In vivo administration of artificial antigen-presenting cells activates low-avidity T cells for treatment of cancer.

نویسندگان

  • Stefano Ugel
  • Alessia Zoso
  • Carmela De Santo
  • Yu Li
  • Ilaria Marigo
  • Paola Zanovello
  • Elisa Scarselli
  • Barbara Cipriani
  • Mathias Oelke
  • Jonathan P Schneck
  • Vincenzo Bronte
چکیده

The development of effective antitumor immune responses is normally constrained by low-avidity, tumor-specific CTLs that are unable to eradicate the tumor. Strategies to rescue antitumor activity of low-avidity melanoma-specific CTLs in vivo may improve immunotherapy efficacy. To boost the in vivo effectiveness of low-avidity CTLs, we immunized mice bearing lung melanoma metastases with artificial antigen-presenting cells (aAPC), made by covalently coupling (pep)MHC-Ig dimers and B7.1-Ig molecules to magnetic beads. aAPC treatment induced significant tumor reduction in a mouse telomerase antigen system, and complete tumor eradication in a mouse TRP-2 antigen system, when low-avidity CTLs specific for these antigens were adoptively transferred. In addition, in an in vivo treatment model of subcutaneous melanoma, aAPC injection also augmented the activity of adoptively transferred CTLs and significantly delayed tumor growth. In vivo tumor clearance due to aAPC administration correlated with in situ proliferation of the transferred CTL. In vitro studies showed that aAPC effectively stimulated cytokine release, enhanced CTL-mediated lysis, and TCR downregulation in low-avidity CTLs. Therefore, in vivo aAPC administration represents a potentially novel approach to improve cancer immunotherapy.

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

Immunology In vivo Administration of Artificial Antigen-Presenting Cells Activates Low-Avidity T Cells for Treatment of Cancer

The development of effective antitumor immune responses is normally constrained by low-avidity, tumor-specific CTLs that are unable to eradicate the tumor. Strategies to rescue antitumor activity of low-avidity melanoma-specific CTLs in vivo may improve immunotherapy efficacy. To boost the in vivo effectiveness of low-avidity CTLs, we immunized mice bearing lung melanoma metastases with artific...

متن کامل

Dendritic Cells and Their Role in Cancer Immunotherapy

Dendritic cells (DCs) are antigen presenting cells with unique capability to take up and process antigens in the peripheral blood and tissues. They subsequently migrate to draining lymph nodes where they present these antigens and stimulate naive T lympho-cytes. During their life cycle, DCs go through two maturation stages and are referred to as immature and mature cells, respectively. While im...

متن کامل

Human Leukocyte Antigen-G Expression on Dendritic Cells Induced by Transforming Growth Factor-β1 and CD4+ T Cells Proliferation

Background: During antigen capture and processing, mature dendritic cells (DC) express large amounts of peptide-MHC complexes and accessory molecules on their surface. DC are antigen-presenting cells that have an important role in tolerance and autoimmunity. The transforming growth factor-beta1 (TGF-β1) cytokine has a regulatory role on the immune and non-immune cells. The aim of this study is ...

متن کامل

Mathematical Modeling of Cancer Cells and Chemotherapy Protocol Dealing Optimization Using Fuzzy Differential Equations And Lypunov Stability Criterion

Mathematical models can simulate the growth and proliferation of cells in the interaction with healthy cells, the immune system and measure the toxicity of drug and its effects on healthy tissue pay. One of the main goals of modeling the structure and growth of cancer cells is to find a control model suitable for administration among patients. In this study, a new mathematical model is designed...

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:
  • Cancer research

دوره 69 24  شماره 

صفحات  -

تاریخ انتشار 2009