04 January 2022

Promising results have been seen in two clinical trials of chimeric antigen receptor T (CAR-T) cells targeting the CD19 antigen, for patients with leukaemia and lymphoma. The trials demonstrated that manufacturing CAR-T cells locally, rather than in a central commercial lab, could potentially lead to quicker and more effective control of tumours.

The protein CD19 is expressed by most B-cell malignancies, and immunotherapies which target it are effective in treating adults and children with these malignancies.

Dr Jane Reese-Koc of Case Western Reserve University, Cleveland, USA, and her team developed a new CD19-targeting chimeric antigen receptor (CAR), which they called CAR19.

When produced by T cells, their CAR “shows potent target-specific cytotoxicity response in vitro and is effective in rejecting CD19 positive tumours in an in vivo lymphoma model,” they reported in Nature Communications. Fresh CAR-T cells controlled tumours in mice quicker compared to CAR-T cells which had previously been frozen, or ‘cryopreserved’.

They then went on to test their new CAR-T cells treatment in two phase I trials, manufacturing the CAR-T product locally at the trial sites in Cleveland, USA, and Moscow, Russia.

“Place-of-care manufacturing is defined as near the point of patient treatment, allowing cell products to be produced and infused without the need for cryopreservation,” they write.

The trials involved 31 children with relapsed or refractory B-cell acute lymphocytic leukaemia (ALL), and 23 adults with B-cell non-Hodgkin’s lymphoma (NHL).

Of the patients treated with CAR‑T cells, 89% of the paediatric ALL and 73% of adult NHL patients saw a complete response.

Among the ALL patients with a complete response, the one-year survival rate was 79% and median duration of response was 10.2 months. For NHL patients with a complete response, one-year survival rate was 92.9%.

“Place-of-care manufacturing may improve performance and accessibility by obviating the need to cryopreserve and transport cells to centralised facilities,” said Dr Reese-Koc. “The results of this study support the safety and efficacy of this approach.”

Co-author Dr David Wald added: “One of the major advantages of this approach is the ability to treat patients significantly quicker than is feasible with commercial chimeric antigen receptor T products.

“Commercial products can take three to six weeks to be manufactured. The time savings to treatment with the method is important for these patients that have advanced malignancies. We are working with partners to develop even more rapid methods to shorten the manufacturing method down to a single day.”

Source:

Maschan M, Caimi PF, Reese-Koc J, Sanchez GP, Sharma AA, Molostova O, Shelikhova L, Pershin D, Stepanov A, Muzalevskii Y, Suzart VG, Otegbeye F, Wald D, Xiong Y, Wu D, Knight A, Oparaocha I, Ferencz B, Roy A, Worden A, Kruger W, Kadan M, Schneider D, Orentas R, Sekaly RP, de Lima M, Dropulić B. (2021) “Multiple site place-of-care manufactured anti-CD19 CAR-T cells induce high remission rates in B-cell malignancy patients.” Nature Communications, doi: 10.1038/s41467-021-27312-6

Link: https://www.nature.com/articles/s41467-021-27312-6

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