FG28113 Sep 2020 12:29
Reposted from Burble, interesting.....any more info on FG2811 would be appreciated
From what I can gather mAb2811 does seem an interesting find. The target that this antibody binds to (stage-specific embryonic antigen-4 ) is expressed on the surface of stem memory T-cells. The discovery of this is v.interesting indeed. The hyperspecific nature means as a tool it could be very useful in selecting stem cells from other background (terminally differentiated) cells with an incredible level of precision.
If we look at the current CAR-T therapies in use - we have Axicabtagene ciloleucel (yescarta) for Large B-cell lymphoma and we have Tisagenlecleucel (Kymriah) for B-cell acute lyphoblastic leukaemia. Each costs many hundreds of thousands of pounds per treatment. Each require a patient to have T-cells which are harvested, transformed, grown in the lab (which does often result in failure as cells do not expand enough), then delivered back into the patient. That's huge amounts of work, money, time and sadly the efficiency is not fantastic (a relatively high percentage of final product does not reach the grade necessary to be called the therapeutic drug). Furthermore, it's a balancing act - you've got to keep the patient alive long enough to be able to harvest their T-cells, yet you can't treat with high dose chemo or radiotherapy to kill off their leukaemia/lymphoma because it will kill the bone marrow and you need that to be able to produce their T-cells.
Now imagine using mAb2811 as a bait to harvest the stem memory T-cells. These TSCMs have the ability to self-renew and differentiate into other forms of T-cells. This gives you the opportunity to select TSCMs specifically and grow them in vitro. Take this further, you harvest TSCMs, genetically engineer them (CAR-T), they grow, you deliver back into the patient. It could save vast amounts of money for people within the CAR-T field (many players currently. Novartis, Kite Pharma, Gilead Sciences, ImmunoCore etc) by removing the bottle neck of selecting the right T-cells (you're starting with the juvenile one you could say) and being able to expand the one you've genetically engineered.
Also all CAR-Ts currently are against B-cell malignancies. Developing CAR-T therapies against T-cells is far more challenging due to the difference between therapeutic, normal and malignant T-cells. This mAb, could enable you to not only generate a CAR-T against malignant T-cells, but also add back a healthy TSCM afterwards which can expand and differentiate into different forms of T-cell down the line.
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