One-stop CAR-γδ T Development Services

All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

γδ T cells have recently gained considerable attention as an attractive tool for cancer adoptive immunotherapy. Equipped with deep knowledge and experience in chimeric antigen receptor (CAR)-based therapy, Creative Biolabs offers high-quality CAR-γδ T cell solutions for our valued clients. Our experienced scientists work together to get your study launched quickly.

Fig.1 Selected γδ T cell therapies in development. (Garber, 2020)

Introduction

γδ T cells are the prototype of 'unconventional' T cells. γδ T cells are a relatively small subset of T cells in peripheral blood and the most abundant T-lymphocyte subset in some epithelial barriers. Because of their potent anti-tumor activity, γδ T cells have recently attracted much attention as effector cells for cancer immunotherapy. γδ T cells may offer an attractive chassis to drive anti-tumor responses that are not only broader, but also possess a more favorable safety profile. Advantages of γδ T cells as a suitable platform for CAR expression and allogeneic adoptive cell therapy:

γδ T cells show both adaptive immunity and innate immunity properties.
TCR activation of γδ T cells is non-MHC dependent.
γδ T cells express various NK cell receptors.
γδ T cells do not cause graft versus host reaction (GvHD).
γδ T cells show activation to acquire phenotype and properties of professional antigen-presenting cells (APCs).
Vγ9Vδ2 T cells can attack tumor cells through the recognition of phosphoantigens.

Fig.2 Functional advantages of γδ T cells for CAR-T cell cancer therapy. (Mirzaei, 2016)

Creative Biolabs' world-class teams have extensive experience in developing CAR-γδ T cells. With our full-service offering, we can construct the single-chain variable fragment (ScFv), transfer it into a CAR retroviral vector of your choice, make retrovirus, and transduce activated γδ T cells. For generated CAR-γδ T cell products, a broad range of in vitro and in vivo assays are available to assess their antitumor function. You can start at any module or choose end-to-end integrated services to best fit your projects within budget requirements.

Fig.3 Common workflow of CAR-γδ T development services. (Creative Biolabs)

Transduction Strategies

Viral-based techniques

Retrovirus has been widely used to transduce γδ T cells mainly due to the availability of packaging cell lines that can be stably transduced to produce high virus titer. Lentiviruses have a safer insertional profile. Compared to human immunodeficiency virus (HIV)-based vector, simian immunodeficiency virus (SIV) vector for transducing γδ T cells shows a higher transduction efficiency (42% vs. 65%).

Transposon-based techniques

The Sleeping Beauty Transposon system is more efficacious than lentiviral transduction. Cells must be electroporated for gene transfer to occur, but do not require a specific proliferative stimulus. Unlike proliferation-driven transduction techniques, there was no "skewing" of the γδ T cell population toward a particular Vγ/Vδ subset. Thus you can transfer a CAR gene into a polyclonal population of γδ T cells, and following the γδ T cell subsets sorting, you can harvest specific CAR-γδ T cell subsets.

mRNA-based transduction

Transient CAR expression strategies could reduce CAR-T cell toxicity. mRNA transfection using electroporation is used to generate γδ T cells expressing NKT cell-derived TCRs and an additional α/β TCR or a CAR specific for tumor antigens.

Our one-stop CAR-γδ T therapy development services include but are not limited to:

Creative Biolabs is dedicated to helping our clients design innovative solutions and develop CAR-γδ T therapies. You can click here to build your CAR. Please feel free to contact us with your requirements.

References

Garber, K. γδ T cells bring unconventional cancer-targeting to the clinic-again. Nature biotechnology. 2020, 38(4): 389-392.
Mirzaei, H.R.; et al. Prospects for chimeric antigen receptor (CAR) γδ T cells: A potential game-changer for adoptive T cell cancer immunotherapy. Cancer letters. 2016, 380(2): 413-423.