WRITTEN BY HITESHI PATEL

Through evolutionary processes, tumor cells have developed many mechanisms that aid in evading the detection of the immune system. For instance, tumors can downregulate the number of antigens (a harmful toxin) it produces as well as create an immunosuppressive microenvironment with the secretion of anti-inflammatory cytokines (small proteins important for cell signaling). Researchers have made significant progress in recognizing these evasion pathways and have developed a series of drugs that can recognize various immune checkpoints by targeting specific receptors such as the chimeric antigen receptor. Despite this progress, it is extremely difficult to determine what particular evasion mechanism a tumor might employ, consequently making it even harder to decide which drug to administer. 

This situation becomes even more serious when working with recurrent solid tumors that cannot be surgically resected and do not respond to chemo or radiation treatments. Given a tumor’s strong resistance to treatment, it is likely it is employing multiple evasion pathways, making treatment with drugs ineffective. There is, however, one solution that can be utilized in this situation. 

T-cell therapy is a highly specialized and targeted strategy that both saves healthy tissue around the tumor and harmonizes with other therapies simultaneously. T-cells, or cytokine-induced immune effector cells, are obtained by in vitro cultures from resected lymphocytes tumor tissue. These cells are then directed towards tumor-associated antigens (TAA) via the use of certain biomarkers. The therapy can not only shrink the tumor but also allows researchers to collect samples of various TAAs for further research. 

Despite all of these benefits, there are still various drawbacks to using T-cell therapies on live patients. Often, the T-cells can be too good at targeting TAAs and will attack healthy tissue that produces even the slightest amount of antigen. This can create weakness in the surrounding system, allowing the tumor to grow even larger. Furthermore, this weakening effect intensifies if the patient is pregnant during the administration of the therapy (Camoli 2019). It has been found that these T-cells interfere with fetal development, as this is an immune-privileged site in the body. In order to combat these obstacles, genomic studies are being conducted to sequence specific antigens and train the T-cells to only attack potentially harmful sequences.

Overall, T-cell therapy offers a promising alternative to conventional, harmful treatments of resistant or metastatic solid tumors. While some of the methodology needs to be refined before commercial use, T-cell therapy is likely to be one of the most widely used additional treatments for these tumors in the coming years.

Comoli, P., Chabannon, C., Koehl, U., Lanza, F., Urbano-Ispizua, A., Hudecek, M., … Pedrazzoli, P. (2019). Development of adaptive immune effector therapies in solid tumors. Annals of Oncology, 30(11), 1740–1750. doi: 10.1093/annonc/mdz285

Zafar, S., Akhter, S., Garg, N., Selvapandiyan, A., Jain, G. K., & Ahmad, F. J. (2020). Co-encapsulation of docetaxel and thymoquinone in mPEG-DSPE-vitamin E TPGS-lipid nanocapsules for breast cancer therapy: Formulation optimization and implications on cellular and in vivo toxicity. European Journal of Pharmaceutics and Biopharmaceutics, 148, 10–26. doi: 10.1016/j.ejpb.2019.12.016