cancer enrolled in SB clinical trials. These are either isolated directly from biopsied cancer metastases to allow for the expansion of tumor infiltrating lymphocytes (TIL) when a patient's resected tumor tissue is properly processed and cultured or by genetically modifying T lymphocytes isolated from a patient's blood. Processing and expansion of primary TIL cultures was established from 41 tumor resections from 03 Jul 2024 and 15 Jul 2025. The TIL established from this process is referred to as "initial" TIL cultures and serves two primary purposes: tumor reactivity/ neoantigen identification by the SB research program and potential patient adoptive cell transfer (ACT) treatment. Of the 42 total resections processed under cGMP conditions, 26 tumors processed yielded positive screens for reactive TIL for potential ACTs, 1 did not expand due to insufficient tumor tissue, and 4 resections are currently pending screening. As of July 2025, 12 of the 25 patients with positive screens were treated with final TIL therapies (ZIC BC 011569) and 16, including some with positive screens, were not treated with TIL due to several reasons including patient ineligibility, insufficient reactivity in the patient's TIL fragments, or the patient was deceased. TILs are also screened for neoantigens for potential genetically modified ACT therapies. After sequencing the identified receptors, retroviral vectors are used to genetically modify patient autologous peripheral blood lymphocytes to express the tumor neoantigen reactive receptor under the genetically modified adoptive cell therapy protocols within the SB. The PBL required for neoantigen screening and as starting material to produce patient specific genetically modified ACT therapies under ZIC BC 011569 is acquired from an apheresis collection. The apheresis is processed under GMP in the cleanroom facility and cryopreserved in the SB biorepository managed by CPF under ZIC BC 010905 and ZIC BC 011569. During the reporting period, 111 apheresis collections were processed. All post treatment follow-up samples collected from treated patients are inventoried by and largely processed by the CPF core (ZIC BC 010905) and are managed by CPF team. These samples, in addition to final product samples generated and cryopreserved under ZIC BC 011569, are used by the SB research program to evaluate the clinical trials and address research questions. 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 anti-tumor activity, 2) Evaluating the persistence of infused cells to function and survive in patients, 3) Identifying new cancer-associated antigens , 4) Identify characteristics of infused cells that are associated with objective tumor regression, 5) Identifying characteristics of patients who are most likely to respond to targeted T cell therapies, 6) Evaluating selected biological response modifiers tested in SB clinical trials, 7) Working across groups for new gene delivery systems or improvements to the current systems. The success and achievements of CPF for ZIC BC 010905 is connected to the work performed under ZIC BC 011569. The merits and advancements for both projects are achieved with the infrastructure necessary to support operations under the required regulations necessary for patient safety and GMP regulations. The infrastructure required to ensure efficiency and success includes adequate levels of qualified staff, access to reagents and consumables for manufacturing and testing, regulatory and product oversight (via QA and quality control testing), and multiple internal and external services to ensure the facility, staff and patients are properly protected. These and other resources are needed to efficiently serve the patients eligible for SB clinical trials in a timely manner with the ability to pivot and respond to changes to the clinical schedule and onboard new treatment protocols while remaining in compliance. The key results/achievements related to clinical impact are reported and tracked by the clinical team. The scientific research findings and the outcomes to treatment protocols result in high impact publications (see H. Halas publication lists) which include several members of CPF as authors and acknowledgement of CPF/TIL lab as a critical resources and service. CPF's work and collaboration with the Clinical Center Department of Laboratory Medicine to improve and onboard an NIH wide testing systems was recognized with the NIH Clinical 2024 CEO Awards. This was presented to several members of CPF for a collaboration that spanned ZIC BC 010905 and ZIC BC 011569.