Intraperitoneal Monocytes plus IFNs as a Novel Cellular Immunotherapy for Ovarian Cancer: Mechanistic Characterization and Results from a Phase I Clinical Trial.

Autor:	Green DS; Women's Malignancies Branch, Center for Cancer Research (CCR), NCI, Bethesda, Maryland.; Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, NIH, Bethesda, Maryland., Ning F; Women's Malignancies Branch, Center for Cancer Research (CCR), NCI, Bethesda, Maryland., Duemler A; Women's Malignancies Branch, Center for Cancer Research (CCR), NCI, Bethesda, Maryland., Myers TG; Genomic Technologies Section, National Institutes of Allergy and Infectious Diseases, NIH, Bethesda, Maryland., Trewhitt K; Women's Malignancies Branch, Center for Cancer Research (CCR), NCI, Bethesda, Maryland., Ekwede I; Women's Malignancies Branch, Center for Cancer Research (CCR), NCI, Bethesda, Maryland., McCoy A; Women's Malignancies Branch, Center for Cancer Research (CCR), NCI, Bethesda, Maryland., Houston N; Women's Malignancies Branch, Center for Cancer Research (CCR), NCI, Bethesda, Maryland., Lee JM; Women's Malignancies Branch, Center for Cancer Research (CCR), NCI, Bethesda, Maryland., Lipkowitz S; Women's Malignancies Branch, Center for Cancer Research (CCR), NCI, Bethesda, Maryland., Zimmer A; Women's Malignancies Branch, Center for Cancer Research (CCR), NCI, Bethesda, Maryland., Pavelova M; Women's Malignancies Branch, Center for Cancer Research (CCR), NCI, Bethesda, Maryland., Villanueva EN; Women's Malignancies Branch, Center for Cancer Research (CCR), NCI, Bethesda, Maryland., Smith L; Women's Malignancies Branch, Center for Cancer Research (CCR), NCI, Bethesda, Maryland., Blakely A; Surgical Oncology Program, Center for Cancer Research (CCR), NCI, Bethesda, Maryland., Casablanca Y; Gynecologic Oncology, Walter Reed National Military Medical Center, Bethesda, Maryland., Highfill SL; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, NIH, Bethesda, Maryland., Stroncek DF; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, NIH, Bethesda, Maryland., Collins-Johnson N; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, NIH, Bethesda, Maryland., Panch S; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, NIH, Bethesda, Maryland., Procter J; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, NIH, Bethesda, Maryland., Pham C; Center for Cellular Engineering, Department of Transfusion Medicine, Clinical Center, NIH, Bethesda, Maryland., Korrapati S; Women's Malignancies Branch, Center for Cancer Research (CCR), NCI, Bethesda, Maryland., Holland SM; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland., Rosen LB; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland., Nunes AT; Women's Malignancies Branch, Center for Cancer Research (CCR), NCI, Bethesda, Maryland., Zoon KC; Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, NIH, Bethesda, Maryland., Cole CB; Women's Malignancies Branch, Center for Cancer Research (CCR), NCI, Bethesda, Maryland., Annunziata CM; Women's Malignancies Branch, Center for Cancer Research (CCR), NCI, Bethesda, Maryland.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2023 Jan 17; Vol. 29 (2), pp. 349-363.
DOI:	10.1158/1078-0432.CCR-22-1893
Abstrakt:	Purpose: Ovarian cancer is the most lethal gynecologic cancer and intrinsically resistant to checkpoint immunotherapies. We sought to augment innate immunity, building on previous work with IFNs and monocytes. Patients and Methods: Preclinical experiments were designed to define the mechanisms of cancer cell death mediated by the combination of IFNs α and γ with monocytes. We translated these preclinical findings into a phase I trial of autologous IFN-activated monocytes administered intraperitoneally to platinum-resistant or -refractory ovarian cancer patients. Results: IFN-treated monocytes induced caspase 8-dependent apoptosis by the proapoptotic TRAIL and mediated by the death receptors 4 and 5 (DR4 and DR5, respectively) on cancer cells. Therapy was well tolerated with evidence of clinical activity, as 2 of 9 evaluable patients had a partial response by RECIST criteria, and 1 additional patient had a CA-125 response. Upregulation of monocyte-produced TRAIL and cytokines was confirmed in peripheral blood. Long-term responders had alterations in innate and adaptive immune compartments. Conclusions: Given the mechanism of cancer cell death, and the acceptable tolerability of the clinical regimen, this platform presents a possibility for future combination therapies to augment anticancer immunity. See related commentary by Chow and Dorigo, p. 299. (©2022 American Association for Cancer Research.)
Databáze:	MEDLINE
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