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In immunology, what does it mean by the term 'expansion' of T cells ex-vivo and activate it (generally with reference to cancer immunotherapy)?

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In immunotherapy, the T cells need to hit a therapeutic dose. The dose is normally determined pre-clinically or in a phase I or I/II trial. A good example is the YESCARTA label dose information:

YESCARTA comprises a suspension of 2 × 10^6 CAR-positive viable T cells per kg of body weight, with a maximum of 2 × 10^8 CAR-positive viable T cells in approximately 68 mL (3).

YESCARTA commercial label

Lets run through a hypothetical situation based loosely on information obtained in this publication.

So say you have a cancer patient that weighs 70kg on the day they obtain a leukapheresis for their starting material. The manufacturing facility is going to say okay, we need to produced 2E6 viable CAR+ cells/kg for a 70kg patient in 68mL per the label indication. So your final product needs to have 140 million viable CAR+ cells.

The patient leukapheresis can go wildly different on a patient-specific basis due to factors such as current treatment or disease. Your separation method can result in loss. Cells die in their initial culture period pre-transduction, and they can die post-transduction. So case study in point from the paper I linked:

Their patient 029-03 ended up with 0.494E+09 cells in their leukapheresis. Transduction efficiencies aren't published for a lot of these, but lentiviruses are typically employed and efficiencies can range from 1-90% depending on numerous factors. The manufacturer needs a target efficiency of ~28% to hit 140E+06 total cells if they manage to isolate every single CD3+ cell, but if they're 85% viable for example, they still wont hit the target dose. So you need to expand the cells aka make them divide so you hit the target therapeutic dose.

You typically culture your cells in IL-2, a potent T cell stimulator, but activation can improve transduction and stimulate cell division aka expansion. You can use something like CD3/CD28 beads, for example. These provide the so-called signals 1 and 2 that stimulate T cells in a similar way antigen challenge would.

Let me know if anything is unclear.

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