Universal CD20 CAR-γδ T cell therapy has been granted Fast Track designation by the US FDA. What are the advantages of γδ T cells?

April 21, 2022/eMedClub News/--On April 19, 2022, Adicet Bio announced that the U.
S.
FDA has granted its CD20-targeting allogeneic CAR-γδ T product candidate ADI-001 Fast Track designation, For the treatment of relapsed or refractory B-cell non-Hodgkin lymphoma (NHL)
.

ADI-001 is currently undergoing a dose-escalation Phase 1 clinical study to evaluate the safety and tolerability of ADI-001 for the potential treatment of NHL
.

Interim results of the study showed that 3 out of 4 evaluable patients achieved remission, including 2 complete remission (CR) and 1 partial remission (PR), no dose-limiting toxicity, graft-versus-host disease , Immune effector cell-associated neurotoxicity syndrome or grade 3 or higher cytokine release syndrome
.

 ▲ ADI-001 interim data summary (Image source: Adicet official website) Chen Schor, President and CEO of Adicet Bio, said: "The fast track designation obtained this time represents an important milestone in the clinical development of
ADI
-001.
Unique in that it is designed to target malignant B cells by exploiting naturally occurring innate and adaptive receptors on γδ T cells, with the added benefit of engineering an anti-CD20 CAR
.

We remain optimistic about the potential of this project and look forward to Report more data
from the Phase 1 clinical trial of ADI-001 in the first half of 2022.

” Adicet: Focused on allogeneic γδ T cell therapy Adicet Bio is a clinical-stage biotechnology company focused on discovery and development for cancer Therapeutic allogeneic γδ T cell therapy
.

Adicet has developed a proprietary and powerful cell technology platform to activate, engineer and expand γδ T cells
.

 ▲ Adicet’s γδ T cell-based cell therapy process (Image source: Adicet’s official website) In addition, Adicet has demonstrated that it can target by generating and validating high-affinity and high-specificity T cell receptor-like monoclonal antibodies (TCRLs) The intracellular proteome, these TCRLs against disease-specific antigens presented on the cell surface by MHC class I complexes, could be exploited to arm γδ T cells, as T cell linkers, and as ADCs
.

Adicet has also developed proprietary technology, Epitarget™, to identify and validate novel disease-specific peptide targets
.

 Natural Killer γδ T Cells γδ T cells are a component of lymphocytes (leukocytes) that are present in all human beings and account for approximately 1-5% of peripheral blood lymphocytes
.

As part of the immune system's innate response, the natural properties make it a promising therapeutic candidate
.

 Analysis of gene expression in 18,000 individual tumors from 39 different malignancies revealed that γδ T cells were the infiltrating immune cells most likely to be associated with a positive outcome
.

Researchers have shown that there are various types of γδ T cells, all with slightly different properties
.

 Currently, a major goal in the field of adoptive immunotherapy is the generation of tumor-reactive αβ T cells for patients with a variety of cancers
.

To promote the rapid generation of tumor-reactive αβ T cells, it has been proposed to use αβ T cells that express tumor-specific αβ TCRs or CARs
.

However, its efficacy can be reduced following loss/downregulation of antigen expression by malignant cells, which often occurs in response to selective pressure on the therapy itself
.

 Unlike αβ T cells, γδ T cells are not limited by this: once γδ T cells recognize alterations in physiological stress signals, they can respond very rapidly without the need for priming by antigen-presenting cells or clonal expansion in the lymphatic system
.

They can immediately kill transformed or infected cells, engage the conventional adaptive immune system or self-present antigens in order to initiate a fully developed systemic immune response
.

 The advantages of γδ T as a carrier for cell therapy also include: Innate cytotoxicity through many different mechanisms, antigen presentation and cytokine/chemokine release to activate a broader immune response; Through sensing of stress signals specifically expressed by cancer cells , γδ TCR can distinguish cancer cells from healthy cells
.

Completely safe for healthy cells and will not kill them even when introduced in very high numbers; γδ TCRs are not MHC (histocompatibility complex) restricted
.

This means that if the donor's γδ T cells are transferred to the patient, the γδ T cells will not recognize the patient's body as foreign and will not cause GvHD (graft-versus-host disease)
.

This makes them ideal for allogeneic therapy - which can be harvested from healthy donors, scaled to very high quantities, stored and frozen, providing an easily accessible starting material for the manufacture of a wide variety of products
.

 References: 1.
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