Immunostimulatory cancer chemotherapy using local ingenol-3-angelate and synergy with immunotherapies.
Ingenol-3-angelate is a new local chemotherapeutic agent in clinical trails that induces primary necrosis of tumour cells and transient local inflammation. Here we show that cure of subcutaneous tumours with ingenol-3-angelate (PEP005) resulted in the generation of anti-cancer CD8 T cells that could regress metastases. Furthermore, PEP005-mediated cure synergized with several CD8 T cell-based immunotherapies to regress further distant metastases. PEP005 was shown to have adjuvant properties, being able to upregulate CD80 and CD86 expression on dendritic cells in vivo, and to promote CD8 T cell induction when co-delivered with a protein antigen. PEP005 thus emerges as a unique local chemotherapeutic immunostimulatory debulking agent that could be used in conjunction with immunotherapies to promote regression of metastases.
Le
Thuy T T
TT
Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Brisbane, Queensland, Australia.
Gardner
Joy
J
Hoang-Le
Diem
D
Schmidt
Chris W
CW
MacDonald
Kelli P
KP
Lambley
Eleanore
E
Schroder
Wayne A
WA
Ogbourne
Steven M
SM
Suhrbier
Andreas
A
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000276:immunology; D018929:Cell Culture Techniques; D002645:Chickens; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004224:Diterpenes / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007114:Immunization / Q000379:methods*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000556:secondary; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000276:immunology; D051379:Mice; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
C486592:3-ingenyl angelate; D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D004224:Diterpenes