Major pharmaceutical companies including Eli Lilly, AbbVie, and AstraZeneca are investing heavily in the development of in vivo CAR T cell therapies, according to a July 27 article. This new approach could address manufacturing and cost barriers that have limited patient access to traditional ex vivo CAR T treatments.
Currently, most CAR T therapies require extracting a patient's cells for genetic modification outside the body before reinfusion. In contrast, in vivo techniques generate engineered immune cells directly inside the patient. Mitchell Kapoor, senior biotech equity research analyst at H.C. Wainwright, said this technology "can fundamentally change how healthcare practitioners administer cell therapy," potentially shortening time to infusion and reducing costs.
Kostas Biliouris of Oppenheimer explained that in vivo methods eliminate the need for initial cell extraction and preconditioning chemotherapy: "In a sense, the body becomes the manufacturing site." However, Kapoor warned that moving manufacturing into patients introduces new risks: "Moving manufacturing into the patient solves access and cost, but it takes the most complicated step—engineering the cells—out of a facility you can inspect and moves that process...into a patient who you can’t inspect." He added that safety must be pristine for investors to be impressed.
Eli Lilly has made significant acquisitions this year with its $2.4 billion purchase of Orna Therapeutics and up to $7 billion deal for Kelonia Therapeutics. Orna's platform uses circular RNA delivered by lipid nanoparticles to prompt patients' bodies to create their own CAR T cells. A Lilly spokesperson said ex vivo approaches are “complex” and only reach a fraction of eligible patients; an in vivo method could minimize wait times and infrastructure needs.
Legend Biotech is also advancing an in vivo candidate (LB2501) targeting B cell malignancies without large pharma backing. Early Phase 1 data showed favorable response rates with no serious adverse events or dose-limiting toxicities reported so far. Legend CEO Ying Huang said these findings “reinforce our belief that in vivo approaches have the potential to complement existing cell therapy modalities.”
AbbVie entered partnerships worth up to $1.4 billion with Umoja Biopharma for its VivoVec platform as well as acquiring Capstan Therapeutics for up to $2.1 billion; both programs focus on enabling patients’ bodies to produce cancer-fighting immune cells internally.
AstraZeneca acquired EsoBiotec’s ENaBL platform for up to $1 billion total investment; early results from an investigational asset eradicated cancer in three out of five multiple myeloma patients but included one death due to neurotoxicity complications associated with immunotherapies—a risk AstraZeneca acknowledged while committing further development based on feasibility demonstrated so far.
