PAYLOAD COMPATIBILITY
Our system has been tested on a range of clinically relevant payloads, such as CAR, blood clotting factors, enzymes and cell receptors. All have produced lentivirus that can transduce target cells at a similar rate to the current system.
An additional benefit is that the production yield is more consistent in the Lentitek system.
Safety
Payload carryover into the downstream product has not only been demonstrated to have an impact for potency, but also in product safety. Aberrant psuodotyping of the vector was implicated as the cause of patient relapse after an ex vivo CAR-T treatment. (see publication here).
In this example the presence of B-cells in during ex vivo transduction was postulated as the root cause of treatment failure. However, it was also shown that if B-cells are present they can be transduced to present the CAR payload. This could cause potential issues with epitope escape if the transduced B-cells have CD19 masked by the CAR.
Even where the payload does not present a functional issue, carryover into the product may have other unwanted effects; such as an immune response.
Quality
The downstream purification process will find it tricky to deal with inclusion of the payload either into or on the surface of the lentivirus. However, even where payload is distinct from the vector, the presence of the payload can cause issues.
It is therefore best practice to begin processing with as high a quality vector as possible.
The Lentitek system will allow you to improve product quality with only a minor change to your setup.