Tumor ablation by gene-modified T cells in the absence of autoimmunity.
نویسندگان
چکیده
Adoptive immunotherapy involving genetic modification of T cells with antigen-specific, chimeric, single-chain receptors is a promising approach for the treatment of cancer. To determine whether gene-modified T cells could induce antitumor effects without associated autoimmune pathology, we assessed the ability of T cells expressing an anti-Her-2 chimeric receptor to eradicate tumor in Her-2 transgenic mice that express human Her-2 as a self-antigen in brain and mammary tissues. In adoptive transfer studies, we demonstrated significant improvement in the survival of mice bearing Her-2(+) 24JK tumor following administration of anti-Her-2 T cells compared with control T cells. The incorporation of a lymphoablative step prior to adoptive transfer of anti-Her-2 T cells and administration of IL-2 were both found to further enhance survival. The reduction in tumor growth was also correlated with localization of transferred T cells at the tumor site. Furthermore, an antigen-specific recall response could be induced in long-term surviving mice following rechallenge with Her-2(+) tumor. Importantly, antitumor effects were not associated with any autoimmune pathology in normal tissue expressing Her-2 antigen. This study highlights the therapeutic potential of using gene-engineered T cells as a safe and effective treatment of cancer.
منابع مشابه
CTLA4 Gene Variants in Autoimmunity and Cancer: a Comparative Review
Gene association studies are less appealing in cancer compared to autoimmune diseases. Complexity, heterogeneity, variation in histological types, age at onset, short survival, and acute versus chronic conditions are cancer related factors which are different from an organ specific autoimmune disease, such as Grave’s disease, on which a large body of multicentre data is accumulated. For years t...
متن کاملMicroenvironment and Immunology Tumor Ablation by Gene-Modified T Cells in the Absence of Autoimmunity
Adoptive immunotherapy involving genetic modification of T cells with antigen-specific, chimeric, singlechain receptors is a promising approach for the treatment of cancer. To determine whether gene-modified T cells could induce antitumor effects without associated autoimmune pathology, we assessed the ability of T cells expressing an anti-Her-2 chimeric receptor to eradicate tumor in Her-2 tra...
متن کاملSTAT3 as a Key Factor in Tumor Microenvironment and Cancer Stem Cell
Background Recent studies revealed that tumor-associated macrophages (TAMs) play a decisive role in the regulation of tumor progression by manipulating tumor oncogenesis, angiogenesis and immune functions within tumor microenvironments. Signal transducer and activator of transcription 3 (STAT3), which is a point of convergence for numerous oncogenic signalling pathways, is constitutively activ...
متن کاملPET and MRI-guided focused ultrasound surgery for hypoxic-tissue ablation combined with radiotherapy in solid tumors
Background: The rationale was to develop an ablation approach to destroy regions of tumor resistant to radiation and thus reduce the time required for whole tumor ablation, while improving overall tumor control after radiotherapy. Materials and Methods: The system is composed of a micro positron emission tomography (mPET), 7T magnetic resonance imaging (MRI), and a customized MRI-compatible foc...
متن کاملPITUITARY DEPENDENT CUSHING\'S SYNDROME IN IRAN
During a 5-year experience with 32 adrenal tumors with different basic problems in the Department of Endocrinology , Taleghani Hospital, 25 were found pituitary dependent Cushing's syndrome, "Cushing's disease." The treatment of patients with Cushing's disease depends on the presence or absence of pituitary tumor. Ifno pituitary tumor is demonstrated, irradiation can be given to the pituit...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Cancer research
دوره 70 23 شماره
صفحات -
تاریخ انتشار 2010