Back to Search
Start Over
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.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2016 Mar 15; Vol. 22 (6), pp. 1330-40. Date of Electronic Publication: 2015 Oct 23. - Publication Year :
- 2016
-
Abstract
- 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.<br />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.<br />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.<br />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.<br /> (©2015 American Association for Cancer Research.)
- Subjects :
- Antigens, CD chemistry
Antigens, Neoplasm immunology
Biomarkers
CD4-Positive T-Lymphocytes metabolism
CD8-Positive T-Lymphocytes metabolism
Cancer Vaccines administration & dosage
Cancer Vaccines adverse effects
Combined Modality Therapy
Female
Humans
Lymphocyte Count
MART-1 Antigen immunology
Male
Melanoma pathology
Treatment Outcome
Vaccination
Lymphocyte Activation Gene 3 Protein
Antigens, CD immunology
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes immunology
Cancer Vaccines immunology
Melanoma immunology
Melanoma therapy
Peptides immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 22
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 26500235
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-15-1212