Journal
JOURNAL OF IMMUNOTHERAPY
Volume 32, Issue 5, Pages 498-507Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CJI.0b013e3181a00068
Keywords
melanoma; vaccination; mRNA vaccination; protamine-protected mRNA
Categories
Ask authors/readers for more resources
In mice, injection of messenger RNA (mRNA) coding for tumor-associate antigens can induce antitumor immune responses and therefore offers a broadly applicable immunotherapy approach. We injected intradermally protamine-stabilized mRNAs coding for Melan-A, Tyrosinase, gp100, Mage-A1, Mage-A3, and Survivin in 21 metastatic melanoma patients. In 10 patients keyhole limpet hemocyanin (KLH) was added to the vaccine. Granulocyte macrophage colony-stimulating factor was applied as an adjuvant. Endpoints were toxicity and immune responses. No adverse events more than grade 11 have been observed. During treatment the frequency of Foxp3+/CD4+ regulatory T cells was significantly decreased upon mRNA vaccination in peripheral blood of the patients in the KLH arm. whereas myeloid suppressor cells (CD11b+HLA-DR(lo) monocytes) were reduced in the patients not receiving KLH. A reproducible increase of vaccine-directed T cells was observed in 2 of 4 immunologically evaluable patients. One of 7 patients with measurable disease showed a complete response. In conclusion, we show here that direct injection of protamine-protected mRNA is feasible and safe. The significant influence of the treatment on the frequency of immunosuppressive cells, the increase of vaccine-directed T cells upon treatment in a Subset of patients together with the demonstration of a complete clinical response encourage further clinical investigation of the protamine-mRNA vaccine. This trial was registered at www.clinicaltrials.gov as #NCT00204607.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available