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14 april 2026: Bron: Naturer 25 maart 2026

Vijf zwaar voorbehandelde patiënten met een recidief of ziekteprogressie van uitgezaaide Multiple Myeloma (botkanker - ziekte van Kahler) boekten uitstekende resultaten door een ​​eenmalige intraveneuze infusie van ESO-T01 – een zogeheten nanobody-gerichte, immuun afgeschermde lentivirale vector die zich richt op de receptor BCMA CAR. Bijzonder aan deze studie is dat er voor de productie van ESO-T01 vooraf geen leukafarese of chemotherapie nodig was. ESO-T01 richtte zich selectief op in bloed circulerende T-cellen en herprogrammeerde deze in het lichaam om het CAR-T medicijn tot expressie te brengen, waarna deze cellen zich vermenigvuldigden en een sterke antitumoractiviteit vertoonden zonder gezonde cellen aan te vallen. Blijkt uit een eerste verkennende studie bij 5 patiënten.

Ondanks de kleine studiegroep van slechts 5 patiënten was de effectiviteit wel opvallend positief: 4 van de 5 patiënten bereikten objectieve remissies, waaronder drie volledige aangetoonde complete remissies, met een restziekte (MRD) -negativiteit bij een gevoeligheid van 10⁻⁵ bij alle vier de evalueerbare patiënten op dag 60.

Het Cytokine-release-syndroom als ernstige bijwerking trad op bij 80% van de patiënten (3 patiënten hadden graad 3, 1 patiënt graad 2), die wel allemaal onder controle te krijgen waren met een standaardbehandeling. De meest voorkomende bijwerkingen waren voorbijgaande cytopenie en een behandelbare verhoging van de leverenzymen. Tijdens de studie overleed één patiënt als gevolg van ruggenmergcompressie veroorzaakt door extramedullaire laesies, wat nauw verband hield met de ziekteprogressie.

Hier een grafiek uit het studierapport gekopieerd

Nature Medicine: AstraZeneca's latest clinical data on in vivo CAR-T therapy shows effectiveness, but one death has been reported.

Hoewel de duurzaamheid onzeker blijft – de mediane follow-up was beperkt tot 6 maanden en de studie werd voortijdig beëindigd in 2025 – is het biologische bewijs van het concept overtuigend en heeft het implicaties die veel verder reiken dan deze eerste verkennende studie aldus de onderzoekers.

Al meer dan tien jaar wordt het verandering brengende potentieel van CAR-T-therapie beperkt door een fundamenteel knelpunt: de productie van de CAR-T cellen duurt lang en is erg duur. De benodigde leukafarese, gecentraliseerde productietijdlijnen, chemotherapie om eventueel aangetaste lymfklieren te behandelen en monitoring in het ziekenhuis leiden gezamenlijk tot vertragingen, kosten en klinische risico's, met name voor patiënten met een agressieve vorm van de ziekte die al vóór de infusie kunnen verslechteren.

Tegen deze achtergrond vertegenwoordigt deze studie geen stapsgewijze behandelingsverbetering, maar een verschuiving in produceren en toepassen van een behandeling: de in vivo generatie / ontwikkelen en produceren van CAR-T-cellen, waarbij het traditionele productieproces volledig wordt omzeild. Met als gevolg dat patiënten die hiervoor in aanmerking komen veel eerder een behandeling kunnen krijgen.

Het volledige studierapport is tegen betaling in te zien en gepubliceerd in Nature:

  • Article
  • Published: 

In vivo generation of anti-BCMA CAR-T cells in relapsed or refractory multiple myeloma: a phase 1 study

Nature Medicine (2026)Cite this article

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Abstract

In vivo chimeric antigen receptor (CAR)-T cell generation can bypass ex vivo manufacturing and lymphodepletion, potentially simplifying and accelerating access to cellular therapy; preliminary clinical experience supports feasibility and suggests preliminary efficacy. This phase 1, single-arm, open-label trial evaluated the safety and tolerability of ESO-T01, a nanobody-directed, immune-shielded lentiviral vector encoding a humanized anti-B cell maturation antigen (BCMA) CAR, in adults with relapsed or refractory multiple myeloma. ESO-T01 was administered as a single intravenous infusion of 0.2 × 109 transduction units without leukapheresis, ex vivo manufacturing or lymphodepleting chemotherapy. Five heavily pretreated male patients (median three prior lines) were consecutively enrolled and followed for a median of 6.0 months. The trial was stopped early in 2025, and no further enrollment was performed. The primary endpoint was safety and tolerability, and secondary endpoints included efficacy, pharmacokinetics and pharmacodynamics of ESO-T01. No dose-limiting toxicities occurred. All patients developed grade 3 or higher adverse events. Cytokine release syndrome occurred in four patients (three grade 3 and one grade 2) and was managed with corticosteroids, tocilizumab, or supportive care. The most frequent toxicities were transient cytopenias and reversible hepatic enzyme elevations, and three patients experienced grade 2 infections. One patient developed grade 1 immune effector cell-associated neurotoxicity and died from extramedullary lesion-related spinal cord compression. Preliminary antimyeloma activity was observed: four of five patients achieved objective responses, including three stringent complete remissions, with minimal residual disease negativity (10−5) in all evaluable responders (4/4) by day 60. These findings provide preliminary evidence on the feasibility and safety of in vivo CAR-T generation using an immune-shielded vector. ClinicalTrials.gov registration: NCT06791681.

Data availability

All primary data supporting the findings of this study are included in this article and its supplementary files. Extended data tables and figures, together with the supplementary information, provide patient-level data for safety, response, pharmacokinetic and immunophenotyping analyses as well as vector construct, integration site analyses and gating strategies.

The clinical datasets generated and analyzed during this study are not publicly available due to proprietary restrictions and to protect patient privacy and sensitive information. All individual-level clinical data have been deidentified and are stored on the secure data server of Tongji Hospital. Interested researchers may contact the corresponding author to request access to the datasets. Access requires completion of a data access agreement describing the intended research use; commercial or for-profit use is prohibited. After approval by the applicant’s institution and our institutional data access committee, deidentified individual participant-level data will be provided within 6 months after publication and will remain accessible for at least 5 years. The full trial protocol and the statistical analysis plan are provided in the supplementary materials.

All requests for data access should be directed to the corresponding author (cunrui5650@hust.edu.cn), and responses will be provided within 10 working days.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (82170223 to C.L.) and the Natural Science Foundation of Hubei Province (2024AFD421 to C.L.). We thank H. Mei for helpful discussions. We thank all clinical investigators, research nurses and study coordinators for their contributions. We also acknowledge the members of the independent data monitoring committee for their oversight. The study was supported in part by EsoBiotec, which provided the ESO-T01 vector and technical input. The funder had no role in study design, data collection, data analysis, data interpretation or writing of the report.

Author information

Author notes

  1. These authors contributed equally: Ning An, Di Wang, Peiling Zhang, Jishuai Zhang, Philippe Parone.

Authors and Affiliations

  1. Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Ning An, Di Wang, Peiling Zhang, Jianlin Hu, Yuhan Bao, Li Xu, Haitao Ruan, Ying Wan, Xinyu Wen, Yang Gao & Chunrui Li

  2. Shenzhen Pregene Biopharma, Shenzhen, China

    Jishuai Zhang

  3. EsoBiotec, Mont-Saint-Guibert, Belgium

    Philippe Parone

  4. Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Chunrui Li

  5. Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, China

    Chunrui Li

Contributions

C.L., N.A., D.W. and P.Z. contributed to the analyses and interpretation of the clinical data. J.Z. and P.P. contributed to the development of the ESO-T01 construct. C.L., D.W., P.Z. and J.Z. designed the clinical protocol. C.L., D.W., P.Z., L.X., H.R. and Y.W. contributed to the clinical treatments. N.A., J.H., X.W. and Y.G. collected and assembled data. N.A., C.L, P.Z. and Y.B. wrote the paper. C.L. directed the study and had final responsibility to submit for publication. All authors read and approved the final paper.

Corresponding author

Correspondence to Chunrui Li.

Ethics declarations

Competing interests

P.P. is employed by and owns stocks in EsoBiotec. J.Z. is employed by and owns stocks in Shenzhen Pregene Biopharma Company. The other authors declare no competing interests.

Peer review

Peer review information

Nature Medicine thanks Leo Rasche, Eric Smith and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Anna Ranzoni, in collaboration with the Nature Medicine team.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

multiple myeloma, botkanker, ziekte van Kahler, CAR-T celtherapie, ESO-T01, chemotherapie, leukafarese, complete remissies


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