Blinatumomab and CLL

Blinatumomab and CLL

Some UK research and news of developments by the Cardiff CLL research team :

Blinatumomab is a bi-specific T-cell engager (BiTE).

Blinatumomab currently in trials treating B-NHL has shown clinical responses in patients with both indolent and aggressive diseases is now being looked at closely for CLL and is showing early in vitro results that it is effective at aiding our own depleted immune system against CLL Cells..

Researchers were concerned that the known immunodeficiencies displayed in CLL would reduce this effect with CLL tumour cells. However "Blinatumomab retains efficacy even in the presence of CLL activation and prosurvival signals"..


by Ryan Wong, Chris Pepper, Paul Brennan, Dirk Nagorsen, Stephen Man, and Chris Fegan

published ahead of print June 28, 2013,


“Chronic lymphocytic leukemia is an incurable B-cell malignancy that is associated with tumor cell-mediated T-cell dysfunction. It therefore represents a challenging disease for T-cell immunotherapeutics.

The CD19/CD3 bi-specific antibody construct blinatumomab (AMG103 or MT103) has been tested clinically in non-Hodgkin's lymphoma and acute lymphoblastic leukemia but has not been assessed in chronic lymphocytic leukemia. We tested whether blinatumomab could overcome T cell dysfunction in chronic lymphocytic leukemia in vitro.

Blinatumomab was tested on PBMC from 28 patients (treatment naive and previously treated). T cell activation and function, as well as cytotoxicity against leukemic tumor cells were measured.

Blinatumomab induced T-cell activation, proliferation, cytokine secretion and granzyme B release in a manner similar to stimulation with anti-CD3/anti-CD28 beads. However, only blinatumomab was able to induce tumor cell death and this was found to require blinatumomab-mediated conjugate formation between T-cells and tumor cells.

Cytotoxicity of tumor cells was observed at very low T cell:tumor cell ratios. A 3-D model based on confocal microscopy, suggested that up to 11 tumor cells could cluster round each T cell.

Importantly, blinatumomab induced cytotoxicity against tumor cells in samples from both treatment naïve and treated patients, and in the presence of co-culture pro-survival signals. The potent cytotoxic action of blinatumomab on tumor cells appears to involve conjugation of T cells with tumor cells at both the activation and effector stages. The efficacy of Blinatumomab in vitro, suggests that the bi-specific antibody approach may be a powerful immunotherapeutic strategy in chronic lymphocytic leukemia.”

READ THE Full paper PDF here:


What is Blinitumomab - from wikipedia

“Blinatumomab (MT103) is a drug that has anti-cancer properties. It belongs to a new class of constructed monoclonal antibodies, bi-specific T-cell engagers (BiTEs), that exert action selectively and direct the human immune system to act against tumor cells. Blinatumomab specifically targets theCD19 antigen present on B cells.”

Blinatumomab enables a patient's T cells to recognize malign B cells. A molecule of blinatumomab combines two binding sites: a CD3 site for T cells and a CD19 site for the target B cells. CD3 is part of theT cell receptor. The drug works by linking these two cell types and activating the T cell to exert cytotoxicactivity on the target cell


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7 Replies

  • Nice post Nick... thanks!

  • One in for the home side :-)

  • Absolutely!! This monoclonal has been around since 2002, and should people wish to learn more the original technology was taken over by try AMG-103 rather than MT-103 in a search.

    Chaya had an article on this BiTE technology, a few years ago..


  • Thanks Chris very helpful. Chaya's articles help with history and explain how the molecule works. A very exciting approach,. It takes time but technology eventually filters down to us,


  • Terry Hamblin wrote a couple of blogs on this technology in June 2011. His daughter actually did her PhD on it!




  • Thank you Neil, Interesting That the Hamblins believed then and the Prof commented: "Certainly a winner, but it needs more work. I would expect a CLL trial shortly, but as you will see from my subsequent posts on this the situation in adult ALL is more urgent."

    Maybe Cardiff's work is paving the way? (will have to ask their opinion on my next visit to UHW)

    I am interested in the German trial mentioned by Chaya that was recruiting SLL patients in a 2011 clinical trial study and when data from this will be available? (anyone know where to look?) Intriguing that risk of "side effects seems to be caused by the release of cytokines in those with circulating tumor cells", Prof Hamblin's comment further peaked my interest as my own developments have redirected my attention to studies focusing on the SLL disease presentation .

    Yes Chris I now can see that the Germans were reporting on CLL studies with this technology as far back as 2003 it seems the focus moved onto ALL. this was Received 5 March 2002; Accepted 19 December Leukaemia Journal a German study: "Efficient elimination of chronic lymphocytic leukaemia B cells by autologous T cells with a bispecific anti-CD19/anti-CD3 single-chain antibody construct"

    All very interesting


  • Hi The more drugs and treatments that come on line the better as one size often does not fit all.

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