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Erschienen in:
01.01.2016 | Original Article
A randomized pilot trial testing the safety and immunologic effects of a MAGE-A3 protein plus AS15 immunostimulant administered into muscle or into dermal/subcutaneous sites
Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 1/2016
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Introduction
Methods to induce T cell responses to protein vaccines have not been optimized. The immunostimulant AS15 has been administered with the recombinant MAGE-A3 protein (recMAGE-A3) i.m. but not i.d. or s.c. This study tests hypotheses that the i.d./s.c. route is safe and will increase CD4+ and CD8+ T cell responses to MAGE-A3.
Patients and methods
Twenty-five patients with resected stage IIB-IV MAGE-A3+ melanoma were randomized to immunization with recMAGE-A3 combined with AS15 immunostimulant (MAGE-A3 immunotherapeutic) either i.m. (group A, n = 13) or i.d./s.c. (group B, n = 12). Adverse events were recorded. Ab responses to MAGE-A3 were measured by ELISA. T cell responses to overlapping MAGE-A3 peptides were assessed in PBMC and a sentinel immunized node (SIN) after 1 in vitro stimulation with recMAGE-A3, by IFN-γ ELISPOT assay and by flow cytometry for multifunctional (TNF-α/IFN-γ) responses.
Results
Both routes of immunization were well tolerated without treatment-related grade 3 adverse events. All patients had durable Ab responses. For all 25 patients, the T cell response rate by ELISPOT assay was 30 % in SIN (7/23) but only 4 % (1/25) in PBMC. By flow cytometry, multifunctional CD8+ T cell responses were identified in one patient in each group; multifunctional CD4+ T cell response rates for groups A and B, respectively, were 31 and 64 % in SIN and 31 and 50 % in PBMC.
Conclusion
The MAGE-A3 immunotherapeutic was well tolerated after i.d./s.c. administration, with trends to higher CD4+ T cell response rates than with i.m. administration. This study supports further study of AS15 by i.d./s.c. administration.