Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official. Federal government websites often end in . gov or . mil. Before sharing sensitive information, make sure you’re on a federal government site VSports app下载. .

Https

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely V体育官网. .

. 2015 Mar 28:13:102.
doi: 10.1186/s12967-015-0460-x.

"V体育官网" A phase I clinical trial of adoptive T cell therapy using IL-12 secreting MUC-16(ecto) directed chimeric antigen receptors for recurrent ovarian cancer

Affiliations

VSports注册入口 - A phase I clinical trial of adoptive T cell therapy using IL-12 secreting MUC-16(ecto) directed chimeric antigen receptors for recurrent ovarian cancer

Mythili Koneru et al. J Transl Med. .

Abstract (V体育ios版)

Purpose: Recurrent platinum-resistant ovarian cancer has no curative options, necessitating the development of novel treatments, including immunotherapy VSports手机版. .

Rationale: Patient-derived T cells can be genetically modified to express chimeric antigen receptors (CARs) specific to tumor-associated antigens in an HLA-independent manner, with promising preclinical results. MUC16(ecto) is highly expressed on most epithelial ovarian carcinomas but at low levels on normal tissues, offering an excellent immunotherapeutic target for this cancer. CAR T cells further modified to secrete IL-12 show enhanced cytotoxicity, persistence, and modulation of the tumor microenvironment. V体育安卓版.

Design: We propose a dose escalation phase I clinical trial for patients with recurrent MUC-16(ecto+) ovarian cancer to test the safety of intravenous and intraperitoneal administration and the preliminary efficacy of autologous IL-12 secreting, MUC-16(ecto) CAR T cells containing a safety elimination gene. V体育ios版.

Innovation: This trial targets MUC-16(ecto), a novel and promising tumor-associated antigen. This will be the first time CAR T cells are injected intraperitoneally directly into the site of the tumor within the abdomen in humans VSports最新版本. Furthermore, the ability of genetically modified cells to secrete IL-12 will potentially enhance CAR T cell persistence and modulate the tumor microenvironment. For safety purposes, an elimination gene has been incorporated into the CAR T cells to mitigate any on-target, off-tumor or other unforeseen toxicity. .

PubMed Disclaimer

Figures

Figure 1
Figure 1
Schematic diagram of MUC-16 structure.
Figure 2
Figure 2
Secretion of IL-12 by CAR-modified T cells may improve cytotoxicity of CAR + T cells and reverse anergy in tumor infiltrating lymphocytes.
Figure 3
Figure 3
Treatment schema.
Figure 4
Figure 4
Severe cytokine release syndrome management algorithm.

"VSports在线直播" References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5–29. doi: 10.3322/caac.21254. - DOI - PubMed
    1. Bookman MA. Standard treatment in advanced ovarian cancer in 2005: the state of the art. Int J Gynecol Cancer. 2005;15(Suppl 3):212–20. doi: 10.1111/j.1525-1438.2005.00444.x. - DOI - PubMed
    1. du Bois A, Luck HJ, Meier W, Adams HP, Mobus V, Costa S, et al. A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst. 2003;95:1320–9. doi: 10.1093/jnci/djg036. - VSports - DOI - PubMed
    1. Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 2003;21:3194–200. doi: 10.1200/JCO.2003.02.153. - DOI - PubMed
    1. Chu CS, Kim SH, June CH, Coukos G. Immunotherapy opportunities in ovarian cancer. Expert Rev Anticancer Ther. 2008;8:243–57. doi: 10.1586/14737140.8.2.243. - DOI - PubMed

MeSH terms

"V体育平台登录" Grants and funding