CAR-T Meeting 2025 | Facilitating CAR T-cell manufacturing: short-term CAR T-cells and in vivo CAR delivery
Christian Buchholz, PhD, Paul-Ehrlich-Institut, Langen, Germany, comments on the advancements in CAR T-cell manufacturing, mentioning two novel strategies being developed – short-term CAR T-cells and in vivo CAR delivery. Prof. Buccholz also highlights the safety of short-term CAR T-cells, which was investigated in murine models and in vitro assays. This interview took place at the EHA-EBMT 7th European CAR T-cell Meeting, held in Strasbourg, France.
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Transcript (AI-generated)
We have of course with the CAR T-cell products an enormous effort to make GMP, individualized GMP manufactured products for each patient individually. This has huge costs, takes a lot of time and there is therefore, a lot of research ongoing to facilitate this process. And one issue is short-term CAR T-cells, which simply means that the proliferation of the CAR T-cells after adding vector particles, which usually takes a week, up to two weeks maybe, where you expand T-cells and then inject them into the patient, and this is shortened down to just two days or so...
We have of course with the CAR T-cell products an enormous effort to make GMP, individualized GMP manufactured products for each patient individually. This has huge costs, takes a lot of time and there is therefore, a lot of research ongoing to facilitate this process. And one issue is short-term CAR T-cells, which simply means that the proliferation of the CAR T-cells after adding vector particles, which usually takes a week, up to two weeks maybe, where you expand T-cells and then inject them into the patient, and this is shortened down to just two days or so. So that means you add vector particles, and after 24/48 hours, these are the CAR T-cells that you inject into the patient. But this is still of course an individualized GMP process for each patient.
The in vivo CAR delivery means that you come to a product which is identical, an off-the-shelf product for all patients. That is the vector that is being injected into the patient and then will convert the T-cells to CAR T-cells in the patient. So that’s a huge difference. We have for both these strategies now clinical trials that recently started for the in vivo CAR T-cells. They started by the end of last year and will be exciting to see how this goes.
With the short-term CAR T-cells, we at the Paul Ehrlich Institute have recently had a closer look at their safety, and we had a surprising observation, that is, these short-term CAR T-cells had residual vector protein present on the CAR T-cells, and we could show that this residual vector protein, together with the expressed CAR, causes cytokine release, and in a mouse model, we’ve seen that mice really suffer within hours after injection of these short-term CAR T-cells from these cells. And we’ve also shown that in an in vitro assay where you simply have monocytes and short-term CAR T-cells co-cultivated, you can analyze the cytokine release and test your product whether it is of concern for cytokine release symptoms. That was published last year in EMBO Molecular Medicine and should hopefully help to better characterize these products. Thank you.
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