Intratumoral poly-N-acetyl glucosamine-based polymer matrix provokes a prolonged local inflammatory response that, when combined with IL-2, induces regression of malignant mesothelioma in a murine model.
The authors have previously shown that cytokines delivered directly into malignant mesothelioma (MM) tumors can retard tumor growth and mediate tumor regression under certain conditions. In this report the authors compared the efficacy of serial intratumoral injections of three cytokines, GM-CSF, IL-12, and IL-2, to their sustained release using a single injection in a poly-N-acetyl glucosamine gel. IL-2 combined with the polymer gel gave optimal antitumor results when MM tumors were accessible as either subcutaneous deposits or as masses spread throughout the peritoneal cavity. The gel acted not only as a slow-release cytokine depot but also as a trigger for inflammation and recruited several immune cell types to the gel/tumor interface; when combined with IL-2 (but not with GM-CSF or IL-12), it acted as a selective reservoir for infiltrating CD8+ T cells. Hence, the IL-2/gel may provide a microenvironment that allows intratumoral T cells to proliferate and retain their cytolytic functions as they encounter their cognate antigens expressed by tumor cells.
van Bruggen
Ivonne
I
University of Western Australia, School of Medicine and Pharmacology, Perth, Western Australia 6009.
Nelson
Delia J
DJ
Currie
Andrew J
AJ
Jackaman
Connie
C
Robinson
Bruce W S
BW
D000117:Acetylglucosamine / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000008:administration & dosage* / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D018572:Disease-Free Survival; D005260:Female; D005782:Gels; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000737:chemistry; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D018664:Interleukin-12 / Q000008:administration & dosage / Q000737:chemistry; D007376:Interleukin-2 / Q000008:administration & dosage / Q000737:chemistry; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008654:Mesothelioma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology
D016207:Cytokines; D003692:Delayed-Action Preparations; D005782:Gels; D007376:Interleukin-2; C113831:poly-N-acetyl glucosamine; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000117:Acetylglucosamine