. 2023 Jul 7;71(1):18. doi: 10.1007/s00005-023-00683-y

Table 2.

Main studies on in situ generated CAR cells

Gene transfer platform	Relevant results	References
Viral
Lentiviral vector CD8-LV	CD19-CAR-T cells generated in humanized mice specifically targeted human CD8⁺ cells and eliminated CD19⁺ B cells and Raji cells	Pfeiffer et al. (2018)
Lentiviral vector CD8-LV	CD19-CAR-T cells generated in humanized mice eliminated luciferase-encoding CD19⁺ Nalm-6 tumor cells from bone marrow and spleen of T cells transplanted NSG mice CAR⁺ NK and NKT cells were observed, which suggests a non-specific action of the vector	Agarwal et al. (2019)
Sindbis lentiviral vector with a bispecific antibody binder	A single dose of vector generated CAR⁺ T cells in a humanized mice injected with FFLuc BV-173 malignant B cells. These CAR-T cells suppressed CD19⁺ tumor cell growth and prolonged the overall survival time	Huckaby et al. (2021)
Adeno-associated viral vector	A single vector infusion into humanized mouse model of human T-cell leukemia reprogrammed T cells to express CAR. These CAR-T cells suppressed tumor growth CAR⁺ NK cells and CAR⁺ B cells were observed, which suggests a non-specific action of the vector	Nawaz et al. (2021)
Lentiviral vectors CD4-LV and CD8-LV	CD4-LV and CD8-LV vectors infusion selectively transduced human CD4⁺ and CD8⁺ T cells. These CAR-T cells contributed to tumor regression in mouse models	Zhou et al. (2012, 2015)
Non-viral
Poly (β-amino ester)-based NPs	NPs with encapsulated plasmids coding leukemia-specific 194-1BBz CAR and hyperactive iPB7 transposase selectively bound CD3⁺ lymphocytes. Cells after the transfection were functional, non-toxic, and underwent proliferation Nanoparticles reduced tumors in albino C57BL/6 mice	Smith et al. (2017)
Poly (β-amino ester)-based NPs	NPs delivering mRNA encoding CAR or TCR transfected human CD8⁺ T cells and reprogrammed circulating T cells to recognize leukemia in immunodeficient mice. NPs showed the antitumor activity in mice subcutaneously injected with LNCaP C42 prostate carcinoma cells and in HBV-induced HCC	Parayath et al. (2020)
Mannose-conjugated polyethylenimine NPs	NPs with encapsulated piggyBac vector coding anti-ALK CAR and generated ALK-CAR macrophages (M). To polarize cells from M2 into M1 phenotype, a gene coding IFN-γ was delivered to modified CAR-M. Transfected macrophages changed their phenotype to M1 and delayed the tumor growth in tumor-bearing mice NPs injection increased the number of activated CD8⁺ T cells and decreased CD4⁺CD25⁺FoxpP3⁺ regulatory T cells in the tumor	Kang et al. (2021)
LNPs	CD5-coated LNPs delivering mRNA encoding FAP selectively reprogrammed T cells into FAP-targeting CAR-T cells. CAR-T cells killed FAP-expressing cells in vitro and were capable of trogocytosis. 14 days after LNPs injection, left ventricular end diastolic and end systolic volumes were normalized in a mouse model of heart injury	Aghajanian et al. (2019); Rurik et al. (2022)