CAR-T's Third Wave: Bio-O-Sigma Pioneers Innovative Technology to Enable Global Pharmaceutical Companies

Within a few months, the in vivo CAR-T therapy has repeatedly sparked industry events. AbbVie acquired Capstan Therapeutics for $21 billion in cash, gaining its first-in-class anti-CD19 in vivo CAR-T project CPTX2309 and proprietary targeted Lipid Nanoparticle (tLNP) platform; AstraZeneca also acquired EsoBiotec for $10 billion, laying out its nanobody-based virus platform and multiple in vivo CAR-T pipelines.

Global giants are vying for attention, with a clear logic: compared to traditional ex vivo CAR-T (ex vivo CAR-T), in vivo CAR-T is faster, cheaper, safer, and easier to scale up, potentially realizing universal cell therapy, hailed as the "third wave" of CAR-T. In vivo CAR-T can bypass complex cell collection and external operations, directly delivering the CAR gene into the T cells through a carrier molecule, achieving "in situ reprogramming," greatly reducing treatment barriers, costs, and operational complexity.

Nanobodies: The Key Engine for Precise Delivery and Structural Innovation

(1) Precise Delivery: Nanobodies Help Target T Cells In vivo CAR-T therapy's breakthrough lies in precise delivery. How to ensure the carrier molecule specifically enters T cells is the key bottleneck for efficacy and safety. Existing clinical trial data has confirmed nanobodies' delivery advantages. For example, Interius BioTherapeutics used a CD7 nanobody segment-modified viral vector to target T/NK cells, achieving complete tumor clearance in mouse models and obtaining FDA approval; Capstan Therapeutics utilized LNP to deliver CD8-targeted CAR mRNA for autoimmune disease treatment.

(2) Reconstructing CAR Structure: A Ideal Module Replacing scFv Traditional CAR structures often use scFv (single-chain antibody variable fragment) as the recognition module, but it has size-related issues, including instability, aggregation, and high immunogenicity. In contrast, nanobodies are naturally single-domain structured, stable, low-immunogenic, and suitable for CAR recognition module redesign. Their size advantage also makes them naturally compatible with dual-specific or multivalent CAR designs, enhancing therapeutic efficacy while preventing tumor immune escape.