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 IFNγ ELISPOT assay and by flow cytometry for multifunctional (TNFα/IFNγ) 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 1 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.