A Randomized Phase 2.5 Study of (153)Sm-EDTMP (Quadramet) With or Without a PSA/TRICOM Vaccine in Men With Androgen-Insensitive Metastatic Prostate Cancer

Background:
No treatment is known to improve survival for prostate cancer patients who have not been helped by previous treatments with hormones and chemotherapy.
An experimental vaccine called prostate specific antigen (PSA)/TRICOM contains genes for a protein produced by prostate cancer cells called prostate-specific antigen (PSA). The vaccine can trigger the immune system to make cells that may be able to recognize and attack the cancer cells that make PSA.
Granulocyte macrophage colony stimulating factor (GM-CSF) is an approved drug that is usually given to increase a patient's white blood cell count or to stimulate the immune system.
1Samarium-153-ethylene diamine tetramethylene phosphonate (53Sm-EDTMP) is a radioactive drug that has been approved for many years to treat advanced prostate cancer. It is given through a vein and can be targeted directly to tumors in the bone where it can relieve pain caused by bone lesions. Radiation also increases the level of certain proteins inside the tumor, making it easier for the immune system to find and kill the tumor cells.
When laboratory mice were given just vaccine, just radiation, or a combination of both, the combination was most effective in treating tumors.
Objectives:
-To determine if combined treatment with PSA/TRICOM vaccine and 153Sm-EDTMP radiation can delay progression of prostate cancer better than radiation alone.
Eligibility:
-Patients who have advanced prostate cancer that has worsened despite treatments with hormones, have two or more bone lesions related to their prostate cancer, and have had prior treatment with docetaxel chemotherapy.
Design:
Patients are randomly assigned to receive radiation alone (Arm A) or radiation with vaccine and sargramostim (Arm B).
Arm A receives 153Sm-EDTMP radiation starting on study day 8 and repeated every 12 weeks.
Arm B receives a priming vaccine on study day 1 and radiation on day 8. Radiation therapy is repeated every 12 weeks. Boosting vaccines are given on days 15 and 29 and then monthly. GM-CSF is given with each vaccination (on the day of the vaccination and for the next 3 days) to enhance the immune response. Vaccinations and GM-CSF are given as injections under the skin, usually in the thigh. Radiation therapy is given through a vein.
Patients are monitored regularly with physical examinations, blood and urine tests, and scans to evaluate safety and treatment response.
Patients who are human leukocyte antigen serotype within HLA-A A serotype group (HLA-A2)-positive undergo apheresis, a procedure similar to donating blood, for obtaining immune cells called lymphocytes to measure the immune response to the vaccine.

开始日期2007-02-01

申办/合作机构

National Cancer Institute

NCT00087373 / Terminated临床2期IIT

Phase II Study of Intratumoral Injection of rF-TRICOMTM in Patients With Metastatic Melanoma Who Have Detectable Tumor Associated T Cells

Vaccines may make the body build an immune response to kill tumor cells. Injecting a vaccine directly into a tumor may cause a stronger immune response and kill more tumor cells. This phase II trial is studying how well vaccine therapy works in treating patients with metastatic melanoma.

开始日期2004-06-01

申办/合作机构

National Cancer Institute

NCT00072137 / Terminated临床1期IIT

Phase I Study of Intravesical Recombinant Fowlpox - GM-CSF (rF-GM-CSF) and/or Recombinant Fowlpox-TRICOM (rF-TRICOM) in Patients With Bladder Carcinoma Scheduled for Cystectomy

This phase I trial studies the side effects and best dose of vaccine therapy given directly into the bladder in treating patients who are undergoing surgery to remove all or part of the bladder. Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells. Giving a vaccine directly into the bladder before surgery may cause a stronger immune response and keep tumor cells from coming back after surgery.

开始日期2003-10-01

申办/合作机构

National Cancer Institute

100 项与 Recombinant fowlpox-TRICOM vaccine(NCI) 相关的临床结果

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100 项与 Recombinant fowlpox-TRICOM vaccine(NCI) 相关的转化医学

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100 项与 Recombinant fowlpox-TRICOM vaccine(NCI) 相关的专利（医药）

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项与 Recombinant fowlpox-TRICOM vaccine(NCI) 相关的文献（医药）

2014-05-01·Vaccine3区 · 医学

A pan inhibitor of DASH family enzymes induces immunogenic modulation and sensitizes murine and human carcinoma cells to antigen-specific cytotoxic T lymphocyte killing: implications for combination therapy with cancer vaccines

3区 · 医学

Article

作者: Hodge, James W ; Jones, Barry ; Wu, Wengen ; Zhao, Peng ; Donahue, Renee N ; Bachovchin, William W ; Lai, Jack H ; Tsang, Kwong-Yok ; Duncan, Brynn B ; Kiritsy, Christopher P ; Fry, Terry J ; Liu, Yuxin

Recent studies have suggested that pan inhibitors of dipeptidyl peptidase-4 activity and/or structure homologs (DASH), including ARI-4175, can mediate tumor regression by immune-mediated mechanisms. This study assessed the potential of combining ARI-4175 with cancer vaccines. We evaluated ARI-4175's effect on immunogenic modulation, ability to sensitize tumor cells to antigen-specific CTL killing, effect on immune-cell subsets and function, and antitumor activity in 2 tumor models, both as a monotherapy and in combination with a recombinant viral or dendritic cell (DC)-based tumor-cell vaccine. ARI-4175's effects on the growth, surface phenotype, and antigen-specific CTL-mediated lysis of murine and human carcinoma cell lines were assessed in vitro. In vivo, C57BL-6 mice were treated orally with ARI-4175, after which splenocytes were assessed by flow cytometry and functional assays. Antitumor studies were performed in murine models of colon carcinoma (MC38-CEA(+) in CEA-transgenic C57BL-6 mice) and rhabdomyosarcoma (M3-9-M in C57BL-6 mice). Mice received oral ARI-4175 alone or in combination with a vaccine consisting of recombinant vaccinia/fowlpox CEA-TRICOM (colon model) or a DC-based tumor-cell vaccine (rhabdomyosarcoma model). Exposure to ARI-4175 had no effect on the proliferation or viability of carcinoma cells in vitro; however, it did alter tumor phenotype, making murine and human tumor cells more sensitive to antigen-specific CTL killing. Assessment of immune-cell subsets and function indicated that ARI-4175 increased levels of natural killer cells and DCs. Detrimental immune effects, including reduced T effector cells and increased immunosuppressive cells (Tregs, MDSCs), were normalized when treatment stopped, suggesting that scheduling is critical when combining this agent with vaccine. As a monotherapy, ARI-4175 had potent antitumor activity in both tumor models, and had even greater effects when combined with a vaccine (either DC-based or poxviral vector based). These findings provide the rationale for the combined use of cancer immunotherapy with DASH enzyme inhibitors such as ARI-4175.

2010-10-01·International Journal of Cancer1区 · 医学

Effect of a small molecule BCL‐2 inhibitor on immune function and use with a recombinant vaccine

1区 · 医学

Article

作者: Helen Sabzevari ; Shinji Takai ; Maria Giovanna Di Bari ; Benedetto Farsaci ; Jeffrey Schlom ; James W. Hodge ; Jack P. Higgins

AbstractSmall molecule BCL‐2 inhibitors are being examined as monotherapy in phase I/II clinical trials for several types of tumors. However, few data are available about the effect of BCL‐2 inhibitors on immune function. The aims of our study were to investigate the effect of a small molecule BCL‐2 inhibitor on immune function and determine the most effective way of combining this inhibitor with a recombinant vaccine to treat tumors. The in vitro effect of the pan‐BCL‐2 inhibitor GX15‐070 was assessed in mouse CD8 T lymphocytes at 2 different stages of activation as well as regulatory T lymphocytes (Treg). The in vivo effect of GX15‐070 after recombinant vaccinia/fowlpox CEA‐TRICOM vaccination was analyzed in tumor‐infiltrating lymphocytes, and in splenocytes of mice bearing subcutaneous tumors. The therapeutic efficacy of such sequential therapy was measured as a reduction of pulmonary tumor nodules. Activated mature CD8 T lymphocytes were more resistant to GX15‐070 as compared to early‐activated cells. Treg function was significantly decreased after treatment with the BCL‐2 inhibitor. In vivo, GX15‐070 was given after vaccination so as to not negatively impact the induction of vaccine‐mediated immunity, resulting in increased intratumoral activated CD8:Treg ratio and significant reduction of pulmonary tumor nodules. Our study is the first to show the effect of a small molecule BCL‐2 inhibitor on the immune system and following a vaccine. It is also the first to demonstrate the efficacy of this sequence in reducing tumors in mouse models, providing a rationale for the design of combinational clinical studies.

2005-03-15·Clinical Cancer Research1区 · 医学

Induction of an Antigen Cascade by Diversified Subcutaneous/Intratumoral Vaccination Is Associated with Antitumor Responses

1区 · 医学

Article

作者: Hodge, James W. ; Kudo-Saito, Chie ; Schlom, Jeffrey

AbstractPurpose: Cancer vaccines targeting tumor-associated antigens are being investigated for the therapy of tumors. Numerous strategies, including the direct intratumoral (i.t.) vaccination route, have been examined. For tumors expressing carcinoembryonic antigen (CEA) as a model tumor-associated antigen, we previously designed poxviral vectors that contain the transgenes for CEA and a triad of T-cell costimulatory molecules, B7-1, intercellular adhesion molecule-1, (ICAM-1), and leukocyte function associated antigen-3 (LFA-3) (CEA/TRICOM). Two types of poxvirus vectors were developed: replication-competent recombinant vaccinia and replication-defective recombinant fowlpox. We have shown previously that a vaccine regimen composed of priming mice s.c. with recombinant vaccinia-CEA/TRICOM and boosting i.t. with recombinant fowlpox-CEA/TRICOM was superior to priming and boosting vaccinations using the conventional s.c. route in inducing T-cell responses specific for CEA. These studies also showed that CEA was needed to be present both in the vaccine and in the tumor for therapeutic effects.Experimental Design: To determine specific immune responses associated with vaccination-mediated tumor regression, CEA-transgenic mice bearing CEA+ tumors were vaccinated with the CEA/TRICOM s.c./i.t. regimen, and T-cell immune responses were assessed.Results: In CEA+ tumor-bearing mice vaccinated with the CEA/TRICOM s.c./i.t. regimen, T-cell responses could be detected not only to CEA encoded in vaccine vectors but also to other antigens expressed on the tumor itself: wild-type p53 and an endogenous retroviral epitope of gp70. Moreover, the magnitude of CD8+ T-cell immune responses to gp70 was far greater than that induced to CEA or p53. Finally, the predominant T-cell population infiltrating the regressing CEA+ tumor after therapy was specific for gp70.Conclusion: These studies show that the breadth and magnitude of antitumor immune cascades to multiple antigens could be critical in the therapy of established tumors.

100 项与 Recombinant fowlpox-TRICOM vaccine(NCI) 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
黑色素瘤	临床2期	美国	National Cancer Institute	2004-06-30

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00450619 (CTgov)	临床2期	去势抵抗性前列腺癌	44	Sargramostim+Recombinant fowlpox-TRICOM vaccine+Recombinant vaccinia-TRICOM vaccine	繭餘製製選觸範製築鏇(觸餘鹽積齋獵網憲鹽齋) = 餘繭壓遞鹹醖顧繭構鬱醖觸夢鹹選艱鏇遞獵構 (網獵糧淵築衊觸齋鑰鹹, 範鹹構襯構膚壓壓鏇遞 ~ 願築遞鬱製衊願窪築襯) 更多	-	2013-07-01
ASCO2004	临床1期	前列腺癌	15	recombinant Fowlpox-PSA (L155)-TRICOM (rF) (rF alone)	築製網艱蓋膚鹽獵鑰願(選顧觸範襯鹽窪淵積觸) = 齋製繭製窪衊壓襯願積獵鑰廠壓鑰夢鏇廠餘淵 (窪獵構繭鏇範選鏇窪積 ) 更多	-	2004-07-15
ASCO2004	临床1期	前列腺癌	15	recombinant Fowlpox-PSA (L155)-TRICOM (rF) (rV followed by rF)	築製網艱蓋膚鹽獵鑰願(選顧觸範襯鹽窪淵積觸) = 糧夢襯顧衊蓋憲願鹹構獵鑰廠壓鑰夢鏇廠餘淵 (窪獵構繭鏇範選鏇窪積 ) 更多	-	2004-07-15