Re-Tooling of γδ T Cells for Cancer Immunotherapy Using Advanced Manufacturing and Genetic Engineering

TL;DR

This paper reviews the potential of γδ T cells for cancer immunotherapy and how genetic engineering and manufacturing can improve their effectiveness.

Contribution

The paper evaluates γδ T cells as a promising alternative to CAR T cells and discusses strategies to enhance their therapeutic potential.

Findings

Vδ2 cells are the main circulatory γδ T cell subtype.

Vδ1 cells show strong tissue tropism.

Genetic engineering and manufacturing can boost γδ T cell potency for cancer treatment.

Abstract

What are the main findings?
Vδ2 cells are the predominant circulatory subtype.Vδ1 cells are highly tissue tropic.

Vδ2 cells are the predominant circulatory subtype.

Vδ1 cells are highly tissue tropic.

What are the implications of the main findings?
Allogeneic γδ T cells are under development for cancer immunotherapyInnovative genetic engineering and manufacturing strategies may be used to boost potency.

Allogeneic γδ T cells are under development for cancer immunotherapy

Innovative genetic engineering and manufacturing strategies may be used to boost potency.

Adoptive immunotherapy using ex-vivo-amplified autologous αβ T cells has achieved notable success in the treatment of diverse cancer types. Pre-eminent among these developments has been the advent of chimeric antigen receptor (CAR) T cell therapy, which has revolutionised the treatment of selected haematological malignancies. However, autologous CAR T cell immunotherapy is poorly scalable and has demonstrated limited efficacy against solid tumours. Accordingly, there has been significant interest in alternative strategies that may bridge these gaps. The use of γδ T cells is an attractive alternative since they possess intrinsic anti-tumour activity and do not elicit graft versus host disease (GvHD) when employed as an allogeneic drug product. In this review, we evaluate the potential use of γδ T cells for cancer immunotherapy and how manufacturing and genetic engineering refinements can be used to potentiate this activity. We also summarise current clinical experience with CAR γδ T cell therapies and discuss the implications of these findings for the next generation of cellular immunotherapies.

Figures