TY - JOUR
T1 - CD40 stimulation leads to effective therapy of CD40- tumors through induction of strong systemic cytotoxic T lymphocyte immunity
AU - van Mierlo, Geertje J. D.
AU - Boer, Annemieke Th. Den
AU - Medema, Jan Paul
AU - van der Voort, Ellen I. H.
AU - Fransen, Marieke F.
AU - Offringa, Rienk
AU - Melief, Cornelis J. M.
AU - Toes, Rene E. M.
PY - 2002
Y1 - 2002
N2 - Adequate spontaneous activation of tumor-specific T lymphocytes in tumor-bearing hosts is rare, despite the expression of tumor antigens that are potentially highly immunogenic. For example, failure of the immune system to raise competent responses against established tumors expressing the human adenovirus E1A-antigen allows this tumor to grow in immunocompetent mice. We show that systemic in vivo administration of agonistic anti-CD40 anti- bodies into tumor-bearing mice results in tumor eradication mediated by CD8+ T cells. Treatment resulted in a strong expansion and systemic accumulation of E1A-specific CTL and depended on CD40 expression on host cells, as the tumor was CD40-, and therapy failed in CD40-deficient mice. Local intratumoral administration of anti-CD40 mAb is equally effective in licensing strong, systemic CTL immunity, resulting in the clearance of distant tumor nodules. Our data indicate that the immune response after cancer-host interactions can be directed toward competence, leading to the cure of established tumors merely by delivery of a CD40-dependent "license to kill" signal.
AB - Adequate spontaneous activation of tumor-specific T lymphocytes in tumor-bearing hosts is rare, despite the expression of tumor antigens that are potentially highly immunogenic. For example, failure of the immune system to raise competent responses against established tumors expressing the human adenovirus E1A-antigen allows this tumor to grow in immunocompetent mice. We show that systemic in vivo administration of agonistic anti-CD40 anti- bodies into tumor-bearing mice results in tumor eradication mediated by CD8+ T cells. Treatment resulted in a strong expansion and systemic accumulation of E1A-specific CTL and depended on CD40 expression on host cells, as the tumor was CD40-, and therapy failed in CD40-deficient mice. Local intratumoral administration of anti-CD40 mAb is equally effective in licensing strong, systemic CTL immunity, resulting in the clearance of distant tumor nodules. Our data indicate that the immune response after cancer-host interactions can be directed toward competence, leading to the cure of established tumors merely by delivery of a CD40-dependent "license to kill" signal.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=0037117542&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/11929985
U2 - https://doi.org/10.1073/pnas.082107699
DO - https://doi.org/10.1073/pnas.082107699
M3 - Article
C2 - 11929985
SN - 0027-8424
VL - 99
SP - 5561
EP - 5566
JO - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
JF - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
IS - 8
ER -