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Celldex Therapeutics, Inc. Message Board

  • mswrichmond mswrichmond Oct 21, 2013 10:57 PM Flag

    Good reports coming in November 8 and 9 meeting poster session.

    The title says it all: Agonistt Anti-Human CD27 Monoclonal Antibody Induces T Cell Activation and Tumor Immunity in Human CD27–Transgenic Mice. Title of an article from jimmunol dot org.

    The Journal of Immunology, October 15, 2013 vol. 191, no. 8 , pages 4174-4183. If you can find it, pay the $10 fee and read the article, it's fantastic. Somebody is shorting this stock so they can buy it at a cheaper price.

    Sentiment: Strong Buy

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    • Missed seeing this story earlier. Thanks for posting.

      Sentiment: Strong Buy

    • Very interesting find- you will note that this article was published online on September 11, 2013 when CLDX traded at close to the same price where it is now! How strange the market is?

    • Read the article, whippersnapper is right.. Nice to have these guys (msw and whipper) looking out for us.

      Sentiment: Strong Buy

    • Bump to the top. I highly recommend reading this article that mswrichmond found. The $10 fee for accessing the article is nominal, considering the amount of money any sincere long would have invested in this company. The graphs showing the survival of tumer-challenged mice that have received CDX-1127 are especially worth viewing. It will give you confidence to hold onto your shares during this time that is testing the nerves of some.

      Sentiment: Strong Buy

    • Thanks for your DD.

      Sentiment: Strong Buy

    • I purchased the article and read it. The technical discussion of the methods is above my head, but the conclusions stated that the treatment 1F5, which is CDX-1127 in human trials, enabled tumor-challenged mice to live much longer: "1F5 was effective at dose levels as low as 10 mg (50 mg total dose) in extending the survival of mice challenged systemically with BCL1 lymphoma cells; however, most mice eventually succumbed to the tumor. We only tested the highest dose of 600 mg in the s.c. colon tumor model CT26 and found that the majority of animals survived the tumor challenge if treated early (starting day 3 after tumor challenge), which was characterized by slow tumor growth and eventual complete regression."

      Furthermore, "Importantly, the mice that underwent tumor regression from the initial challenge were resistant to a subsequent administration of CT26 tumor cells given 3 mo after initial treatment with 1F5, indicating that a memory response likely had been established."

      Finally, "Collectively, these data demonstrate that targeting hCD27 with 1F5 in hCD27-Tg mice can induce T cell activation leading to enhanced Ag-specific immunity and durable antitumor efficacy."

      The article ends, "These data support 1F5 as a promising candidate for clinical investigation. Phase 1 studies with 1F5, under the name CDX-1127, in patients with advanced solid tumors or hematological malignancies are ongoing."

      Note "slow tumor growth and eventual complete regression", "resistant to subsequent administration of... tumor cells", and "immunity and durable antitumor efficacy" from the article's conclusion. We shall see on November 7 just how promising a treatment CDX-1127 is turning out to be. Signs point to a BLOCKBUSTER REVOLUTIONARY CANCER TREATMENT.

      Sentiment: Strong Buy

    • Here is the article abstract, for what it's worth. Note the reference to "potent antitumor activity" and "protective immunity". Words are significant. Expect the CDX-1127 data released on November 7 to be spectacular. CDX-1127 looks to be a cancer killer.

      ABSTRACT: The CD70/CD27 pathway plays a significant role in the control of immunity and tolerance, and previous studies demonstrated that targeting murine CD27 (mCD27) with agonist mAbs can mediate antitumor efficacy. We sought to exploit the potential of this pathway for immunotherapy by developing 1F5, a fully human IgG1 mAb to human CD27 (hCD27) with agonist activity. We developed transgenic mice expressing hCD27 under control of its native promoter for in vivo testing of the Ab. The expression and regulation of hCD27 in hCD27-transgenic (hCD27-Tg) mice were consistent with the understood biology of CD27 in humans. In vitro, 1F5 effectively induced proliferation and cytokine production from hCD27-Tg–derived T cells when combined with TCR stimulation. Administration of 1F5 to hCD27-Tg mice enhanced Ag-specific CD8+ T cell responses to protein vaccination comparably to an agonist anti-mCD27 mAb. In syngeneic mouse tumor models, 1F5 showed potent antitumor efficacy and induction of protective immunity, which was dependent on CD4+ and CD8+ T cells. The requirement of FcR engagement for the agonistic and antitumor activities of 1F5 was demonstrated using an aglycosylated version of the 1F5 mAb. These data with regard to the targeting of hCD27 are consistent with previous reports on targeting mCD27 and provide a rationale for the clinical development of the 1F5 mAb, for which studies in advanced cancer patients have been initiated under the name CDX-1127.

      Sentiment: Strong Buy

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