Phase I/II Study of Immunization With Multiple Peptides Mixed With the Immunological Montanide ISA 51 in HLA-A2 Patients With Metastatic Cutaneous Melanoma
Patients will receive six sequential immunizations with 8 peptides presented by HLA-A2 and
mixed with Montanide, at 2-week intervals. The 8 peptides will be injected at 8 distinct
injection sites. These peptides are the following: MAGE-1.A2, MAGE-3.A2, MAGE-4.A2,
MAGE-10.A2, MAGE-C2.A2 (ALKD), and NA17.A2 (20% intradermally and 80% subcutaneously);
NY-ESO-1.A2 and Tyrosinase.A2 (100% subcutaneously).
300 µg of each peptide will be mixed with 0.5ml of Montanide.
Tumor staging will be performed before inclusion and at week 13. PBL collections will be
performed before starting the treatment, and at weeks 3, 7 and 13. They will provide the T
lymphocytes for the immunological analysis.
At week 13, the PCR results of the pre-immune tumor biopsy must be available. Additional
cycles of immunization, ONLY with the peptides expressed by the tumor, mixed with Montanide,
will be proposed to patients without tumor progression requiring another treatment. A second
cycle of 3 injections at 6-week intervals will be started at week 17, followed by a third
cycle of 12 injections at 3-month intervals, starting at month 11. At any time, progression
of the disease necessitating any treatment not allowed during the study, will result in
The immune response may well be a limiting factor to the therapeutic efficacy of the
vaccine. If this is the case, it then becomes crucial to understand why some patients
develop a cytolytic T lymphocyte (CTL) response against the vaccine, while the majority of
them does not so. One possible explanation for the low frequency of clinical responses is
that each injection of a single peptide has a low probability to provide the adequate
stimulus to activate very rare CTL precursors. This probability should be increased if
several peptides known to be undoubtedly associated with tumor regressions were used
together to immunize patients.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
- To describe the CTL response to individual peptides after immunization with a combination of 8 peptides and Montanide ISA-51.
Nicolas VanBaren, MD
Ludwig Institute for Cancer Research
Belgium: Ministry of Social Affairs, Public Health and the Environment