Sheba Medical Center, Tel HaShomer ABC Advanced Biotherapy Center

Esensten Lab

We do translational research. Our goal is to bring new cell and gene therapies from the research lab to our patients.

We use the tools of synthetic biology, AI, robotics, and automated manufacturing platforms. When used together, these tools result in improved quality and broader access to life-saving medicines.

Jonathan H. Esensten, MD, PhD Director, Advanced Biotherapy Center, Sheba Medical Center Medical Director, Clinical Laboratories, Sheba Medical Center Senior Lecturer, Reichman University

Dr. Jonathan Esensten is a US-trained pathologist and immunologist with a 360-degree view of the science, medicine, and business of cell and gene therapy.

Dr. Esensten directs the Advanced Biotherapy Center (ABC) at Sheba Medical Center, an academic development and manufacturing laboratory for a wide range of cell, gene, and tissue-based therapies. He is a team leader for cellular therapy product development, manufacturing, and clinical trials, leading projects with academic, major-pharma, and smaller-biotech partners.

His work includes building the GxP systems (quality assurance, quality control, and regulatory programs) that cellular therapies depend on, with hands-on experience in IND submissions and interactions with the U.S. FDA, as well as experimental drug submissions to the Israel Ministry of Health.

Before Sheba, he directed cell and gene therapy development at the University of California, San Francisco (UCSF) from 2016–2022 and served as medical director of the blood bank at San Francisco General Hospital. He trained in cellular immunology, clinical pathology, and transfusion medicine at UCSF, with a PhD in immunology under Jeffrey Bluestone and postdoctoral work with Wendell Lim.

Today he also serves as Medical Director of the Clinical Laboratories at Sheba and holds a research-track faculty appointment at Reichman University's Dina Recanati School of Medicine.

MD/PhD, UCSF AB, Harvard ABPath · Clinical Pathology ABPath · Blood Banking / Transfusion Medicine 28 publications · 1 patent
Team

The people behind the science.

Under construction. Team profiles coming soon.
Research program

Engineering cells, and the systems that make them.

The lab works across the full arc of new therapy design, process development, GMP manufacturing, analytic development, and clinical trial execution.

Engineered T-cell therapeutics

Designing and building T-cell therapies, including CAR-T and regulatory T-cell (Treg) products, that harness synthetic biology to treat cancer, autoimmunity, and rare genetic disease. This work spans costimulation biology, non-viral genome engineering, and gene-corrected Treg therapy for inborn errors of immunity.

CAR-TRegulatory T cellsGenome editingSynthetic biology

Automated & robotic GMP manufacturing

Advancing closed, automated, and robotic platforms that make cell and gene therapies more reproducible, scalable, and affordable, from closed bioreactors for CAR-T production to robotic clusters for fully automated manufacturing. The goal is to shorten the distance between a promising therapy and the patients who need it.

Closed systemsRobotic automationProcess developmentScale-out

Translational & regulatory science

Moving therapies from bench to clinic through rigorous process development and regulatory strategy. The lab has led first-in-human cell therapy manufacturing and multiple experimental drug submissions (IND/IMPD) to the FDA and the Israel Ministry of Health, including an international collaboration to bring CAR-T therapy to South America.

IND / IMPDFirst-in-humanFDA & MOHGlobal access

Transfusion & laboratory medicine

Grounded in clinical practice: medical oversight of the full spectrum of laboratory and transfusion services. This includes evidence-based transfusion in trauma and critical care, convalescent plasma programs, and training the next generation of laboratory physicians.

Transfusion medicineClinical pathologyBlood banking
Clinical pipeline

From target to trial: our cell therapy pipeline at Sheba.

The lab is advancing a portfolio of CAR T-cell programs, from open, actively enrolling clinical trials to candidates in late and early preclinical development.

Program
Early preclinical Late preclinical Clinical trial
SHB-02-CD19
CD19 CAR T-cell therapy
Open · enrolling NCT07503353
SHB-04-CD22
CD22 CAR T-cell therapy
Open · enrolling NCT07135466
CD7 CAR
CD7 CAR T-cell therapy
Late preclinical
Allogeneic CD19 CAR
Allogeneic, CRISPR-edited CD19 CAR
Late preclinical
CD19/20/22 CAR
Multi-target CD19/CD20/CD22 CAR
Early preclinical
BCMA/GPRC5D CAR
Dual BCMA/GPRC5D CAR
Early preclinical
GMP facilities

Designing, building, and running the facilities that make cell & gene therapies.

Dr. Esensten has longstanding, hands-on expertise in the design, construction, and operation of GMP facilities for cell and gene therapy. He has directed academic GMP facilities on two continents, working with pharma, biotech, and academic partners to bring first-in-human trials from the cleanroom to the clinic, and has advised many international groups on building and operating GMP facilities of their own.

HICTF & GMP Facility

University of California, San Francisco

As Medical Director from 2016–2022, Dr. Esensten led UCSF's Human Islet and Cellular Transplantation Facility, an FDA-registered cGMP facility that has manufactured investigational cell therapies for over 20 years, supporting more than a dozen early-phase trials of T-cell, regulatory T-cell, and islet-cell products for academic, collaborating, and industry sponsors.

ABC–Wohl Facility

Advanced Biotherapy Center, Sheba Medical Center

As Director, Dr. Esensten leads the ABC–Wohl GMP facility at Sheba, a modern cleanroom suite, rebuilt and expanded under his direction, that manufactures cell, gene, and tissue therapies for clinical trials with academic, pharma, and biotech partners, built and operated to international GMP standards under Israel Ministry of Health regulation.

Clinical & education

Laboratory medicine, transfusion medicine, and training the next generation.

Alongside the lab, Dr. Esensten practices and teaches clinical laboratory and transfusion medicine, and is an experienced medical educator, from residents and fellows to medical students preparing for their board exams.

Laboratory medicine

As Medical Director of the Clinical Laboratories at Sheba Medical Center, Dr. Esensten provides medical oversight and advisory responsibility across the full spectrum of laboratory services. He is board certified in Clinical Pathology by the American Board of Pathology and holds Israeli Medical Specialist certification in Clinical Laboratory medicine.

Transfusion medicine

A fellowship-trained transfusion medicine specialist, he previously served as Medical Director of the blood bank at San Francisco General Hospital and chaired its Transfusion Committee, setting transfusion policy across the San Francisco health system and developing new blood-based therapies. He is board certified in Blood Banking / Transfusion Medicine.

Medical education & mentorship

He has taught laboratory and transfusion medicine to medical students, residents, and clinical fellows, served as Associate Fellowship Director of the UCSF Cellular Therapy / Transfusion Medicine Fellowship, and established new fellowship programs at UCSF and Sheba, including the first laboratory medicine fellowship in Israel. He lectures medical students at the Dina Recanati School of Medicine.

USMLE exam coaching

Dr. Esensten has spent hundreds of hours tutoring medical students for the USMLE Step 1, 2, and 3 examinations, coaching future physicians on both exam content and test-taking strategy.

Selected publications

Peer-reviewed work.

A selection from 28 peer-reviewed publications spanning T-cell biology, cell-therapy manufacturing, and transfusion medicine.

2025
Gene-corrected regulatory T cell therapy for IL2RA deficiency
Ha AS, Kalter N, … Shy BR, Esensten JH
Molecular Therapy
2024
A roadmap for affordable genetic medicines
Kliegman M, Zaghlula M, Abrahamson S, Esensten JH, … Doudna JA
Nature
2024
Development of a robotic cluster for automated and scalable cell therapy manufacturing
Melocchi A, Schmittlein B, … Esensten JH
Cytotherapy
2023
High-yield genome engineering in primary cells using a hybrid ssDNA repair template and small-molecule cocktails
Shy BR, Vykunta VS, … Esensten JH, Eyquem J, Marson A
Nature Biotechnology
2021
Polyclonal regulatory T cell manufacturing under cGMP: a decade of experience
Balcerek J, Shy BR, … Tang Q, Esensten JH
Front. Immunology
2018
Reprogramming human T cell function and specificity with non-viral genome targeting
Roth TL, Puig-Saus C, … Esensten JH, … Marson A
Nature
2017
Engineering therapeutic T cells: from synthetic biology to clinical trials
Esensten JH, Bluestone JA, Lim WA
Annu. Rev. Pathology
2016
CD28 costimulation: from mechanism to therapy
Esensten JH, Helou YA, Chopra G, Weiss A, Bluestone JA
Immunity
2013
CD28-inducible transcription factor DEC1 is required for efficient autoreactive CD4+ T cell responses
Martínez-Llordella M, Esensten JH, … Bluestone JA · co-first author
J. Exp. Medicine
Consulting & advisory

Advising the companies building the future of cell & gene therapy.

Dr. Esensten provides fractional and advisory support to biotech companies, bringing hands-on expertise in cell-therapy development, GMP manufacturing, and regulatory strategy.

Dr. Esensten works with organizations across the cell and gene therapy ecosystem, from manufacturing-technology companies to clinical-stage therapeutics developers. Engagements range from scientific advisory board membership to focused guidance on process development, GMP operations, and FDA / regulatory submissions.

Advisory work is conducted independently and is distinct from his academic and clinical roles at Sheba Medical Center.

Areas of focus

Independent advisory engagements
  • Cell & gene therapy development strategy
  • GMP manufacturing & process development
  • Regulatory strategy (FDA, EMA, Israel MOH)
  • Scientific advisory board service

Scientific Advisory Board & advisory roles include:

Multiply Labs

Robotic "physical AI" that links a facility's existing GMP instruments into a sealed, self-running system for manufacturing advanced therapies.

Limula

A unified, closed platform that combines bioreactor and centrifuge functions in a single automated device for cell and gene therapy manufacturing.

Exthymic

Cell therapy company developing technologies to manage patient variability and enable local production of therapies such as CAR-T.

Get in touch.

For collaborations, trainee inquiries, speaking, or advisory engagements.
Email
Laboratory
Advanced Biotherapy Center
Sheba Medical Center, Tel HaShomer, Israel
Academic appointment
Dina Recanati School of Medicine,
Reichman University
Sheba Medical Center, Tel HaShomer, Advanced Biotherapy Center
Reichman UniversityDina Recanati School of Medicine