Browsing by Subject "Adoptive cell therapy"

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    Go to the scene: TH9 cells superior migration ability to the lungs explains their exceptional anticancer efficacy
    (BMJ, 2025-04-28) Xu, Jiazhi; Apetoh, Lionel; Microbiology and Immunology, School of Medicine
    Antibodies against immune checkpoints are now routinely administered as a first line of treatment against metastatic lung cancer. Resistance to immune checkpoint inhibitors is, however, frequent, underscoring the need to find alternative treatments. Adoptive T-cell therapy has recently proven effective in treating patient's refractory to immune checkpoint inhibitors. This provides impetus to characterize the T-cell subsets best able to tackle tumors. The anticancer activities of IL-9-producing CD4 T helper cells (TH9 cells) were identified in melanoma in 2012. TH9 cells feature strong antimelanoma effects thanks to their production of interleukin (IL)-9 and the activation of innate and adaptive immune effectors. The ability of TH9 cells to prevent the growth of triple-negative breast cancer (TNBC) and osteosarcoma (OS), which commonly metastasize to the lungs, is elusive. In this commentary, we discuss the findings of Chen et al reported in the JITC demonstrating that TH9 cells are lung-tropic and eliminate TNBC and OS cells developing in the lungs. We also highlight how these investigations are in line with recent studies indicating that the adoptive transfer of IL-9-producing T cells eliminate aggressive cancers, including hematological tumors like leukemia and solid tumors such as glioblastoma. Altogether, these findings over the past 13 years support the clinical evaluation of TH9 cells in the adoptive therapy of cancer.
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    IND-Enabling Studies for a Clinical Trial to Genetically Program a Persistent Cancer-Targeted Immune System
    (American Association for Cancer Research, 2019-02-01) Puig-Saus, Cristina; Parisi, Giulia; Garcia-Diaz, Angel; Krystofinski, Paige E.; Sandoval, Salemiz; Zhang, Ruixue; Champhekar, Ameya S.; McCabe, James; Cheung-Lau, Gardenia C.; Truong, Nhat A.; Vega-Crespo, Agustin; Komenan, Marie Desiles S.; Pang, Jia; Macabali, Mignonette H.; Saco, Justin D.; Goodwin, Jeffrey L.; Bolon, Brad; Seet, Christopher S.; Montel-Hagen, Amelie; Crooks, Gay M.; Hollis, Roger P.; Campo-Fernandez, Beatriz; Bischof, Daniela; Cornetta, Kenneth; Gschweng, Eric H.; Adelson, Celia; Nguyen, Alexander; Yang, Lili; Witte, Owen N.; Baltimore, David; Comin-Anduix, Begonya; Kohn, Donald B.; Wang, Xiaoyan; Cabrera, Paula; Kaplan-Lefko, Paula J.; Berent-Maoz, Beata; Ribas, Antoni; Medical and Molecular Genetics, School of Medicine
    PURPOSE: To improve persistence of adoptively transferred T-cell receptor (TCR)-engineered T cells and durable clinical responses, we designed a clinical trial to transplant genetically-modified hematopoietic stem cells (HSCs) together with adoptive cell transfer of T cells both engineered to express an NY-ESO-1 TCR. Here, we report the preclinical studies performed to enable an investigational new drug (IND) application. EXPERIMENTAL DESIGN: HSCs transduced with a lentiviral vector expressing NY-ESO-1 TCR and the PET reporter/suicide gene HSV1-sr39TK and T cells transduced with a retroviral vector expressing NY-ESO-1 TCR were coadministered to myelodepleted HLA-A2/Kb mice within a formal Good Laboratory Practice (GLP)-compliant study to demonstrate safety, persistence, and HSC differentiation into all blood lineages. Non-GLP experiments included assessment of transgene immunogenicity and in vitro viral insertion safety studies. Furthermore, Good Manufacturing Practice (GMP)-compliant cell production qualification runs were performed to establish the manufacturing protocols for clinical use. RESULTS: TCR genetically modified and ex vivo-cultured HSCs differentiated into all blood subsets in vivo after HSC transplantation, and coadministration of TCR-transduced T cells did not result in increased toxicity. The expression of NY-ESO-1 TCR and sr39TK transgenes did not have a detrimental effect on gene-modified HSC's differentiation to all blood cell lineages. There was no evidence of genotoxicity induced by the lentiviral vector. GMP batches of clinical-grade transgenic cells produced during qualification runs had adequate stability and functionality. CONCLUSIONS: Coadministration of HSCs and T cells expressing an NY-ESO-1 TCR is safe in preclinical models. The results presented in this article led to the FDA approval of IND 17471.