Vaccination with LAG-3Ig (IMP321) and peptides induces specific CD4 and CD8 T-cell responses in metastatic melanoma patients - report of a phase I/IIa clinical trial.
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2016
- doi: 10.1158/1078-0432.CCR-15-1212
- issn: 1078-0432
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Communicable diseases--Vaccination Preventive inoculation Inoculation Preventive inoculation Diseases--VaccinationCiter ce document
A. Legat et al., « Vaccination with LAG-3Ig (IMP321) and peptides induces specific CD4 and CD8 T-cell responses in metastatic melanoma patients - report of a phase I/IIa clinical trial. », Serveur académique Lausannois, ID : 10.1158/1078-0432.CCR-15-1212
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PURPOSE: Cancer vaccines aim to generate and maintain antitumor immune responses. We designed a phase I/IIa clinical trial to test a vaccine formulation composed of Montanide ISA-51 (Incomplete Freund's Adjuvant), LAG-3Ig (IMP321, a non-Toll like Receptor agonist with adjuvant properties), and five synthetic peptides derived from tumor-associated antigens (four short 9/10-mers targeting CD8 T-cells, and one longer 15-mer targeting CD4 T-cells). Primary endpoints were safety and T-cell responses. EXPERIMENTAL DESIGN: Sixteen metastatic melanoma patients received serial vaccinations. Up to nine injections were subcutaneously administered in three cycles, each with three vaccinations every 3 weeks, with 6 to 14 weeks interval between cycles. Blood samples were collected at baseline, 1-week after the third, sixth and ninth vaccination, and 6 months after the last vaccination. Circulating T-cells were monitored by tetramer staining directly ex vivo, and by combinatorial tetramer and cytokine staining on in vitro stimulated cells. RESULTS: Side effects were mild to moderate, comparable to vaccines with Montanide alone. Specific CD8 T-cell responses to at least one peptide formulated in the vaccine preparation were found in 13 of 16 patients. However, two of the four short peptides of the vaccine formulation did not elicit CD8 T-cell responses. Specific CD4 T-cell responses were found in all 16 patients. CONCLUSIONS: We conclude that vaccination with IMP321 is a promising and safe strategy for inducing sustained immune responses, encouraging further development for cancer vaccines as components of combination therapies. Clin Cancer Res; 22(6); 1330-40. ©2015 AACR.