In Vivo CAR-T Therapy ESO-T01 Shows Early Activity in Multiple Myeloma Study

Mar,27 2026-

AstraZeneca’s push into in vivo cell therapy continues to draw attention following the publication of early clinical data for ESO-T01, an investigational BCMA-targeted in vivo CAR-T therapy, in the journal Nature Medicine. The Phase 1 study, conducted in China, evaluated the therapy in patients with relapsed or refractory multiple myeloma and provided early insights into both its potential efficacy and safety profile.

ESO-T01 was developed using EsoBiotec’s lentiviral vector platform, which AstraZeneca acquired in 2025 through a deal valued at $425 million upfront with up to $575 million in milestone payments. The technology is designed to generate CAR-T cells directly inside the patient’s body, eliminating the need for complex ex vivo cell manufacturing and potentially enabling “off-the-shelf” cell therapy.

In the Phase 1 study, four of five treated patients achieved objective responses, including three stringent complete remissions by day 60, suggesting preliminary antitumor activity. According to the study authors, the results provide early evidence supporting the feasibility of in vivo CAR-T cell generation using an immune-shielded viral vector system.

However, safety findings were mixed. While the therapy was described as generally well tolerated with no dose-limiting toxicities, all patients experienced grade 3 or higher adverse events. Cytokine release syndrome (CRS) occurred in four patients, reaching grade 3 severity in three cases, while common toxicities included transient cytopenias and reversible liver enzyme elevations. Three patients also experienced grade 2 infections.

One patient developed grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS) and died 19 days after treatment due to spinal cord compression associated with an extramedullary lesion. Extramedullary disease in multiple myeloma is known to be associated with more aggressive disease and poorer outcomes, and the authors noted that the event highlights the importance of careful anatomical risk assessment prior to administering in vivo CAR-T therapies.

CRS and ICANS are well-known side effects of traditional ex vivo CAR-T therapies, in which T cells are collected from a patient, genetically engineered outside the body, and reinfused. The study authors noted that although the types of toxicities seen with ESO-T01 were similar to conventional CAR-T treatments, the timing and sequence of events may reflect different biological mechanisms associated with in vivo CAR-T generation.

The results also raise questions about how ESO-T01 will compare with existing therapies in the highly competitive multiple myeloma CAR-T landscape. Currently approved treatments such as BCMA-targeting CAR-T therapies have demonstrated strong clinical efficacy, and newer candidates are continuing to show improving response rates over time.

Despite the early safety concerns, AstraZeneca maintains confidence in the in vivo cell therapy approach, emphasizing that all patients in the study had advanced, heavily pretreated multiple myeloma. According to the company, the study demonstrates that in vivo CAR-T therapy can generate clinical responses without the need for lymphodepletion or individualized cell manufacturing, potentially offering a more scalable treatment model.

Interest in in vivo genetic and cellular therapies continues to grow across the industry. Since AstraZeneca entered the field through the acquisition of EsoBiotec, other major pharmaceutical companies have also made strategic moves to develop next-generation in vivo platforms aimed at simplifying cell therapy manufacturing and expanding access to these treatments.

While the ESO-T01 data represent only an early clinical snapshot, the findings highlight both the promise and challenges of in vivo CAR-T technologies, an emerging therapeutic strategy that could reshape how cell therapies are delivered in the future.