Document Detail


Phase I trial of OTS11101, an anti-angiogenic vaccine targeting Vascular Endothelial Growth Factor Receptor 1 in solid tumor.
MedLine Citation:
PMID:  23020774     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OTS11101 is a novel peptide vaccine that acts as an angiogenesis inhibitor by inducing cytotoxic T lymphocyte (CTL) cells that specifically target vascular endothelial cells expressing vascular endothelial growth factor (VEGF) receptor 1. We conducted a phase I study to evaluate the safety, tolerability, maximum tolerated dose, and pharmacodynamic biomarker status of this vaccine. Nine patients with advanced solid tumors received 1.0 mg, 2.0 mg, or 3.0 mg of OTS11101 subcutaneously, once a week in a 28-day cycle. Three patients experienced grade 1 injection site reactions, which were the most frequent adverse events. Grade 2 proteinuria and hypertension each occurred in one patient. As other toxicities were generally mild, the maximum tolerated dose was not reached. Furthermore, we explored the induction of specific activated CTLs, and biomarkers related to angiogenesis. A pharmacodynamics study revealed that induction of specific CTLs was observed for a dose of 2.0 and 3.0 mg. The serum concentrations of soluble VEGF receptor 1 and 2 after vaccination increased significantly compared with baseline. A microarray was performed to give a comprehensive analysis of gene expression, suggesting that OTS11101 vaccination resulted in T cell activation in a clinical setting. In conclusion, OTS11101 was well tolerated in patients up to 3.0 mg once weekly and our biomarker analysis suggested that this anti-angiogenesis vaccine is biologically active.
Authors:
Hidetoshi Hayashi; Takayasu Kurata; Yasuhito Fujisaka; Hisato Kawakami; Kaoru Tanaka; Takafumi Okabe; Masayuki Takeda; Taroh Satoh; Koji Yoshida; Takuya Tsunoda; Tokuzo Arao; Kazuto Nishio; Kazuhiko Nakagawa
Related Documents :
12836644 - Improving influenza vaccination rates in the elderly.
7735634 - Sense and nonsense of influenza vaccination in asthma and chronic obstructive pulmonary...
19481314 - Knowledge, attitudes and vaccination coverage of healthcare workers regarding occupatio...
15313884 - Effect of influenza vaccination on excess deaths occurring during periods of high circu...
7567714 - Vaccination update. diphtheria, tetanus, pertussis, mumps, rubella, measles.
15210954 - Poly-beta amino ester-containing microparticles enhance the activity of nonviral geneti...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-29
Journal Detail:
Title:  Cancer science     Volume:  -     ISSN:  1349-7006     ISO Abbreviation:  Cancer Sci.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-10-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101168776     Medline TA:  Cancer Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 Japanese Cancer Association.
Affiliation:
Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka, 589-8511, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Social cognition in bipolar disorder versus schizophrenia: comparability in mental state decoding de...
Next Document:  Robust Gaussian graphical modeling via l1 penalization.