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| Status |
Public on Apr 01, 2017 |
| Title |
Vaccination and topical imiquimod treatment promote immune signatures in melanoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Introduction: Infiltration of cancers by T-cells is associated with improved patient survival and response to immune therapies; however, optimal approaches to induce T-cell infiltration of tumors are not known. This study tests the hypothesis that topical treatment of melanoma metastases with the TLR7 agonist imiquimod treatment plus administration of a multipeptide cancer vaccine will improve immune cell infiltration of melanoma metastases. Patients and Methods: Eligible patients were immunized with a vaccine comprised of 12 melanoma peptides and a tetanus toxoid-derived helper peptide, and imiquimod was applied topically to tumors daily. Adverse events (AE; CTCAE v4.03) were recorded and effects on the tumor microenvironment (TME) were evaluated from sequential tumor biopsies. T-cell responses were assessed by IFNgamma ELIspot assay, and T-cell tetramer staining. Patient tumors were evaluated for immune cell infiltration, cytokine and chemokine production, and gene expression. Results and Conclusions: Four eligible patients were enrolled, and administration of imiquimod and vaccination was well tolerated in these patients. Circulating T-cell responses to the vaccine were detected by ex vivo ELIspot assay in 3 of 4 patients. Treatment of metastases with imiquimod induced immune cell infiltration and favorable gene signatures in the patients with circulating T-cell responses. This study supports further study of topical imiquimod combined with vaccines or other immune therapies for the treatment of melanoma. Precis: This clinical trial tested topical application of imiquimod to melanoma metastases combined with a melanoma vaccine. The regimen dramatically upregulated immune rejection gene signatures in melanoma metastases and increased T-cell infiltrate.
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| Overall design |
Biopsies (incisional, core or excisional biopsies) of cutaneous or subcutaneous metastatic melanoma were obtained on day 1 (baseline, pre-treatment) (n=3), day 22 (after 3 weeks of imiquimod treatment, and 1 week after the third vaccine) (n=5) and day 43 (after 6 weeks of imiquimod, and 1 week after the 4th vaccine) (n=3).
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| Citation(s) |
27522582 |
| |
| Submission date |
Apr 07, 2016 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Francesco Maria Marincola |
| E-mail(s) |
fmarincola@sidra.org
|
| Phone |
301-793-8210
|
| Organization name |
Sidra Medical and Research Center
|
| Street address |
Al Nasr Tower, AL Corniche Street, PO Box 26999
|
| City |
Doha |
| ZIP/Postal code |
PO Box 26999 |
| Country |
Qatar |
| |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
|
| Samples (11)
|
| GSM2111296 |
Patient 1 - Pre-treatment Biopsy - Day 1 - mAdbID:120025 |
| GSM2111297 |
Patient 1 - Biopsy with Imiquimod and IFNgamma - Day 22 - mAdbID:120026 |
| GSM2111298 |
Patient 1 - Biopsy with Imiquimod and IFNgamma - Day 43 - mAdbID:120027 |
| GSM2111299 |
Patient 2 - Pre-treatment Biopsy - Day 1 - mAdbID:120028 |
| GSM2111300 |
Patient 2 - Biopsy with Imiquimod and IFNgamma - Day 22 - repeat 1 - mAdbID:120029 |
| GSM2111301 |
Patient 2 - Biopsy with Imiquimod and IFNgamma - Day 22 - repeat 2 - mAdbID:120030 |
| GSM2111302 |
Patient 3 - Pre-treatment Biopsy - Day 1 - mAdbID:120031 |
| GSM2111303 |
Patient 3 - Biopsy with Imiquimod and IFNgamma - Day 22 - repeat 1 - mAdbID:120032 |
| GSM2111304 |
Patient 3 - Biopsy with Imiquimod and IFNgamma - Day 22 - repeat 2 - mAdbID:120033 |
| GSM2111305 |
Patient 3 - Biopsy with Imiquimod and IFNgamma - Day 43 - repeat 1 - mAdbID:120034 |
| GSM2111306 |
Patient 3 - Biopsy with Imiquimod and IFNgamma - Day 43 - repeat 2 - mAdbID:120035 |
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| Relations |
| BioProject |
PRJNA317666 |
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