One-Stop CAR-γδ T Development Services

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 γδ T cells modulation using different substances.^1,3

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 The tumor cell recognition of CAR-γδ T cells.^2,3

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:

• Activation and expansion of γδ T Cell services
• CAR Design & Construction
• CAR Gene delivery services
• Isolation of CAR-γδ T cell services
• γδ T Cell subsets sorting services
• CAR-γδ T functional assay services
• NSCAR-γδ T Cell Development Services

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

1. Yazdanifar, Mahboubeh, et al. "γδ T cells: the ideal tool for cancer immunotherapy." Cells 9.5 (2020): 1305.
2. Lee, Derek, et al. "Human γδ T cell subsets and their clinical applications for cancer immunotherapy." Cancers 14.12 (2022): 3005.
3. Distributed under Open Access license CC BY 4.0, without modification.