CTLA-4 blockade during dendritic cell based booster vaccination influences dendritic cell survival and CTL expansion

نویسندگان

  • Anders E Pedersen
  • Franca Ronchese
چکیده

Dendritic cells (DCs) are potent antigen-presenting cells and critical for the priming of CD8+ T cells. Therefore the use of these cells as adjuvant cells has been tested in a large number of experimental and clinical vaccination studies, in particular cancer vaccine studies. A number of protocols are emerging that combine vaccination with CTL expanding strategies, such as e.g. blockade of CTLA-4 signalling. On the other hand, the lifespan and in vivo survival of therapeutic DCs have only been addressed in a few studies, although this is of importance for the kinetics of CTL induction during vaccination. We have previously reported that DCs loaded with specific antigens are eliminated by antigen specific CTLs in vivo and that this elimination affects the potential for in vivo CTL generation. We now show that CTLA-4 blockade increases the number of DC vaccine induced LCMV gp33 specific CTLs and the lysis of relevant in vivo targets. However, the CTLA-4 blockage dependent expansion of CTLs also affect DC survival during booster DC injections and our data suggest that during a booster DC vaccine, the largest increase in CTL levels is already obtained during the first vaccination.

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

Dendritic Cell Immunotherapy, the Next Step in Cancer Treatment

Cancer immunotherapy has gained a lot of interest over the past few years due to the success of immune checkpoint inhibitors in treating cancer (1, 2). Immune checkpoint inhibitors, such as monoclonal antibodies against cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed death 1 (PD-1), have been shown to increase survival of patients with advanced cancers (1, 2). These in...

متن کامل

Dendritic Cell Immunotherapy, the Next Step in Cancer Treatment

Cancer immunotherapy has gained a lot of interest over the past few years due to the success of immune checkpoint inhibitors in treating cancer (1, 2). Immune checkpoint inhibitors, such as monoclonal antibodies against cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed death 1 (PD-1), have been shown to increase survival of patients with advanced cancers (1, 2). These in...

متن کامل

A Shot at Dendritic Cell-Based Vaccine Strategy against HIV-1

Introduction: Despite considerable efforts to control AIDS pandemic, it is still one of the significant infectious concerns worldwide. The advance in medical research has led to the development of highly active antiretroviral therapy with a considerable effect to suppress the disease. However, an effective vaccine capable of eradication the HIV pandemic is not available yet. Failure to develop ...

متن کامل

How do I steer this thing? Using dendritic cell targeted vaccination to more effectively guide the antitumor immune response with combination immunotherapy

Mounting an immune response sufficient to eradicate a tumor is the goal of modern immunotherapy. Single agent therapies with checkpoint inhibitors or costimulatory molecule agonists are effective only for a small portion of all treated patients. Combined therapy, e.g., CTLA-4 and PD-1 checkpoint blockade, is a more effective treatment modality, but in preclinical studies OX40 agonism with CTLA-...

متن کامل

Effect of LIGHT Adjuvant on Kinetics of T-Cell Responses Induced by HSV-1 DNA Immunization

Background: Studies on efficacy of various vaccines that prevent or reduce the primary and recurrent HSV-1 infection have demonstrated the importance of cellular immunity for protection against the infection. We previously used DNA vaccination to induce cellular immunity against HSV-1 infection in mice. Objective: The aim of our study was to evaluate the effect of LIGHT, a member of TNF super f...

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 Immune Based Therapies and Vaccines

دوره 5  شماره 

صفحات  -

تاریخ انتشار 2007