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Purpose: Addressing lymphopenia in cancer patients has been suggested as a novel immunotherapeutic strategy. As interleukin-7 (IL-7) is necessary for proliferation of lymphocytes and to increase total lymphocyte count (TLC), IL-7 therapy has been attempted in various cancers. Here, we describe the clinical results of treatment of recurrent glioblastoma (GBM) with a long-acting engineered version of recombinant human IL-7 (rhIL-7-hyFc).
Methods: This prospective case series based on compassionate use was approved by the Ministry of Food and Drug Safety in South Korea. Primary outcomes were safety profile and TLC. Secondary outcomes were overall survival (OS) and progression-free survival (PFS).
Results: Among the 18 patients enrolled, 10 received rhIL-7-hyFc with temozolomide, 5 received rhIL-7-hyFc with bevacizumab, 1 received rhIL-7-hyFc with PCV chemotherapy, and 2 received rhIL-7-hyFc alone. Mean TLC of the enrolled patients after the first rhIL-7-hyFc treatment increased significantly from 1131 cells/mm (330-2989) at baseline to 4356 cells/mm (661-22,661). Higher TLCs were maintained while rhIL-7-hyFc was repeatedly administered. Median OS and PFS were 378 days (107-864 days) and 231 days (55-726 days), respectively.
Conclusion: Our study reports that IL-7 immunotherapy can restore and maintain TLC during treatment with various salvage chemotherapies in recurrent GBM patients without serious toxicity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067043 | PMC |
http://dx.doi.org/10.1002/cam4.5467 | DOI Listing |
Clin Transl Sci
May 2025
Department of Clinical Pharmacology and Therapeutics, Seoul National University Hospital, Seoul, Republic of Korea.
Recombinant human interleukin-7 hybrid Fc (rhIL-7-hyFc) is a homodimer of rhIL-7 fused to a hyFc. Exogenous IL-7 promotes T cell proliferation and increases lymphocyte count, making it a potential treatment option for lymphopenia and cancer. To improve therapeutic efficacy, rhIL-7-hyFc was developed as a long-acting IL-7.
View Article and Find Full Text PDFJ Immunother Cancer
February 2025
Division of Hematology and Medical Oncology, University of California San Francisco (UCSF) Helen Diller Comprehensive Cancer Center, San Francisco, California, USA.
Background: CD4 T-cell lymphocytopenia and immune dysfunction are factors that drive the onset and persistence of Kaposi sarcoma (KS) in people with (PWH) and without HIV. Standard chemotherapy agents for KS can contribute to increasing CD4 T cell lymphocytopenia. IL-7 is a cytokine that is essential in T-cell development, proliferation and homeostasis.
View Article and Find Full Text PDFJ Immunother Cancer
July 2024
National Cancer Institute, Bethesda, Maryland, USA
Background: Chimeric antigen receptor T-cell (CAR-T) therapy has achieved remarkable remission in patients with B-cell malignancies. However, its efficacy in treating solid tumors remains limited. Here, we investigated a combination therapy approach using an engineered long-acting interleukin (IL)-7 (rhIL-7-hyFc or NT-I7) and CAR-T cells targeting three antigens, glypican-2 (GPC2), glypican-3 (GPC3), and mesothelin (MSLN), against multiple solid tumor types including liver cancer, neuroblastoma, ovarian cancer, and pancreatic cancer in mice.
View Article and Find Full Text PDFLeukemia
December 2023
Division of Oncology, Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
T-cell malignancies are associated with frequent relapse and high morbidity, which is partly due to the lack of effective or targeted treatment options. To broaden the use of CAR-T cells in pan T-cell malignancies, we developed an allogeneic "universal" CD2-targeting CAR-T cell (UCART2), in which the CD2 antigen is deleted to prevent fratricide, and the T-cell receptor is removed to prevent GvHD. UCART2 demonstrated efficacy against T-ALL and CTCL and prolonged the survival of tumor-engrafted NSG mice in vivo.
View Article and Find Full Text PDFBlood Adv
October 2023
Division of Oncology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO.
Multiple myeloma (MM), a malignancy of mature plasma cells, remains incurable. B-cell maturation antigen (BCMA) is the lead protein target for chimeric antigen receptor (CAR) therapy because of its high expression in most MM, with limited expression in other cell types, resulting in favorable on-target, off tumor toxicity. The response rate to autologous BCMA CAR-T therapy is high; however, it is not curative and is associated with risks of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome.
View Article and Find Full Text PDF