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CAR-T Moves Toward In Vivo Manufacturing, as Circio and Tcelltech Bet on a Non-Viral Vector Combination

The two companies are linking circular RNA expression technology with a non-integrating DNA vector, with the goal not of immediately launching a new therapy, but first of answering whether engineered T cells can be produced in vivo in a more durable and more controllable way.

By SURL BioNews

The next challenge for cell therapy is no longer only finding better antigens or stronger immune cells, but whether complex, expensive engineering processes that rely on ex vivo manufacturing can gradually be moved toward simpler in vivo operations. The CAR-T cell therapy research collaboration announced by Norway’s Circio Holding ASA and Germany’s Tcelltech GmbH is an early attempt along that path.

According to company announcements and reporting by Contract Pharma, the collaboration was jointly announced from Oslo and Mannheim on June 24, 2026. The two sides will combine Circio’s circVec circular RNA expression technology with Tcelltech’s nanoSMAR double-stranded, non-integrating vector platform to develop next-generation engineered T cell therapies. The collaboration is currently positioned as a research program. It has not yet entered clinical trials, and no financial terms or specific timeline have been disclosed.

CAR-T therapy typically requires removing a patient’s T cells, introducing a chimeric antigen receptor that can recognize cancer cells ex vivo, and then reinfusing the cells into the body. This process has demonstrated efficacy in some hematologic malignancies, but manufacturing time, cost, individualized quality control, and the limitations of viral vectors make it difficult to deploy at large scale and speed like conventional drugs. Non-viral, non-integrating vectors have therefore become a direction the industry continues to explore, especially with the aim of reducing the risk of gene insertion and increasing the capacity for genetic information that can be carried.

Under the companies’ plan, the research will proceed in stages. The first step will compare the strength and durability of gene expression in primary human T cells. If the results are supportive, the next step will be to generate CAR-T cells targeting CD19 and test their ability to kill tumor cells. CD19 is one of the most mature targets in the CAR-T field for B cell malignancies, so it can serve as a benchmark testbed for new vector technologies, rather than implying that the two companies have already selected a specific clinical product.

Circio argues that circVec can use the stability characteristics of circular RNA to extend the expression time of CAR or TCR in cells; Tcelltech says nanoSMAR has greater cargo capacity than traditional viral methods, making it suitable for incorporating more complex engineering designs. If the two technologies are compatible, they could theoretically support more durable receptor expression and pave the way for directly engineering immune cells in vivo.

However, the key issue for this type of collaboration remains evidence. The announcements currently provide the research design and platform rationale, but have not yet presented comparative data in primary human T cells, animal study results, toxicity assessments, or manufacturing consistency data. For in vivo cell therapy, which cells the vector enters, how long expression lasts, whether it triggers an immune response, and how the effect can be stopped or regulated when needed are all questions that must be answered before entering humans.

The significance of this collaboration, therefore, is not that it declares the CAR-T manufacturing model has been rewritten, but that it reflects how the cell therapy industry is extending its innovation focus from “the cells themselves” to “delivery and expression systems.” Only if early experiments can show that expression durability and tumor-killing function have indeed improved will Circio and Tcelltech move to the next, more difficult stage: turning an elegant vector concept into a therapy that can be manufactured, verified, and regulated.

References

  1. Contract Pharma
  2. Circio