Modifying γδ T cells for cancer treatment: a systematic review

Abstract

Background: γδ T cells have the potential to became a competitive tool in cancer treatment, particularly through combined therapy and modifications. The objective of this review is to provide a more intuitive overview of the preclinical results of current γδ T cell-related modifications and to gain a general understanding of the quality of these studies.

Methods: A search of PubMed was conducted up until November, 2023 for studies applying γδ T cell-related modifications, including the utilization of only γδ T cell membrane receptors. I designed a set of questions and adapted the SYRCLE’s RoB tool to assess the integrity and risk of bias of the reviewed studies. Data on experimental methods, disease models, and cytotoxic efficacies were extracted and summarized.

Results: From the initial 4412 records, 73 studies were included, spanning a period from 2004 to 2023. The most commonly utilized strategies among the reviewed studies were chimeric antigen receptor (CAR)-T cell, T cell receptor (TCR)-T cell, and therapeutic antibodies. For cell modification, the most common method was retroviral transduction on PBMCs. The standard procedures typically involved stimulation, transduction, and expansion. The most common cell culture medium used was RPMI 1640 supplemented with fetal calf serum (FCS) and IL-2 or human AB serum and IL-2. Based on the questions I utilized for assessment, there were no significant differences in the quality of articles across these three strategies.

Conclusion: This review provided a general understanding of the methodology and preclinical efficacy of current γδ T cell-related modification studies in an intuitive way. In the meantime, the questions designed to assess the integrity and risk of bias in preliminary studies can serve as a checklist for improving the overall quality of future literature phrasing. This will ultimately minimize the unnecessary time and effort waste and expedite the translation of research to clinical practice.