Photothermal Prussian blue nanoparticles generate potent multi-targeted tumor-specific T cells as an adoptive cell therapy.

Autor: Sweeney EE; Department of Biochemistry & Molecular Medicine, School of Medicine and Health Sciences George Washington University Washington District of Columbia USA.; Center for Cancer and Immunology Research Children's National Hospital Washington District of Columbia USA., Sekhri P; Center for Cancer and Immunology Research Children's National Hospital Washington District of Columbia USA.; The Integrated Biomedical Sciences Program, School of Medicine and Health Sciences George Washington University Washington District of Columbia USA., Muniraj N; The Integrated Biomedical Sciences Program, School of Medicine and Health Sciences George Washington University Washington District of Columbia USA., Chen J; Center for Cancer and Immunology Research Children's National Hospital Washington District of Columbia USA., Feng S; Center for Cancer and Immunology Research Children's National Hospital Washington District of Columbia USA.; George Washington Cancer Center, School of Medicine and Health Sciences George Washington University Washington District of Columbia USA., Terao J; The Integrated Biomedical Sciences Program, School of Medicine and Health Sciences George Washington University Washington District of Columbia USA., Chin SJ; Center for Cancer and Immunology Research Children's National Hospital Washington District of Columbia USA.; George Washington Cancer Center, School of Medicine and Health Sciences George Washington University Washington District of Columbia USA., Schmidt DE; Center for Cancer and Immunology Research Children's National Hospital Washington District of Columbia USA., Bollard CM; Center for Cancer and Immunology Research Children's National Hospital Washington District of Columbia USA.; The Integrated Biomedical Sciences Program, School of Medicine and Health Sciences George Washington University Washington District of Columbia USA., Cruz CRY; Center for Cancer and Immunology Research Children's National Hospital Washington District of Columbia USA.; The Integrated Biomedical Sciences Program, School of Medicine and Health Sciences George Washington University Washington District of Columbia USA., Fernandes R; Center for Cancer and Immunology Research Children's National Hospital Washington District of Columbia USA.; George Washington Cancer Center, School of Medicine and Health Sciences George Washington University Washington District of Columbia USA.; Department of Medicine, School of Medicine and Health Sciences George Washington University Washington District of Columbia USA.
Jazyk: angličtina
Zdroj: Bioengineering & translational medicine [Bioeng Transl Med] 2023 Dec 22; Vol. 9 (3), pp. e10639. Date of Electronic Publication: 2023 Dec 22 (Print Publication: 2024).
DOI: 10.1002/btm2.10639
Abstrakt: Prussian blue nanoparticle-based photothermal therapy (PBNP-PTT) is an effective tumor treatment capable of eliciting an antitumor immune response. Motivated by the ability of PBNP-PTT to potentiate endogenous immune responses, we recently demonstrated that PBNP-PTT could be used ex vivo to generate tumor-specific T cells against glioblastoma (GBM) cell lines as an adoptive T cell therapy (ATCT). In this study, we further developed this promising T cell development platform. First, we assessed the phenotype and function of T cells generated using PBNP-PTT. We observed that PBNP-PTT facilitated CD8+ T cell expansion from healthy donor PBMCs that secreted IFNγ and TNFα and upregulated CD107a in response to engagement with target U87 cells, suggesting specific antitumor T cell activation and degranulation. Further, CD8+ effector and effector memory T cell populations significantly expanded after co-culture with U87 cells, consistent with tumor-specific effector responses. In orthotopically implanted U87 GBM tumors in vivo, PBNP-PTT-derived T cells effectively reduced U87 tumor growth and generated long-term survival in >80% of tumor-bearing mice by Day 100, compared to 0% of mice treated with PBS, non-specific T cells, or T cells expanded from lysed U87 cells, demonstrating an enhanced antitumor efficacy of this ATCT platform. Finally, we tested the generalizability of our approach by generating T cells targeting medulloblastoma (D556), breast cancer (MDA-MB-231), neuroblastoma (SH-SY5Y), and acute monocytic leukemia (THP-1) cell lines. The resulting T cells secreted IFNγ and exerted increased tumor-specific cytolytic function relative to controls, demonstrating the versatility of PBNP-PTT in generating tumor-specific T cells for ATCT.
Competing Interests: Catherine M. Bollard (CMB) is a past scientific advisory board member for NexImmune and Repertoire Immune Medicines, both antigen‐specific T cell companies. CMB has stock or ownership in Cabaletta Bio, Catamaran Bio, and NexImmune. Elizabeth E. Sweeney (EES) and Rohan Fernandes (RF) are co‐founders of ImmunoBlue, a biotechnology company focused on developing PBNP‐based nanoimmunotherapies. EES, Palak Sekhri, C. Russell Y. Cruz, and RF have jointly filed a patent application protecting the work described in this manuscript.
(© 2023 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)
Databáze: MEDLINE
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