Engagement of the OX-40 receptor in vivo enhances antitumor immunity.

نویسندگان

  • A D Weinberg
  • M M Rivera
  • R Prell
  • A Morris
  • T Ramstad
  • J T Vetto
  • W J Urba
  • G Alvord
  • C Bunce
  • J Shields
چکیده

The OX-40 receptor (OX-40R), a member of the TNFR family, is primarily expressed on activated CD4+ T lymphocytes. Engagement of the OX-40R, with either OX-40 ligand (OX-40L) or an Ab agonist, delivers a strong costimulatory signal to effector T cells. OX-40R+ T cells isolated from inflammatory lesions in the CNS of animals with experimental autoimmune encephalomyelitis are the cells that respond to autoantigen (myelin basic protein) in vivo. We identified OX-40R+ T cells within primary tumors and tumor-invaded lymph nodes of patients with cancer and hypothesized that they are the tumor-Ag-specific T cells. Therefore, we investigated whether engagement of the OX-40R in vivo during tumor priming would enhance a tumor-specific T cell response. Injection of OX-40L:Ig or anti-OX-40R in vivo during tumor priming resulted in a significant improvement in the percentage of tumor-free survivors (20-55%) in four different murine tumors derived from four separate tissues. This anti-OX-40R effect was dose dependent and accentuated tumor-specific T cell memory. The data suggest that engagement of the OX-40R in vivo augments tumor-specific priming by stimulating/expanding the natural repertoire of the host's tumor-specific CD4+ T cells. The identification of OX-40R+ T cells clustered around human tumor cells in vivo suggests that engagement of the OX-40R may be a practical approach for expanding tumor-reactive T cells and thereby a method to improve tumor immunotherapy in patients with cancer.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Therapeutic efficacy of OX-40 receptor antibody depends on tumor immunogenicity and anatomic site of tumor growth.

The OX-40 receptor (OX-40R) is a cell surface glycoprotein of the tumor necrosis factor receptor family that is expressed primarily on activated CD4 T cells. Engagement of OX-40R by the OX-40 ligand (OX-40L) is known to costimulate the production of cytokines by activated T lymphocytes and to rescue effector T cells from activation-induced cell death. It was previously reported that in vivo lig...

متن کامل

Gold nanoparticle-induced sonosensitization enhances the antitumor activity of ultrasound in colon tumor-bearing mice

Introduction: Light-driven cancer therapy strategies (e.g. photodynamic therapy and photothermal therapy) have undergone remarkable progress in recent years, but they still suffer from a serious drawback of limited penetration depth of light in tissue. As a non-invasive and non- ionizing radiation, ultrasound can be focused remotely, transferring acoustic energy deep in the bo...

متن کامل

Scavenger receptor-A negatively regulates antitumor immunity.

The scavenger receptor-A (SR-A), originally recognized by its ability to internalize modified lipoproteins, has largely been studied in relation to atherosclerosis as well as innate immunity against pathogen infection. SR-A was recently shown to be a receptor on antigen-presenting cell for heat shock protein (HSP) and was implicated in the cross-presentation of HSP-chaperoned antigens. Here, we...

متن کامل

Anti-human CD40 monoclonal antibody therapy is potent without FcR crosslinking

Antibody agonists targeting tumor necrosis factor (TNF) superfamily receptors, including CD40, are being tested therapeutically as anticancer agents. Studies in mice have shown that anti-CD40 monoclonal antibody (mAb) requires Fc-receptor (FcR) engagement to activate antitumor immunity. In contrast, we have reported that clinically active anti-human CD40 mAb CP-870,893 does not require FcR cros...

متن کامل

ذخیره 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 نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Journal of immunology

دوره 164 4  شماره 

صفحات  -

تاریخ انتشار 2000