Researchers Report First In Vivo CAR-T Cell Generation in Multiple Myeloma Patients in Nature Medicine
Investigators in China report that a single intravenous infusion of ESO-T01, a nanobody-directed lentiviral vector, generated functional anti-BCMA CAR-T cells directly inside patients with relapsed or refractory multiple myeloma, bypassing the need for ex vivo cell manufacturing, according to a phase 1 study published in Nature Medicine. The in vivo CAR-T approach produced objective responses in four of five treated patients, including three stringent complete remissions, without lymphodepleting chemotherapy or leukapheresis.
The ESO-T01 clinical trial (NCT06791681), conducted at sites including Tongji Hospital and Union Hospital in Wuhan, enrolled five consecutively treated male patients with a median of three prior lines of therapy. A second phase 1 study (NCT06691685) is also recruiting at Union Hospital. Full author affiliations and the corporate sponsor were not disclosed in the available abstract, though the proprietary product designation suggests involvement of a biotechnology company responsible for the vector's development.
A Single Infusion Replaces Weeks of Manufacturing
The study tested ESO-T01 at a dose of 0.2 × 10⁹ transduction units delivered as a single intravenous infusion. The vector is an immune-shielded lentiviral particle engineered with surface nanobodies that redirect its tropism to circulating T cells. Upon binding, the vector delivers a humanized anti-BCMA chimeric antigen receptor transgene that integrates into the T cell genome, converting the patient's own T cells into CAR-T cells without removing them from the body.
This approach eliminates three steps that define conventional CAR-T cell generation: leukapheresis to collect patient T cells, weeks-long ex vivo manufacturing at centralized facilities, and lymphodepleting chemotherapy conditioning prior to reinfusion. In the current study, patients received ESO-T01 without any of these interventions.
CAR-positive T cells were detectable in peripheral blood as early as day 7 post-infusion, with peak expansion around days 10 to 14. Both CD4-positive and CD8-positive CAR-T cell populations were generated. The cells persisted throughout the follow-up period, which extended to approximately six months.
Responses Deepened Over Time in a Heavily Pretreated Population
Four of five patients achieved objective responses. Three reached stringent complete remission and one achieved very good partial response. Responses deepened over time, with patients progressing sequentially from partial response to deeper remission categories. All four evaluable responders achieved minimal residual disease negativity at a sensitivity threshold of 10⁻⁵ by day 60, and all maintained that status at last follow-up. Soluble BCMA levels declined to the normal range in responders, consistent with elimination of malignant plasma cells.
One patient died before the first efficacy assessment due to spinal cord compression from progressive extramedullary myeloma. The investigators attributed this event to underlying disease rather than to ESO-T01.
At a median follow-up of 6.0 months, all responses remained ongoing. No formal statistical comparisons were performed given the sample size of five patients.
Safety Profile Showed Manageable Toxicity
No dose-limiting toxicities occurred at the tested dose. Cytokine release syndrome developed in four of five patients, but all events were grade 1 or grade 2 and were managed with standard supportive care, including tocilizumab in some cases. No immune effector cell-associated neurotoxicity syndrome was observed in any patient, a finding that contrasts with the approximately 10 to 20 percent incidence reported with approved ex vivo anti-BCMA CAR-T products such as idecabtagene vicleucel and ciltacabtagene autolcel.