NDLI: Synergistic Chemoimmunotherapy of Epithelial Ovarian Cancer Using ErbB-Retargeted T Cells Combined with Carboplatin.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Van Der Stegen, Sjoukje J. C. Maher, John Parente-Pereira, Ana C. Whilding, Lynsey M. Davies, David M. Van Schalkwyk, May C. I. Wilkie, Scott Ghaem-Maghami, Sadaf Brewig, Nancy
Description	Country affiliation: United kingdom Author Affiliation: Parente-Pereira AC ( Department of Research Oncology, King's College London, King's Health Partners Integrated Cancer Centre, Guy's Hospital Campus, London SE1 9RT, United Kingdom.)
Abstract	Epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy, underscoring the need for better therapies. Adoptive immunotherapy using genetically targeted T cells represents a promising new treatment for hematologic malignancies. However, solid tumors impose additional obstacles, including the lack of suitable targets for safe systemic therapy and the need to achieve effective T cell homing to sites of disease. Because EOC undergoes transcÅ lomic metastasis, both of these challenges may be circumvented by T cell administration to the peritoneal cavity. In this study, we describe such an immunotherapeutic approach for EOC, in which human T cells were targeted against the extended ErbB family, using a chimeric Ag receptor named T1E28z. T1E28z was coexpressed with a chimeric cytokine receptor named 4 ß (combination termed T4), enabling the selective ex vivo expansion of engineered T cells using IL-4. Unlike control T cells, T4(+) T cells from healthy donors and patients with EOC were activated by and destroyed ErbB(+) EOC tumor cell lines and autologous tumor cultures. In vivo antitumor activity was demonstrated in mice bearing established luciferase-expressing SKOV-3 EOC xenografts. Tumor regression was accompanied by mild toxicity, manifested by weight loss. Although efficacy was transient, therapeutic response could be prolonged by repeated T cell administration. Furthermore, prior treatment with noncytotoxic doses of carboplatin sensitized SKOV-3 tumors to T4 immunotherapy, promoting enhanced disease regression using lower doses of T4(+) T cells. By combining these approaches, we demonstrate that repeated administration of carboplatin followed by T4(+) T cells achieved optimum therapeutic benefit in the absence of significant toxicity, even in mice with advanced tumor burdens.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	5
Volume Number	191
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2013-09-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antineoplastic Agents Administration & Dosage Carboplatin Immunotherapy, Adoptive Neoplasms, Glandular And Epithelial Therapy Ovarian Neoplasms Receptor, Epidermal Growth Factor Immunology T-lymphocytes Animals Combined Modality Therapy Drug Therapy Flow Cytometry Mice Recombinant Fusion Proteins Transduction, Genetic Xenograft Model Antitumor Assays Research Support, Non-u.s. Gov't Research Support, U.s. Gov't, Non-p.h.s. Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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