Universal CAR-NKT therapy announces the latest clinical data, still effective in CAR-T therapy for relapsed patients

April 28, 2022 / eMedClub News/--On April 25, 2022, Athenex announced the presentation of 1 of its generic CAR-NKT cell therapy KUR-502 at the ASTCT and CIBMTR Joint Conference on Transplantation and Cell Therapy.
Phase 1 clinical study (ANCHOR) data
.

The Phase 1 clinical study of KUR-502 was an open-label dose-escalation trial
.

NKT cells were isolated from the leukocyte product of an HLA-mismatched healthy individual, transduced with CAR, expanded ex vivo for 14 days (99.
8% NKT purity), and cryopreserved
.

Subjects were treated in an outpatient setting and received either 107 (DL 1) or 3 × 107 (DL 2) CAR-NKT cells per square meter of body surface area after debridement with cyclophosphamide/fludarabine
.

 The data published this time are from 7 evaluable patients, including 2 patients who had been prematurely assessed, 1 non-Hodgkin lymphoma (NHL), and 1 acute lymphoblastic leukemia (ALL): At 4 weeks During the evaluation, 1 NHL patient had stable disease (SD), the other ALL patient had progressive disease (PD), 2 patients had complete remission (CR) for more than 6 months, and 1 patient was still in CR at 34 weeks.
Excellent safety profile with two responses (1 CR and 1 PR) observed in patients who relapsed after autologous CAR-T therapy, without immune effector cell-associated neurotoxicity syndrome (ICANS) and CAR-NKT cell-induced grafts 2 ALL patients with host-versus-host disease (GvHD) developed grade 1 cytokine release syndrome (CRS) ▲ Phase 1 clinical data of KUR-502 NKT cells have great potential NKT cells are a heterogeneous innate T lymphocyte population, Mainly present in tissues such as the liver and bone marrow, and have some of the same markers as T cells and natural killer (NK) cells.
It is a group of special T cells with both T cell receptors (TCR) and NK cell receptors on the cell surface.
A subpopulation, which produces a large amount of cytokines, accounts for only about 0.
1% of peripheral blood T cells
.

Although they are found in relatively small numbers in the human body, they have more powerful functions than many other immune cells
.

 The most common type of NKT cells (type 1 NKT cells, also known as iNKTs) express a constant T-cell receptor (TCR) alpha chain that is highly conserved in both mice and humans
.

iNKT cells are strongly associated with cancer, their recognition is not restricted by tumor antigens and major histocompatibility complex (MHC), and they have the ability to target multiple types of cancer
.

 In addition, iNKT cells have multiple mechanisms to attack tumor cells, including direct killing of CD1d+ tumors, and immune assistance, including activation of NK cells, activation of dendritic cells (DCs) to stimulate cytotoxic T lymphocytes (CTLs), and tumor suppression.
associated macrophages (TAMs),
etc.

This makes it extremely attractive in the development of cancer immunotherapy
.

  ▲ Image source: Kuur Therapeutics official website is based on the many advantages of NKT cells and the positive results achieved by CAR cell therapy, so researchers are trying to develop CAR-NKT cells, combining the original advantages of NKT cells and the specificity of CAR therapy, better achieve tumor killing effect
.

 Compared with traditional CAR-T therapy, the biggest advantage of CAR-NKT cell therapy is that it is expected to achieve effective control of most solid tumors
.

Moreover, CAR-NKT cell therapy generally does not cause immune hypersensitivity
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However, after entering the body, the activity of NKT cells will gradually weaken, which will affect its therapeutic effect.
In order to maintain its activity in the human body, it needs to be continuously and regularly infused
.

  ▲ Advantages of spot CAR-NKT (Image source: Kuur Therapeutics official website) Based on the various advantages and application potential of NKT, more and more developers are conducting research on it
.

In fact, a new generation of anti-cancer technology based on NKT cells has been developed for many years
.

 As early as 2005, a team led by Zhang Minghui, director of the Institute of Cell Therapy of Tsinghua University, was pleasantly surprised to discover that this large immune cell has a very strong weapon and has specific and non-specific two-way anti-tumor effects, and is a super killer in the immune system
.

 Since 2010, Zhang Minghui has cooperated with the First Affiliated Hospital of Tsinghua University to recruit volunteers for clinical trials
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Patients with liver cancer, lung cancer, gastric cancer, and anterior mediastinal sarcoma have been treated with this technology, and good efficacy and survival data have been obtained
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Recommended reading: The world's first neuroblastoma patient completed CAR-NKT cell therapy, and the domestic team of Professor Zhang Minghui launched NKT-related clinical trialsYimai Hei TechnologyIn October 2018, a scientific research team from Imperial College London In their findings, published in the journal Cancer Cell, the researchers created a genetically engineered cell dubbed 'CAR19-iNKT' that targets both CD19 and CD1d, conferring aGVHD protection through the integrity of its iTCR, αGalCer and ATRA enhanced the responsiveness of CAR19-iNKT cells
.

 The results of the study showed that CAR19-iNKT eliminated all cancer cells in 60% of the mice, and in a mouse lymphoma model, 90% of the mice treated with CAR19-iNKT cells achieved long-term survival, while those receiving CAR -T-treated mice had a survival rate of only 60%
.

Recommended reading: Cell sub-issue: Super-powered natural killer cell CAR-iNKT, a more effective "spot" immunotherapy for cancerYimai Meng broke the news In September 2019, researchers at UCLA made a new progress, they Using genetically engineered human hematopoietic stem cells to generate iNKT cells for cancer therapy effectively inhibits tumor growth in mice with multiple myeloma and melanoma
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The findings were published in the authoritative journal Cell Stem Cell on September 5, 2019
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 Since hematopoietic stem cells are long-lived and self-renewing, this strategy of adoptive transfer of iNKT TCR genetically engineered HSCs into cancer patients has the potential to provide patients with a lifetime of therapeutic levels of iNKT cells
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Recommended reading: Cell sub-issue: Chinese scientists turn hematopoietic stem cells into iNKT cell factories, effectively inhibiting tumor growth in mice with multiple myeloma and melanomaYimai Hei Technology October 2020, "Nature Medicine" article published In the article titled "Anti-GD2 CAR-NKT cells in patients with relapsed or refractory neuroblastoma: an interim analysis", the interim phase 1 clinical data of GD2 CAR-NKT in the treatment of neuroblastoma (NB) were published
.

Of the 3 NB patients who received this therapy, 1 achieved objective remission and the bone metastases regressed
.

 Reference: https:// -in-relapsed-or-refractory-lymphoma-and-leukemia-at-the-2022-transplantation-and-cellular-tandem-meetings-of-astct-and-cibmtr/——List of recent popular events——▼April On the 28th, Focus on mRNA Industrialization: Consideration of Key Factors for Raw Materials and Purification Processes