PANVAC™-VF:: poxviral-based vaccine therapy targeting CEA and MUC1 in carcinoma

被引:61
作者
Madan, Ravi A. [1 ]
Arlen, Philip M. [1 ]
Gulley, James L. [1 ]
机构
[1] NCI, Clin Immunotherapy Grp, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA
关键词
cancer vaccine; carcinoembryonic antigen; carcinoma; CEA; epithelial mucin 1; MUC1; TRICOM; ANTIGEN-PRESENTING CELLS; HUMAN CARCINOEMBRYONIC ANTIGEN; COLONY-STIMULATING FACTOR; CYCLOOXYGENASE-2 INHIBITOR CELECOXIB; FAMILIAL ADENOMATOUS POLYPOSIS; INDEPENDENT PROSTATE-CANCER; METASTATIC RENAL-CANCER; T-LYMPHOCYTE EPITOPE; RANDOMIZED PHASE-II; HUMAN-TUMOR-MARKER;
D O I
10.1517/14712598.7.4.543
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
PANVAC (TM) is a cancer vaccine therapy delivered through two viral vectors recombinant vaccinia and recombinant fowlpox - which are given sequentially. Both vectors contain transgenes for the tumor-associated antigens epithelial mucin 1 and carcinoembryonic antigen, which are altered or overexpressed in most carcinomas. The vectors also contain transgenes for three human T cell costimulatory molecules required to enhance immune response: B7.1, intracellular adhesion molecule-1 and leukocyte function-associated antigen-3. PANVAC is injected subcutaneously and processed by the body's antigen-presenting cells. Preclinical studies have demonstrated the efficacy of PANVAC in inducing both carcinoembryonic antigen- and mucin 1-specific cytotoxic T lymphocyte responses in vitro and in murine models. Other strategies that enhance the immune response include the use of granulocyte-macrophage colony-stimulating factor and a prime-boost administration sequence. Clinical trials have demonstrated PANVAC's safety and its ability to induce antigen-specific T cell responses. Early clinical trials are evaluating PANVAC alone and in combination with conventional chemotherapy and/or radiation. Studies to date hold promise for the use of PANVAC as a means to stimulate the immune system against malignancies and to provide clinical benefit.
引用
收藏
页码:543 / 554
页数:12
相关论文
共 90 条
[1]  
Aarts WM, 2002, CANCER RES, V62, P5770
[2]   MECHANISM OF SYNERGY OF LEVAMISOLE AND FLUOROURACIL - INDUCTION OF HUMAN-LEUKOCYTE ANTIGEN CLASS-I IN A COLORECTAL-CANCER CELL-LINE [J].
ABDALLA, EE ;
BLAIR, GE ;
JONES, RA ;
SUELING, HM ;
JOHNSTON, D .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1995, 87 (07) :489-496
[3]  
Aquino A, 1998, CLIN CANCER RES, V4, P2473
[4]   A randomized phase II study of docetaxel alone or in combination with PANVAC™-V (vaccinia) and PANVAC™-F (fowlpox) in patients with metastatic breast cancer (NCI 05-C-0229) [J].
Arlen, Philip M. ;
Pazdur, Mary ;
Skarupa, Lisa ;
Rauckhorst, Myrna ;
Gulley, James L. .
CLINICAL BREAST CANCER, 2006, 7 (02) :176-179
[5]   A randomized phase II study of concurrent docetaxel plus vaccine versus vaccine alone in metastatic androgen-independent prostate cancer [J].
Arlen, PM ;
Gulley, JL ;
Parker, C ;
Skarupa, L ;
Pazdur, M ;
Panicali, D ;
Beetham, P ;
Tsang, KY ;
Grosenbach, DW ;
Feldman, J ;
Steinberg, SM ;
Jones, E ;
Chen, C ;
Marte, J ;
Schlom, J ;
Dahut, W .
CLINICAL CANCER RESEARCH, 2006, 12 (04) :1260-1269
[6]   CARCINOEMBRYONIC ANTIGEN, A HUMAN-TUMOR MARKER, FUNCTIONS AS AN INTERCELLULAR-ADHESION MOLECULE [J].
BENCHIMOL, S ;
FUKS, A ;
JOTHY, S ;
BEAUCHEMIN, N ;
SHIROTA, K ;
STANNERS, CP .
CELL, 1989, 57 (02) :327-334
[7]   Treatment of human colon carcinoma cell lines with anti-neoplastic agents enhances their lytic sensitivity to antigen-specific CD8+ cytotoxic T lymphocytes [J].
Bergmann-Leitner, ES ;
Abrams, SI .
CANCER IMMUNOLOGY IMMUNOTHERAPY, 2001, 50 (09) :445-455
[8]   Cellular immunity in breast cancer patients completing taxane treatment [J].
Carson, WE ;
Shapiro, CL ;
Crespin, TR ;
Thornton, LM ;
Andersen, BL .
CLINICAL CANCER RESEARCH, 2004, 10 (10) :3401-3409
[9]   External beam radiation of tumors alters phenotype of tumor cells to render them susceptible to vaccine-mediated T-cell killing [J].
Chakraborty, M ;
Abrams, SI ;
Coleman, CN ;
Camphausen, K ;
Schlom, J ;
Hodge, JW .
CANCER RESEARCH, 2004, 64 (12) :4328-4337
[10]   Irradiation of tumor cells up-regulates Fas and enhances CTL lytic activity and CTL adoptive immunotherapy [J].
Chakraborty, M ;
Abrams, SI ;
Camphausen, K ;
Liu, KB ;
Scott, T ;
Coleman, CN ;
Hodge, JW .
JOURNAL OF IMMUNOLOGY, 2003, 170 (12) :6338-6347