Therapy with TCR-engineered T cells is highly potent but reactivity outside tumor needs to be minimized whereas T cell trafficking inside tumor needs to be maximized.

T cell target antigens need to show absent expression in a multitude of healthy tissues, including all vital organs.

Recognition motif (derived from cognate peptide) of therapeutic TCR needs to be absent from endogenous proteins.

Defects in intra-tumoral accumulation of CD8 T cells are categorized according to entry, migration, and local activation of T cells.

Tumor micro-environment can be sensitized to enhance numbers of CD8 T cells with use of gene-engineering techniques or drugs with clinical precedent.