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D'Souza et al. J Cancer Metastasis Treat 2022;8:28 https://dx.doi.org/10.20517/2394-4722.2022.51 Page 9 of 15
Figure 2. Schematic of novel CARs designed to enhance the efficacy of CAR-T cells in solid tumors. (A) CARs targeting two TAAs (dual
CAR expressing T cell); (B) tandem CARs (TanCARs) that have two different scFVs connected in tandem to one CAR T-cell and deal
with antigen escape or multiple tumor antigens; (C) armored CARs secreting cytokines, antibodies and other immunomodulatory
agents in the TME upon CAR-antigen engagement; (D) switchable CARs that utilize different target molecules specific for each TAA
and can redirect CAR-T cells against various types of tumors; (E) inhibitory CARs that, upon interaction with normal cells expressing
the TAA, prevent downstream signaling cascades inhibiting CAR-T cell function; (F) synNotch CARs, in which recognition of a specific
TAA (TAA1) on tumor cell through synNotch receptor, cleaves the receptor to release a transcription factor (TF) specific for the
induction and expression of a CAR against a second TAA (TAA2).
Induction of bystander effects following epitope spreading
CAR-T cell therapy for solid tumors, in which the targeted antigen is not expressed on all of the tumor cells,
could be more successful when combined with immunomodulatory agents that enhance bystander effects.
Bystander effects, in the context of CAR-T cells, refer collectively to the effects induced as a consequence of
