Replies to post #453028 on NorthWest Biotherapeutics Inc (NWBO)

[Evaluate]

Great news, thanks Evaluate. That’s for the BATON system which cultures both dendritic cells and T-cells. Northwest Bio’s DCVax culturing process is a little different, but there’s aspects that this patent may cover in that process as well.
It will be interesting to see what becomes of this natural approach of using dendritic cells to introduce neoantigens to T-cells for a T-cell therapy, as opposed to engineering them.

October 2019:
Bioreactor for Autologous T-Cell Stimulation (BATON)
At Northeastern University, Shashi Murthy, PhD, and colleagues have developed the Bioreactor for Autologous T-Cell Stimulation (BATON) system. Featuring a highly modular design and incorporating fully disposable components (including disposable pumps and on-board reagent storage), BATON is designed to reduce manual operations in the co-culture of dendritic cells and T cells for neoantigen-based therapies. The system is being commercialized by a spinout called Flaskworks.

Co-culturing different cell types
In the next generation of T-cell cancer therapies, the T cells will have a library of molecules on their surfaces, and these molecules will recognize and target tumor-specific neoantigens. Bespoke T-cell therapies will be generated by selecting the patient’s own T cells against libraries of neoantigens. After the neoantigens are acquired by sequencing the tumor, they will be presented by the patient’s own dendritic cells (DCs). Because DCs are not abundant in circulating blood, they are typically prepared by first differentiating them from monocytes.

DCs and T cells may be co-cultured, but suitable instrumentation is required, says Shashi Murthy, PhD, professor of chemical engineering at Northeastern University. At the time this article was written he was scheduled to describe the design of such instrumentation at the Cell and Gene Therapy Bioprocessing and Commercialization conference.

“DCs so generated are adherent cells, and T cells are suspension cells,” Murthy explains. “So, you have to design a bioprocess to generate adherent cells and then be able to co-culture that adherent cell type with a suspension cell type.

“At the end of that process, you’re recovering the suspension cell type only. Further adding to the complication is the fact that this type of stimulation will sometimes need to be done in multiple cycles, [requiring] a fresh supply of DCs that are stimulated with a different batch of antigens.”

To keep T cells happy, instrumentation may incorporate a polystyrene-bottomed surface for optimized generation of DCs; a perfusion apparatus consisting of a tubing set; and a vessel with adequate headspace and perfusion-mediated gas exchange. “It’s sort of a hybrid between static vessels and gas-permeable bags,” Murthy says. “It’s all a closed system.”

According to Murthy, fully integrated automated systems are very capable but too expensive to adopt at the preclinical stage. “A lot of work is done manually and then translated into such systems,” he notes. “Now there’s a move in the industry to try to build closed systems that are sufficiently robust for clinical manufacturing and provide the benefits of automation, but at the same time are affordable enough to integrate into preclinical and Phase I environments.”

https://www.genengnews.com/insights/knocking-the-rough-edges-off-t-cell-therapy-manufacturing/