PURPOSE: Poxviral vectors have a proven safety record and can be used to incorporate multiple transgenes. Prior clinical trials with poxviral vaccines have shown that immunologic tolerance to self-antigens can be broken. Carcinoembryonic antigen (CEA) and MUC-1 are overexpressed in a substantial proportion of common solid carcinomas. The primary end point of this study was vaccine safety, with immunologic and clinical responses as secondary end points. EXPERIMENTAL DESIGN: We report here a pilot study of 25 patients treated with a poxviral vaccine regimen consisting of the genes for CEA and MUC-1, along with a triad of costimulatory molecules (TRICOM; composed of B7.1, intercellular adhesion molecule 1, and lymphocyte function-associated antigen 3) engineered into vaccinia (PANVAC-V) as a prime vaccination and into fowlpox (PANVAC-F) as a booster vaccination. RESULTS: The vaccine was well tolerated. Apart from injection-site reaction, no grade > or =2 toxicity was seen in more than 2% of the cycles. Immune responses to MUC-1 and/or CEA were seen following vaccination in 9 of 16 patients tested. A patient with clear cell ovarian cancer and symptomatic ascites had a durable (18-month) clinical response radiographically and biochemically, and one breast cancer patient had a confirmed decrease of >20% in the size of large liver metastasis. CONCLUSIONS: This vaccine strategy seems to be safe, is associated with both CD8 and CD4 immune responses, and has shown evidence of clinical activity. Further trials with this agent, either alone or in combination with immunopotentiating and other therapeutic agents, are warranted.
PURPOSE: Poxviral vectors have a proven safety record and can be used to incorporate multiple transgenes. Prior clinical trials with poxviral vaccines have shown that immunologic tolerance to self-antigens can be broken. Carcinoembryonic antigen (CEA) and MUC-1 are overexpressed in a substantial proportion of common solid carcinomas. The primary end point of this study was vaccine safety, with immunologic and clinical responses as secondary end points. EXPERIMENTAL DESIGN: We report here a pilot study of 25 patients treated with a poxviral vaccine regimen consisting of the genes for CEA and MUC-1, along with a triad of costimulatory molecules (TRICOM; composed of B7.1, intercellular adhesion molecule 1, and lymphocyte function-associated antigen 3) engineered into vaccinia (PANVAC-V) as a prime vaccination and into fowlpox (PANVAC-F) as a booster vaccination. RESULTS: The vaccine was well tolerated. Apart from injection-site reaction, no grade > or =2 toxicity was seen in more than 2% of the cycles. Immune responses to MUC-1 and/or CEA were seen following vaccination in 9 of 16 patients tested. A patient with clear cell ovarian cancer and symptomatic ascites had a durable (18-month) clinical response radiographically and biochemically, and one breast cancerpatient had a confirmed decrease of >20% in the size of large liver metastasis. CONCLUSIONS: This vaccine strategy seems to be safe, is associated with both CD8 and CD4 immune responses, and has shown evidence of clinical activity. Further trials with this agent, either alone or in combination with immunopotentiating and other therapeutic agents, are warranted.
Authors: John L Marshall; James L Gulley; Philip M Arlen; Patricia K Beetham; Kwong-Yok Tsang; Rebecca Slack; James W Hodge; Sandra Doren; Douglas W Grosenbach; Jimmy Hwang; Evelyn Fox; Lauretta Odogwu; Susie Park; Dennis Panicali; Jeffrey Schlom Journal: J Clin Oncol Date: 2004-12-21 Impact factor: 44.544
Authors: John G Gribben; David P Ryan; Richard Boyajian; Robert G Urban; Mary L Hedley; Kathleen Beach; Patrick Nealon; Ursula Matulonis; Susana Campos; Timothy D Gilligan; Paul G Richardson; Blossom Marshall; Donna Neuberg; Lee M Nadler Journal: Clin Cancer Res Date: 2005-06-15 Impact factor: 12.531
Authors: M E Christine Lutsiak; Roshanak T Semnani; Roberto De Pascalis; Syed V S Kashmiri; Jeffrey Schlom; Helen Sabzevari Journal: Blood Date: 2004-12-09 Impact factor: 22.113
Authors: Charlie T Garnett; Claudia Palena; Mala Chakraborty; Mala Chakarborty; Kwong-Yok Tsang; Jeffrey Schlom; James W Hodge Journal: Cancer Res Date: 2004-11-01 Impact factor: 12.701
Authors: Ramesh K Ramanathan; Kenneth M Lee; John McKolanis; Elizabeth Hitbold; Wolfgang Schraut; Arthur J Moser; Elizabeth Warnick; Theresa Whiteside; Jennifer Osborne; Hyoung Kim; Roger Day; Monica Troetschel; Olivera J Finn Journal: Cancer Immunol Immunother Date: 2004-09-14 Impact factor: 6.968
Authors: Bruce E Loveland; Anne Zhao; Shane White; Hui Gan; Kate Hamilton; Pei-Xiang Xing; Geoffrey A Pietersz; Vasso Apostolopoulos; Hilary Vaughan; Vaios Karanikas; Peter Kyriakou; Ian F C McKenzie; Paul L R Mitchell Journal: Clin Cancer Res Date: 2006-02-01 Impact factor: 12.531
Authors: Mahsa Mohebtash; Kwong-Yok Tsang; Ravi A Madan; Ngar-Yee Huen; Diane J Poole; Caroline Jochems; Jacquin Jones; Theresa Ferrara; Christopher R Heery; Philip M Arlen; Seth M Steinberg; Mary Pazdur; Myrna Rauckhorst; Elizabeth C Jones; William L Dahut; Jeffrey Schlom; James L Gulley Journal: Clin Cancer Res Date: 2011-11-08 Impact factor: 12.531
Authors: Marijo Bilusic; Christopher R Heery; Philip M Arlen; Myrna Rauckhorst; David Apelian; Kwong Y Tsang; Jo A Tucker; Caroline Jochems; Jeffrey Schlom; James L Gulley; Ravi A Madan Journal: Cancer Immunol Immunother Date: 2013-12-07 Impact factor: 6.968