Table Info

Table 1.

Summary of published studies related to CAR expression in γδ T cells

Author	Gene expression	Cell population + expansion	CAR type	Targeting antigen	Cytokine production	Tumour targets	In vivo tumour model
Deniger et al., 2014 [16]	SB transposon	Whole polyclonal PBMCs + K562 aAPCs (CD19, CD64, CD86, CD137L, IL-15)	Second-generation CAR (28ζ)	CD19 (B-ALL)	TNFα IFNγ	▪CD19-EL4 (Mu T cell lymphoma) ▪NALM-6 (Hu B-ALL)	NALM-6 xenografts in NSG mice
Themeli et al., 2013 [17]	Lentivirus	T cells derived from iPSCs + 3T3-CD19 aAPCs	Second-generation CAR (28ζ)	CD19 (B-ALL)	TNFα IFNγ IL-2	CD19-EL4 (Mu T cell lymphoma)	CD19⁺ Raji Burkitt lymphoma (Hu) xenografts in NSG mice
Fisher et al., 2017 [19]	SFG retrovirus	Vδ2⁺ cells from CD56-depleted PBMCs + zoledronic acid	Second-generation CAR (28ζ) Third-generation DAP10 CCR	GD2 (NB)	TNFα IFNγ IL-2 IL-4 Granzyme B	▪Kelly (Hu NB) ▪SK-N-SH (Hu NB) ▪LAN-1 (Hu NB) ▪TC-71 (Hu Ewing sarcoma) ▪CT26-GD2 (Mu colonic carcinoma)	N/A
Harrer et al., 2017 [15]	RNA electroporation	▪PBMCs + zoledronic acid or anti-CD3 (OKT-3) ▪ MACS-isolated γ/δ⁺ T cells & CD8⁺ T cells + OKT-3	Second-generation CAR (28ζ) Melanoma-specific αβ TCR	▪MCSP (melanoma) ▪Melanosomal gp100 (melanoma)	TNFα IFNγ IL-2	▪T2A1 (Hu TXB hybridoma) ▪Mel526 (Hu melanoma) ▪A375M (Hu melanoma) ▪Daudi (Hu T cell lymphoma)	N/A
Capsomidis et al., 2018 [14]	SFG retrovirus	PBMCs + zoledronic acid or concanavalin A	Second-generation CAR (28ζ)	GD2 (NB)	N/A	▪SK-N-SH (Hu NB) ▪LAN-1 (Hu NB) ▪SupT1 (Hu lymphoblastic lymphoma)	N/A
Fisher et al., 2019 [31]	SFG retrovirus	PBMCs + zoledronic acid and IL-2 or anti-CD3 (OKT-3), anti-CD28 (28.2), and IL-2	Third-generation CAR (CD28ζ) Third-generation CD28 CCR Third-generation DAP10 CCR	▪GD2 (NB) ▪CD33 (AML) ▪ ErB2 (breast adenocarcinoma) ▪CD19 (B-ALL)	TNFα IFNγ	▪LAN-1 (Hu NB) ▪MV4-11 (Hu AML)	N/A
Ang et al., 2020 [34]	RNA electroporation	PBMC + zoledronic acid and IL-2 electroporated following expansion	First-generation (ζ) Second-generation (27ζ or 28ζ) Third-generation (28ζ-bb-ζ)	NKG2D	N/A	▪SW470 and HCT116 (colorectal) ▪SKOV3 (ovarian)	N/A
Fleischer et al., 2020 [35]	HIV-1 lentivirus	PBMCs + zoledronic acid and IL-2	Second-generation NSCAR (IL-2 SP + Myc tag) Second-generation NSCAR (IL-2 SP + CD8α hinge)	▪CD5 (T cell malignancies) ▪CD19 (B-ALL)	IFNγ	▪Jurkat (CD19⁻CD5⁺ T cell lymphoma) ▪Molt-4 (CD19^–CD5⁺ T-ALL) ▪697 (CD19⁺CD5^– B-ALL)	N/A
Rozenbaum et al., 2020 [18]	MSGV retrovirus	PBMCs + zoledronic acid and IL-2	Second-generation CAR (28ζ)	▪CD19 (B-ALL)	IFNγ	▪NALM-6 (Hu B-ALL) ▪CCRF-CEM (T-ALL) ▪Toledo (NHL) ▪K562 (CML)	NALM-6 xenografts in NSG mice

aAPCs: artificial antigen-presenting cells; PBMCs: peripheral blood mononuclear cells; IL-15: interleukin-15; DAP10: DNAX-activating protein 10; CCR: chimeric costimulatory receptor; B-ALL: B-cell acute lymphoblastic leukemia; N/A: not applicable; MCSP: melanoma-associated-chondroitin-sulfate-proteoglycan; NKG2D: natural killer group 2D

Declarations

Author contributions

GMF and JA shared equally in design and writing of the manuscript. All authors contributed to manuscript revision, read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

John Anderson receives funding from the NIHR Great Ormond Street Biomedical Research Centre and Gabrielle M. Ferry is in receipt of a PhD studentship funded by TC-Biopharm. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

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