Effective melanoma immunotherapy in mice by the skin-depigmenting agent monobenzone and the adjuvants imiquimod and CpG.
BACKGROUND
Presently melanoma still lacks adequate treatment options for metastatic disease. While melanoma is exceptionally challenging to standard regimens, it is suited for treatment with immunotherapy based on its immunogenicity. Since treatment-related skin depigmentation is considered a favourable prognostic sign during melanoma intervention, we here aimed at the reverse approach of directly inducing vitiligo as a shortcut to effective anti-melanoma immunity.


RESULTS
We developed an effective and simple to use form of immunotherapy by combining the topical skin-bleaching agent monobenzone with immune-stimulatory imiquimod cream and cytosine-guanine oligodeoxynucleotides (CpG) injections (MIC therapy). This powerful new approach promptly induced a melanoma antigen-specific immune response, which abolished subcutaneous B16.F10 melanoma growth in up to 85% of C57BL/6 mice. Importantly, this regimen induced over 100 days of tumor-free survival in up to 60% of the mice, and forcefully suppressed tumor growth upon re-challenge either 65- or 165 days after MIC treatment cessation.


CONCLUSIONS
MIC therapy is effective in eradicating melanoma, by vigilantly incorporating NK-, B- and T cells in its therapeutic effect. Based on these results, the MIC regimen presents a high-yield, low-cost and simple therapy, readily applicable in the clinic.
van den Boorn
Jasper G
JG
Department of Dermatology and the Netherlands Institute for Pigment Disorders, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Konijnenberg
Debby
D
Tjin
Esther P M
EP
Picavet
Daisy I
DI
Meeuwenoord
Nico J
NJ
Filippov
Dmitri V
DV
van der Veen
J P Wietze
JP
Bos
Jan D
JD
Melief
Cornelis J M
CJ
Luiten
Rosalie M
RM
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000634:Aminoquinolines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D015226:Dinucleoside Phosphates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006873:Hydroquinones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000077271:Imiquimod; D007074:Immunoglobulin G / Q000276:immunology; D007167:Immunotherapy; D007279:Injections, Subcutaneous; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000187:drug effects; D008212:Lymphocyte Depletion; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010858:Pigmentation / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology
D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D015226:Dinucleoside Phosphates; D006873:Hydroquinones; D000077271:Imiquimod; D007074:Immunoglobulin G; C015772:CpG dinucleotide; C006429:monobenzone