Immunotherapy with chimeric NKG2D receptors leads to long-term tumor-free survival and development of host antitumor immunity in murine ovarian cancer.

Abstract	Ovarian cancer is one of the leading causes of cancer death in women and the development of novel therapies is needed to complement the standard treatment options such as chemotherapy and radiation. In this study, we show that treatment with T cells expressing a chimeric NKG2D receptor (chNKG2D) was able to lead to long-term, tumor-free survival in mice bearing established ovarian tumors. Tumor-free mice were able to reject a rechallenge with ovarian tumor cells 225 days after original tumor injection. In addition, chNKG2D T cell treatment induced specific host immune responses to ovarian tumor cells, including the development of both CD8+ and CD4+ T cell tumor-specific memory responses. The chNKG2D T cells reduced the ovarian tumor burden using both cytotoxic and cytokine-dependent pathways. Specifically, chNKG2D T cell expression of perforin, GM-CSF, and IFN-gamma were essential for complete antitumor efficacy.
Authors	Amorette Barber, Tong Zhang, Charles L Sentman
Journal	Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 180 Issue 1 Pg. 72-8 (Jan 01 2008) ISSN: 0022-1767 [Print] United States
PMID	18097006 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Klrk1 protein, mouse NK Cell Lectin-Like Receptor Subfamily K Receptors, Immunologic Receptors, Natural Killer Cell Recombinant Fusion Proteins Perforin Interferon-gamma Granulocyte-Macrophage Colony-Stimulating Factor
Topics	Animals Disease-Free Survival Female Granulocyte-Macrophage Colony-Stimulating Factor (metabolism) Immunotherapy, Adoptive (methods) Interferon-gamma (metabolism) Mice NK Cell Lectin-Like Receptor Subfamily K Ovarian Neoplasms (therapy) Perforin (metabolism) Receptors, Immunologic (genetics, metabolism) Receptors, Natural Killer Cell Recombinant Fusion Proteins (genetics, metabolism) T-Lymphocytes (immunology, transplantation) Tumor Burden

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