. 2021 May 13;12:690565. doi: 10.3389/fimmu.2021.690565

Table 2.

Current challenges, reasons and possible solutions of TCR-T induced by T-iPSCs for the treatment of Hepatocellular Carcinoma.

Challenges	Reasons	Possible solutions
Security	Off-target effects	Find neoantigens
Security	Targeted toxicity	Find neoantigens
TCR mismatch	The introduced TCR chains match the endogenous TCR chains	A single viral vector encoding two TCR chains
TCR mismatch	The introduced TCR chains match the endogenous TCR chains	Gene knock-out
Tumor immune evasion	Loss of autoantigen	Find neoantigens
	Loss of HLA molecules
	Change of tumor antigen
	Monoclonal TCR-T
T cell depletion	LAG-3 and PD-1 overexpression	Gene knock-out
T cell depletion	LAG-3 and PD-1 overexpression	Targeted drugs
Problems with T cell homing	Nitration of CCL2 chemokines	Regulating the expression of chemokines
Problems with T cell homing	T cell surface glycoprotein changed	Regulating the expression of chemokines
Liver autoimmune suppression	Regulatory myeloid populations maintain liver immune tolerance	Improve the immune microenvironment

TCR, T Cell Receptor; TCR-T, T cell receptor T-Cells; HLA, human leukocyte antigen; LAG-3, Lymphocyte activation gene-3; PD-1, Programmed Death-1; CCL2, chemokine ligand 2.