Introduction
Cancer is one of the major leading causes of death all around the world. T cells are an essential part of the immune system and can be used to prevent and fight off cancer. Malignant transformation is a process that is caused by the rapid mutation of a normal cell that takes a long time to completely undergo. This led to tumor progression being spread to the cells and caused an accumulation of point mutations, chromosomal translocation, small-scale insertion, and deletions, etc. (Platsoucas, 2020a).
Mutations can be present in both cancer and normal cells (Platsoucas, 2020a). For example, point mutation causes a transformation of a gene, and mutations are caused by the breakage of DNA (Platsoucas, 2020a). Due to the transformation that results in the expression of tumor antigens, these cancer cells have become modified self-cells that are now can be identified and killed by the immune system (Platsoucas, 2020a). There is only one type of tumor antigens that can only be found in tumor cells, Tumor-Specific Antigens (TSA). Tumor-Associated Antigens (TAA) are shown at different stages of development and concentrations. TSA is caused by point mutation or other mutations only present in cancer cells (Platsoucas, 2020a). These are normally found in intracellular proteins because of the transformation of cell and chromosomal translocation of a cell. T cells in general recognize peptides in association with Major Histocompatibility Complex (MHC) antigens that are only shown on the surface of cells. This is because T cells don’t recognize soluble antigens unless they are small peptide fragments (Platsoucas, 2020b). MHC encodes for glycoproteins cells (Platsoucas, 2020b).
Hypothesis
The hypothesis to be tested in this paper is to determine whether patients who have metastatic synovial cell sarcoma or melanoma that express NY-ESO- 1 could effectively treat cancer cell regression with autologous TCR-transduced T cells.
Major Findings
In this study, all of the patients with NY-ESO- 1+ metastatic synovial cell sarcomas received nonmyeloablative chemotherapy followed by a median of T cells transduced with an anti-NY-ESO- 1 TCR (Robbins et al., 2014, p. 1020). The patients with synovial cell sarcoma age ranged from 19-65 years an about an equal number of males (ten) to females (eight) while patients with melanoma age ranged from 30-65 years old with the majority of the patients being male with only one fourth (5/20) being female (Robbins et al., 2014, p. 1020). The overall findings propose that the use of TCR-transduced T cells against the antigen NY-ESO- 1 to mediate cancer cell regression in the patients with synovial cell sarcomas and melanomas (Robbins et al., 2014, p. 1020). The experiment resulted in eleven of the 18 patients with synovial cell sarcoma resulted in an objective response based on the Response Evaluation Criteria in Solid Tumors (RECIST) (Robbins et al., 2014, p. 1020). Except for one patient, there was a response that occurred during the first treatment. The patient only displayed a partial response that only lasted for six months. Followed by two separate infusions of TCR-transduced T-cells there was still only a partial response to the treatment. Of the melanoma patients, eleven of the patients also expressed varied responses to the first treatment. Four of the patients had a complete response while two failed to respond at all to the infusion (Robbins et al., 2014, p. 1020). The patients who received partial responses that lasted for 3 to 28 months ended up having to be censored due to the development of unrelated cancer (Robbins et al., 2014, p. 1020). Based on the CT scans that demonstrate tumor regression that depicts before and after treatment with NY-ESO- 1 TCR T cells after 9-52 months (Robbins et al., 2014, p. 1020). There were multiple liver and lung lesions were regressed in the patients following the adoptive T-cell transfer. The four patients who were vaccinated with recombinant AVIPOX-ESO virus exhibited clinical responses to the adoptive transfer of T cells transduced with anti-NY-ESO-1 after three months (Robbins et al., 2014, p. 1020). This finding was determined to be insignificant due to the limited about of patients who received that treatment. This is because of only a total of 18 synovial cell sarcoma and a total of 20 melanoma patients based on those clinical responses. Major attempts were made to determine if there were factors that correlate to therapy mediated by the NY-ESO- 1 TCR, but there was no significant difference found in the number of T cells in patients with synovial cell sarcoma and melanoma (Robbins et al., 2014, p. 1020). The culmination of the results from the sarcoma and melanoma patients showed that clinical responses were linked to higher numbers of given T cells (Robbins et al., 2014, p. 1020). It was also found that in the peripheral blood of patients their percentage of CD8+ and NY-ESO-1+ T cells after transfer varied from 1% and 72% however, the median percentage of responder and non-responder was 8% and 6.5% (Robbins et al., 2014, p. 1020).
When experimenting there is always a possibility for errors during the experienced hence why there are multiple trials or data points for an experiment. When dealing with human subjects’ ethics plays a role in the human subject picking processes. For this experiment, there were no potential conflicts of interest disclosed by the other authors. However, it was noted that a male 40-year-old patient, who was administered T cells developed sepsis and died three days later (Robbins et al., 2014, p. 1020). In another trial, two patients died because of severe neurologic toxicity. This was due to the adoptive transfer of autologous PBMC transduced with a MAGE-A3-reactive TCR (Robbins et al., 2014, p. 1020).
References
Platsoucas, C.D. (2020a). Cancer Immunology Immunotherapy: Mobilizing the T Cells of the Body to Fight Cancer, pp.3-9.
Platsoucas, C.D. (2020b). The Cells of the Immune System: T cells, B cells, and Antigen-presenting Cells (APC), pp.54-55.
Robbins, P. F., Kassim, S. H., Tran, T. L. N., Crystal, J. S., Morgan, R. A., Feldman, S. A., Yang, J. C., Dudley, M. E., Wunderlich, J. R., Sherry, R. M., Kammula, U. S., Hughes, M. S., Restifo, N. P., Raffeld, M., Lee, C.-C. R., Li, Y. F., El-Gamil, M., & Rosenberg, S. A. (2014). A Pilot Trial Using Lymphocytes Genetically Engineered with a NY-ESO-1-Reactive T-cell Receptor: Long-term Follow-up and Correlates with Response. Clinical Cancer Research, 21(5), 1019–1027.