Glycolipid antigens for treating hepatic colorectal cancer metastases and their effect on the therapeutic efficacy of live attenuated Listeria monocytogenes.
Previous work demonstrated that a subset of natural killer T cells in mice decreased the antitumor efficacy of live attenuated Listeria monocytogenes where the actin A and internalin B genes were genetically deleted (LMD) against murine hepatic colorectal cancer metastases. Therefore, we hypothesized that the use of specific glycolipids known to selectively stimulate natural killer T-cell subsets used alone or co-administered with LMD would increase survival. We found that early or multiple administrations of glycolipids after tumor challenge had a strong impact on survival with or without LMD. Solitary administration or treatment given later was less efficacious but still showed a strong trend toward enhancing the antitumor activity of LMD. These results underscore the potential of glycolipids in the treatment of hepatic metastases and encourage further investigations into the immunomodulation of natural killer T cells to enhance the antitumor activity of LMD.
Department of Surgery, Johns Hopkins University, 600 N Wolfe St, Baltimore, MD 21287, USA. feisfeet@gmail.com
Kelly
K
Olino
Barish H
BH
Edil
Kristen F
KF
Meckel
Xiaoyu
X
Pan
Avesh
A
Thuluvath
Drew M
DM
Pardoll
Richard D
RD
Schulick
Kiyoshi
K
Yoshimura
Walter P
WP
Weber
D000818:Animals; D000941:Antigens / Q000627:therapeutic use*; D001691:Biological Therapy; D003131:Combined Modality Therapy; D005260:Female; D006017:Glycolipids / Q000276:immunology*; D008089:Listeria monocytogenes; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000628:therapy
D000941:Antigens; D006017:Glycolipids