Another frontier progress in cellular immunotherapy: the first CAR-Treg therapy has been administered to patients Yimaimeng broke the news

March 31, 2022/eMedClub News/--On March 29, 2022, Sangamo Therapeutics announced the completion of the first patient dosing in the Phase 1/2 STEADFAST clinical study of TX200
.

TX200 is the company's wholly-owned autologous chimeric antigen receptor-regulated T cell (CAR-Treg) cell therapy candidate for the prevention of immune rejection following HLA-A2-mismatched living-donor kidney transplantation
.

Kidney transplantation is the treatment of choice for patients with end-stage renal disease (ESRD) who otherwise must undergo long-term dialysis
.

It is estimated that approximately 21-26% of transplanted kidneys are HLA-A2 mismatched
.

To prevent graft rejection, transplant recipients require lifelong immunosuppressive therapy, which affects the body's immune system and is associated with a variety of side effects, including serious life-threatening infections, malignancies, cardiovascular disease, and other Increased risk of drug-related toxicity
.

 TX200 is designed to prevent renal rejection by reducing local inflammation and promoting graft immune tolerance
.

TX200 consists of autologous Treg cells engineered to express HLA-A2 CAR
.

This investigational cell therapy is being evaluated in HLA-A2-negative patients who received mismatched HLA-A2-positive kidneys
.

TX200 cells will localize to the graft and activate upon binding to the HLA-A2 antigen
.

Through their ability to modulate the immune system, TX200 cells can protect grafts from immune-mediated rejection and reduce or eliminate the need for lifelong treatment with immunosuppressants
.

 ▲ TX200 (Image source: TxCell) The STEADFAST study is a multi-center, open-label, single-dose escalation, phase 1/2 study.
The primary endpoint is to evaluate the safety and tolerability of TX200.
Key secondary endpoints include evaluation Effects of TX200 on acute graft-related outcomes and long-term safety outcomes, and evaluation of the pharmacodynamics and pharmacokinetics of TX200
.

 In the STEADFAST clinical study, each patient underwent leukapheresis to collect their white blood cells, and then Treg cells were isolated, genetically modified, and cryopreserved
.

The patient then underwent a living donor kidney transplant, and after a recovery period, the patient received personalized TX200 cell therapy
.

Therefore, patient dosing occurs several months after patient enrollment
.

Sangamo expects to inject the drug in the second patient in the STEADFAST study in mid-2022
.

 This study is the first step in a pipeline of CAR-Treg programs that, in addition to TX200, Sangamo is developing CAR-Treg cell therapy candidates in preclinical studies, including potential treatments for multiple sclerosis and inflammatory bowel disease
.

 Sandy Macrae, CEO of Sangamo, said: "We are very grateful to the patients and researchers who have participated in what we believe to be the first-ever CAR-Treg cell therapy candidates in humans
.

We believe CAR-Tregs are the next frontier in cell therapy.
field, representing solid organ transplantation and potentially transformative treatments for many challenging autoimmune and inflammatory diseases
.

CAR-Treg: Another Frontier of Cellular Immunotherapy CAR-Treg has great potential and is a leader in the treatment of immune diseases, because Treg (regulatory T cells) are a class of cells that control autoimmune reactivity in the body A subset of T cells, the traffic police of the body's immune system, can effectively instruct other immune cells when to activate and when to stop
.

It is mainly involved in suppressing the immune response, rather than attacking invaders, ensuring that the immune system does not harm by mistake Healthy organs, while also protecting the body from pathogenic microorganisms, play an important role
in preventing autoimmune system diseases.
CAR
-Treg is a Treg that expresses CAR through genetic engineering to precisely locate autoimmune and inflammatory pathological sites.
A hot spot of research in recent years.
In
July
 2018, Sangamo acquired TxCell in a cash transaction of 72 million euros ($84 million), and obtained the company's leading product candidate TX200, thus starting research in the field of CAR-Treg
.

Sangamo plans to combine its zinc finger nuclease gene editing technology (ZFN) with the CAR-Treg platform to develop safer and more effective treatments for a range of immunological and autoimmune disease indications
.

 In addition to autologous, Sangamo It is also working on the development of general-purpose CAR-Treg cell therapy
.

In April 2020, Mogrify Ltd (Mogrify®) and Sangamo Therapeutics signed a collaboration and exclusive license agreement, Sangamo will be based on Mogrify's patented induced pluripotent stem cells ( iPSCs) and embryonic stem cells (ESCs), as well as their own zinc finger protein (ZFP) genetically engineered CAR-Treg technology to develop allogeneic cell therapy
.

 Under the terms of the agreement, Mogrify will be responsible for discovering and optimizing the transformation technology from iPSCs or ESCs to Tregs, while Sangamo will be granted exclusive rights to generate Tregs from iPSCs or ESCs using Mogrify's technology
.

Sangamo hopes to use its ZFP genetic engineering technology and therapeutic development capabilities to convert these Tregs into new "off-the-shelf" allogeneic CAR-Treg cell therapy candidates, and hope to develop them clinically, and eventually register them as therapeutics, for Treatment of inflammatory and autoimmune diseases
.

 At the same time, many companies such as AZTherapies, Kyverna Therapeutics, Mogrify and others are actively focusing on this field
.

 AZTherapies acquired Smith Therapeutics, which owns the Treg core technology platform, in October 2019 to use the platform to develop engineered Treg cell therapies for the treatment of neurodegenerative diseases including Alzheimer's disease
.

At present, the company has developed a CAR-Treg therapy targeting brain glial cells with immunosuppressive function, which is currently in the preclinical research stage
.

 Kyverna Therapeutics' proprietary synReg T cell platform utilizes synthetic biology to reprogram T cells to generate CAR-Treg cells, which can specifically target diseased tissues and allow Treg cells to pass through various immunosuppressive mechanisms in diseased tissues.
Suppresses autoimmune diseases
.

In January 2022, Kyverna Therapeutics announced the completion of a $85 million Series B financing to accelerate the development of CAR-T and CAR-Treg for autoimmune diseases
.

 At present, most of CAR-Treg therapies are in the preclinical or early clinical stage, and it is expected that this cell therapy will show strong potential in subsequent clinical trials and benefit more patients as soon as possible
.

 References: 1.
https:// -treg-cell-therapy-tx200-in-kidney-transplantation/2.
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