A Phase I Study of Telomerase-specific Replication Competent Oncolytic Adenovirus (Telomelysin) for Various Solid Tumors
作者： John Nemunaitis , Alex W Tong , Michael Nemunaitis , Neil Senzer , Anagha P Phadke
DOI: 10.1038/MT.2009.262
关键词: Telomerase 、 Immunology 、 Cancer research 、 Response Evaluation Criteria in Solid Tumors 、 Adenoviridae 、 Oncolytic adenovirus 、 Telomerase reverse transcriptase 、 Chills 、 Oncolytic virus 、 Medicine 、 Viral replication
摘要: A phase I clinical trial was conducted to determine the safety of Telomelysin, a human telomerase reverse transcriptase (hTERT) promoter driven modified oncolytic adenovirus, in patients with advanced solid tumors. single intratumoral injection (IT) Telomelysin administered three cohorts (1 × 1010, 1 1011, 1012 viral particles). Safety, response and pharmacodynamics were evaluated. Sixteen variety tumors enrolled. IT well tolerated at all dose levels. Common grade 2 toxicities included site reactions (pain, induration) systemic (fever, chills). hTERT expression demonstrated biopsy 9 12 patients. Viral DNA transiently detected plasma 13 16 detectable four or sputum day 7 14 post-treatment despite below levels 24 h, suggesting replication. One patient had partial injected malignant lesion. Seven fulfilled Response Evaluation Criteria Solid Tumors (RECIST) definition for stable disease 56 after treatment. tolerated. Evidence antitumor activity suggested.
nature.com
elsevier.com
sci-hub.se 参考文章(50)
M. S. Horwitz, J. Tufariello, A. Grunhaus, G. Fejer, Model Systems for Studying the Effects of Adenovirus E3 Genes on Virulence In Vivo Current Topics in Microbiology and Immunology. ,vol. 199, pp. 195- 211 ,(1995) , 10.1007/978-3-642-79586-2_10
Richard G. Vile, Ian R. Hart, In Vitro and in Vivo Targeting of Gene Expression to Melanoma Cells Cancer Research. ,vol. 53, pp. 962- 967 ,(1993)
A. M. DeMarzo, T. L. DeWeese, B. Mikhak, M. Goemann, Ronald Rodriguez, W. G. Nelson, R. DeJong, J. W. Simons, M. A. Carducci, D. C. Yu, R. Drew, Y. Chen, U. Hamper, S. Piantadosi, H. Van der Poel, S. Li, N. Detorie, D. R. Henderson, T. Haulk, A phase I trial of CV706, a replication-competent, PSA selective oncolytic adenovirus, for the treatment of locally recurrent prostate cancer following radiation therapy. Cancer Research. ,vol. 61, pp. 7464- 7472 ,(2001)
D. Feuerbach, H.G. Burgert, Novel proteins associated with MHC class I antigens in cells expressing the adenovirus protein E3/19K. The EMBO Journal. ,vol. 12, pp. 3153- 3161 ,(1993) , 10.1002/J.1460-2075.1993.TB05984.X
William S.M. Wold, Linda R. Gooding, Region E3 of adenovirus: a cassette of genes involved in host immunosurveillance and virus-cell interactions. Virology. ,vol. 184, pp. 1- 8 ,(1991) , 10.1016/0042-6822(91)90815-S
Drew L Lichtenstein, William S M Wold, Experimental infections of humans with wild-type adenoviruses and with replication-competent adenovirus vectors: replication, safety, and transmission. Cancer Gene Therapy. ,vol. 11, pp. 819- 829 ,(2004) , 10.1038/SJ.CGT.7700765
Qiuwei Pan, Bisheng Liu, Jin Liu, Rong Cai, Yigang Wang, Cheng Qian, Synergistic induction of tumor cell death by combining cisplatin with an oncolytic adenovirus carrying TRAIL. Molecular and Cellular Biochemistry. ,vol. 304, pp. 315- 323 ,(2007) , 10.1007/S11010-007-9514-6
Koji Kawakami, Fumihiko Takeshita, Raj K. Puri, Identification of Distinct Roles for a Dileucine and a Tyrosine Internalization Motif in the Interleukin (IL)-13 Binding Component IL-13 Receptor α2 Chain Journal of Biological Chemistry. ,vol. 276, pp. 25114- 25120 ,(2001) , 10.1074/JBC.M100936200
E Galanis, S H Okuno, A G Nascimento, B D Lewis, R A Lee, A M Oliveira, J A Sloan, P Atherton, J H Edmonson, C Erlichman, B Randlev, Q Wang, S Freeman, J Rubin, Phase I–II trial of ONYX-015 in combination with MAP chemotherapy in patients with advanced sarcomas Gene Therapy. ,vol. 12, pp. 437- 445 ,(2005) , 10.1038/SJ.GT.3302436
Yu-An Zhang, John Nemunaitis, Shirley K. Samuel, Patrick Chen, Yuqiao Shen, Alex W. Tong, Antitumor Activity of an Oncolytic Adenovirus-Delivered Oncogene Small Interfering RNA Cancer Research. ,vol. 66, pp. 9736- 9743 ,(2006) , 10.1158/0008-5472.CAN-06-1617