EHA 2019 | Modulation of AMG 330-mediated T-cell proliferation and cytotoxicity
Marion Subklewe, MD, Ludwig Maximilian University Hospital Munich, Munich, Germany, discusses her work investigating AML secretome and T-Cell function: modulation of AMG 330-mediated T-cell proliferation and cytotoxicity at the 24th Congress of the European Hematology Association (EHA) 2019, held in Amsterdam, Netherlands.
Transcript (edited for clarity)
We are very interested in utilizing T cell recruiting antibody constructs for the treatment of AML. While we’re still recruiting patients into the running phase one trials, we are looking in our pre-clinical model at parameters that might influence T cell recruiting antibody constructs, and efficacy of these constructs...
We are very interested in utilizing T cell recruiting antibody constructs for the treatment of AML. While we’re still recruiting patients into the running phase one trials, we are looking in our pre-clinical model at parameters that might influence T cell recruiting antibody constructs, and efficacy of these constructs. We’ve looked at the serum of bone marrow and of the peripheral blood, and looked at the influence on AMG’s 330 and C33 BiTE mediated a set toxicity on primary AML cells. Interestingly, we could show that the serum of the peripheral blood of AML patients has no effect, as has bone marrow serum from healthy donor, as well as bone marrow serum from AML patients in remissions. There we see, in a pre-clinical system, high efficacy of AMG’s 330 mediate a set toxicity.
However, if we take serum of AML patients with a high infiltration of blast, we see an abrogation of AMG’s 330 mediated cytotoxicity. This is not the case in all patients, but about 50% of the patients. So far we analyze 30 patients, we can see the clear compromise in T cell proliferation, and AMG’s 330 mediated cytotoxicity. Currently, clearly, we are trying to identify factors that are actually mediating this effect. So far, we can only say that it’s not cell-cell dependent. So doing transwell experiments we could show that is a soluble factor that is mediating the T cell inhibition and the inhibition of T cell proliferation.
Currently, we are looking at the separate home by mass spec trying to identify the factor. So far, we can only say, it’s not the common suspects that have already been shown like adenosine or something, blocking of these didn’t have any effect, so we are interested if we might be able to identify a novel factor that is inhibiting T cell proliferation, and might be key to know if we want to use AMG’s 330 or other T cell recruiting antibody construct in the setting of relapse refractory AML. And so far, we can only conclude that it’s more likely that these antibody constructs going to work in an MRD situation where you have to low number of infiltrating blast and a higher likelihood that the T cell function is not compromised.
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