Tocilizumab

Investigators in China report that a single intravenous infusion of ESO-T01, a nanobody-directed lentiviral vector linked to AstraZeneca, 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 I 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 I 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. 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 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 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. No severe or unexpected infections were reported. The absence of lymphodepleting chemotherapy in the treatment protocol preserved baseline immune function, which may have contributed to the infection profile. The investigators reported no evidence of insertional oncogenesis or off-target transduction of non-T cell lineages. The in vivo CAR-T landscape ESO-T01 was discovered by Belgium-based EsoBiotec and acquired by AstraZeneca in a March 2025 deal worth up to USD 1 billion. Multiple companies are pursuing in vivo CAR-T therapy through different delivery platforms. Umoja Biopharma has initiated a Phase I trial of UB-VV100, a lentiviral-based in vivo CAR-T targeting CD19 for B-cell malignancies. Capstan Therapeutics, acquired by Roche in 2024, is developing lipid nanoparticle-based mRNA delivery to T cells, an approach that produces transient rather than stable CAR expression. Kelonia Therapeutics, Orna Therapeutics, and Interius BioTherapeutics are pursuing related platforms at the preclinical stage. The approved multiple myeloma treatment landscape already includes two ex vivo anti-BCMA CAR-T products — idecabtagene vicleucel from BMS/2seventy bio and ciltacabtagene autolcel from Janssen/Legend Biotech — along with BCMA-targeting bispecific antibodies teclistamab and elranatamab. Bispecific antibodies are off-the-shelf and address the same accessibility problem that in vivo approaches aim to solve, but they require continuous dosing and have not demonstrated the depth of remission associated with CAR-T therapy. Several allogeneic CAR-T programs targeting BCMA, including Caribou Biosciences’ CB-011 and programs from Allogene Therapeutics and Poseida Therapeutics, are also in early clinical development. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website