Table 2.

Characteristics of the T-cell therapies available.

Method	System	Advantages	Disadvantages
Ex vivo expansion		No restricted by HLA type; small blood volume required; naïve donor can be used; generation of polyclonal T-cells	Extensive culture period; seropositive donors required
Direct Selection	pMHC multimer	No needed extensive ex vivo manipulation and undergo rapid expansion in vivo	Restricted by HLA type and streptamer; seropositive donors required; high frequency of specific T-cells needed; select for a limited repertoire of CD8+ cells
	Cytoquine capture	No needed extensive ex vivo manipulation and undergo rapid expansion in vivo; not restricted by HLA type; isolation of polyclonal CD4+ and CD8+ cells	Requires seropositive donors; large blood volumes needed
	Activation marker	Rapid detection and enrichment of T-cells; broader repertoire of antigen-specific T-cells; Compatible with other assay formats; not restricted by HLA; not needed previous information of immunodominant epitopes; no specialized APC such as dendritic cells are needed	Time-consuming and difficulty to isolate and expand functional cells; identification of novel T-cell epitopes often requires screening of a high number of epitopes
Genetically engineered cells	CAR-T	Recognize antigens in an HLA-independent manner; target conserved and essential epitopes; infused to a broad range of patients irrespective of HLA	Only surface antigens can be targeted; restricted by epitope; expensive; Several toxicities
	TCR-T	Wider range of targets; high affinity for specific antigens through genetic engineering; strong activation when a small amount of antigen is present; use of natural T-cell signaling mechanisms	Expensive; time- and labor-consuming; MHC restricted and depends on presentation by MHC molecules to recognize targets and activate T cell function; risk of hybridization (mismatch) between exogenous and endogenous chains