Immunotherapy is one of the specific therapeutic
tools available for eradicating the tumors. Adoptive T-cell therapy is cell
based immunotherapy which redirects T-cells to specifically target tumors by
utilizing either engineered T-Cell Receptor (TCR) or engineered Chimeric
Antigen Receptor (CAR) against the antigens expressed by tumors 1. CAR
expressing T-cells have shown promising results for treating hematological
malignancies 2, 3, but their utility for treating the solid tumors is limited
4. There are number of challenges that decrease the efficiency of CAR-T cell
therapy. T-cell trafficking, T-cell infiltration and tumor immune-suppressive
environment are the major hurdles created by tumor in order to protect itself
from immune system 5. There are also other toxicities associated with CAR
T-cell therapy, Cytokine Release Syndrome (CRS) and On Target/Off-Tumor
toxicity 6. T-cells engineered with chimeric receptors that recognizes
antigens that are either specifically or abundantly expressed by the tumors, so
that CAR T-cells specifically recognize the tumors and destroy them. But
unfortunately the antigens that are employed to design the CAR are also
expressed by the normal tissues thus arising the On Target/Off-Tumor toxicity
7. Thus to improve the efficacy of the CAR T-cell therapy, antigens that are
specifically expressed by cancer cells must be utilized. Tumor Associated
Antigens (TAA) is the group of proteins that are exclusively expressed by
tumors and therefore can be utilized for constructing specific CARs.
Cancer-testis antigens come under the category of TAA that are expressed in
testis under normal conditions but their aberrant expression was observed in
the tumors 8. CT-genes being specific and immunogenic in nature can be used
as a potential immunotherapeutic target against cancer 9, 10, 11. Therefore
CT-antigens can be utilized for generating specific receptors that can be
utilized for engineering specific CAR T-cells. Such CAR T-cells can be much
more effective and can significantly reduce the On Target/Off-Tumor toxicity.

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