Format

Send to

Choose Destination
Cancer Res. 2017 Apr 15;77(8):1918-1926. doi: 10.1158/0008-5472.CAN-16-2089. Epub 2017 Feb 15.

CD40 Signaling Drives Potent Cellular Immune Responses in Heterologous Cancer Vaccinations.

Author information

1
Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany.
2
Siriraj Hospital, Mahidol University, Bangkok, Thailand.
3
Institute of Transplant Immunology, IFB-Tx, Hannover Medical School Hannover, Hannover, Germany.
4
DZIF, German Center for Infectious Diseases, Hannover/Braunschweig, Germany.
5
Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany. Wirth.Thomas@mh-hannover.de.

Abstract

Antagonistic antibodies targeting coinhibitory receptors have revolutionized the treatment of cancer by inducing durable immune responses and clinical remissions in patients. In contrast, success of agonistic costimulatory antibodies has thus far been limited because of the insufficient induction of adaptive immune responses. Here, we describe a novel vaccination method consisting of a primary dendritic cell (DC) immunization followed by a composite vaccination, including an agonistic CD40 antibody, soluble antigen, and a TLR3 agonist, referred to as CoAT. In mice, DC/CoAT prime-boost vaccinations targeting either MHC class I or II neoantigens or tumor-associated antigens rendered up to 60% of the total T-cell population specific for a single tumor epitope. DC/CoAT induced durable and complete remissions of large subcutaneous tumors without detectable side effects. Thus, booster vaccinations with agonistic costimulatory antibodies represent an ideal means to amplify DC vaccinations and induce robust T-cell immune responses while providing maximum flexibility regarding the choice of antigen. Cancer Res; 77(8); 1918-26. ©2017 AACR.

PMID:
28202532
DOI:
10.1158/0008-5472.CAN-16-2089
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center