It is worth noting that not only diversified TAAs are expressed in one kind of cancer, but also one TAA is expressed in multiple kinds of cancers. For example the NY-ESO-1 is highly expressed in melanoma, multiple myeloma, NSCLC, synovial sarcoma, breast cancer, renal cell cancer, hepatocellular cancer, esophageal cancer, ovarian cancer, bladder cancer, etc [ 52 - 54 ]. Similarly, the mesothelin is highly expressed in mesothelioma and breast cancer, cervical cancer, pancreatic cancer, ovarian cancer, lung cancer and endometrial cancer [ 55 ]. Table 2 and Figure 3 provide a good illustration of the multi-dimension interaction. Particularly, when GE-T specifically binds and kills tumors, we cannot ignore that these targeted TAAs may be normally or restrictedly expressed in multiple normal tissues. The multidimensional interactions make the potential toxicity of "on target, off tumor" unavoidable. For instance, the prostate-specific membrane antigen (PSMA) is expressed in prostate cancer, bladder carcinoma, schwannoma, tumor neovasculature of many solid tumors. But it was expressed in not only prostatic acinarcells but also many other normal tissues, including the kidney, small intestine, the central and peripheral nervous system, as well [ 56 ].
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