Immunologic responses to xenogeneic tyrosinase DNA vaccine administered by electroporation in patients with malignant melanoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-12

AUTHORS

Jianda Yuan, Geoffrey Y Ku, Matthew Adamow, Zhenyu Mu, Sapna Tandon, Drew Hannaman, Paul Chapman, Gary Schwartz, Richard Carvajal, Katherine S Panageas, Alan N Houghton, Jedd D Wolchok

ABSTRACT

BACKGROUND: Prior studies show that intramuscular injection and particle-mediated epidermal delivery of xenogeneic melanosomal antigens (tyrosinase or Tyr, gp100) induce CD8(+) T cell responses to the syngeneic protein. To further define the optimal vaccination strategy, we conducted a phase I study of in vivo electroporation (EP) of a murine Tyr DNA vaccine (pINGmuTyr) in malignant melanoma patients. METHODS: Human leukocyte antigen (HLA)-A1, A2, A24 or B35 stage IIb-IV melanoma patients received up to five doses of the mouse tyrosinase DNA vaccine by EP every three weeks at dose levels of 0.2 mg, 0.5 mg, or 1.5 mg per injection. Peripheral blood mononuclear cells (PBMC) were collected, cultured with a peptide pool containing eight HLA class I-restricted Tyr-specific T-cell epitopes, and analyzed by HLA-A*0101-restricted tetramers and intracellular cytokine staining (ICS). RESULTS: Twenty-four patients received ≥1 dose of the pINGmuTyr vaccine; PBMCs from 21 patients who completed all five doses were available for Tyr immune assays. The only common toxicity was grade 1 injection site reaction. Six of 15 patients (40%) in the 1.5 mg dose cohort developed Tyr-reactive CD8(+) T cell responses following stimulation, defined as a ≥3 standard deviation increase in baseline reactivity by tetramer or ICS assays. No Tyr-reactive CD8(+) T cell response was detected in the 0.2 mg and 0.5 mg dose cohort patients. Epitope spreading of CD8(+) T cell response to NY-ESO-1 was observed in one patient with vitiligo. One patient subsequently received ipilimumab and developed an enhanced Tyr-reactive response with polyfunctional cytokine profile. After a median follow-up of 40.9 months, median survival has not been reached. CONCLUSIONS: A regimen of five immunizations with pINGmuTyr administered by EP was found to be safe and resulted in Tyr-reactive immune responses in six of 15 patients at 1.5 mg dose cohort. TRIAL REGISTRATION: ClinicalTrials.gov NCT00471133. More... »

PAGES

20

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/2051-1426-1-20

DOI

http://dx.doi.org/10.1186/2051-1426-1-20

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1035943441

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24829756


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1186/2051-1426-1-20'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/2051-1426-1-20'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/2051-1426-1-20'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/2051-1426-1-20'


 

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