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Peptide Vaccination Associated With Tumoral Immunomodulation in Patients With Advanced Metastatic Melanoma

NCT01191034 · Status: TERMINATED · Phase: PHASE1/PHASE2 · Type: INTERVENTIONAL · Enrollment: 2

Last updated 2019-03-12

No results posted yet for this study

Summary

Human cancers express tumor antigens that can be targeted by cytolytic T lymphocytes (CTL). These antigens consist of a small peptide, derived from endogenous proteins, that is presented at the cancer cell's surface by an HLA class I molecule. Such antigenic peptides, including MAGE-3.A1 and NA17.A2, have been tested in experimental therapeutic vaccines to elicit CTL responses in cancer patients, mainly with metastatic melanoma. Up to now, only rare tumor responses have been observed.

Tumor resistance to CTL killing is the most likely explanation for the poor effectiveness of cancer vaccines. This resistance is probably acquired by the tumor during its development and selected by its repetitive challenge with spontaneous anti-tumoral immune responses. The precise molecular mechanisms of tumor resistance remain unknown. The observation that tumor-infiltrating lymphocytes (TIL) purified from melanoma metastases can recognize and kill autologous tumor cells in vitro, whilst they seem unable to control tumor growth in vivo, suggests that this resistance is hosted by the tumor environment, rather than being the result of a generalized immune suppression.

The investigators have developed a murine model of cutaneous graft rejection that mimics the situation in melanoma. Female CBA mice do not reject syngeneic male skin grafts, even though they mount a spontaneous CTL response against H-Y, a male specific minor histocompatibility antigen, following grafting. The investigators have tested various experimental procedures aimed at inducing effective graft rejection in these mice. This was obtained with a combination of IFN-α, IL-2, GM-CSF, each administered separately under the skin graft, associated with topical applications of imiquimod. All these agents are available as registered drugs. Based on this murine model of cutaneous allograft rejection, the investigators postulate that local immunomodulation with this combination can trigger an effective tumor rejection process, and induce a more efficient and long-lasting anti-tumoral immune response following peptide vaccination.

Conditions

Interventions

DRUG

Vaccine MAGE-3.A1 peptide, or the NA17.A2 peptide + IL-2, IFN-α and GMCSF, Imiquimod.

The vaccine will be either the MAGE-3.A1 peptide, or the NA17.A2 peptide, or both,matching the patient's HLA type and the gene expression of his tumor. If both antigens are expressed, then the patient will receive both peptides. This treatment will combine subcutaneous peritumoral injections of IL-2, IFN-α and GMCSF,as well as topical applications of imiquimod.

Sponsors & Collaborators

  • Cliniques universitaires Saint-Luc- Université Catholique de Louvain

    lead OTHER

Principal Investigators

  • Baurain Jean-Francois, MD, PhD · Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2010-08-31
Primary Completion
2012-08-31
Completion
2012-08-01

Countries

  • Belgium

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT01191034 on ClinicalTrials.gov