Adoptive T cell immunotherapy based on tumor infiltrating lymphocytes is the most effective treatment for cancer of malignant melanoma. Tumor-infiltrating lymphocytes (TILs) for cancer immunotherapy is about that T cells can be removed from tumor samples taken from patients and multiplied in the lab by treating them with IL-2. Then the T cells are injected back into the patient for a treatment. The tumor infiltrating lymphocytes immunotherapy has demonstrated high overall response rates, resulting in cancer regression and prolonged survival in comparison to IL-2 and ipilimumab treatments.
The first clinical pilot study using Tumor-infiltrating lymphocytes was reported in 1988 for metastatic melanoma. The study was performed on 12 patients who were treated with variable doses and combination of Tumor-infiltrating lymphocytes, IL-2 and cyclophosphamide. The result demonstrated partial response in 2 patients and partial regression in 1 patient. Tumor specific cytolytic activity was observed in 5 patients. The study demonstrated the possibility of treating the patients with a combined approach. In another report published in same year, 20 melanoma patients were treated with Tumor-infiltrating lymphocytes and IL-2 preconditioned with a single dose of cyclophosphamide. Objective response was observed in 9 patients who did not receive IL-2 and 2 patients in whom previous IL-2 therapy failed. These initial reports indicated that Tumor-infiltrating lymphocytes treatment regimen may provide higher response rate in melanoma patients. In continuation of the above studies Rosenberg et al (1994) treated 86 patients of metastatic melanoma with autologus Tumor-infiltrating lymphocytes and high dose of IL-2. Overall objective response rate of 35% was observed in patients who received cyclophosphamide and 31% in those who did not. In another study by Rosenberg et al (2011) three sequential clinical trials were performed in which 93 patients (metastatic melanoma) were treated with lympho depleting preparative regimen (chemotherapy alone or chemo with 2Gy or 12Gy irradiation), autologous Tumor-infiltrating lymphocytes and IL2. Objective response rates by RECIST criteria in the three trials were 49%, 52% and 72%, respectively. Study showed that 22% of all patients achieved complete tumor regression and 19% of the patients were disease-free for more than three years.
Galon et al (2006) studied Tumor-infiltrating lymphocytes in large cohorts of human colorectal cancers by gene expression profiling and in situ immunohistochemical staining. The data analysis suggested that immunological parameters were better predictors of patient survival than the histopathological methods. Furthermore, in situ data analysis suggested that Tumor-infiltrating lymphocytes might act as a valuable prognostic tool in the treatment of colorectal cancer. Pages et al (2009) evaluated the treatments of cytotoxic (CD8) and memory (CD45RO) T cells in patients with early-stage colorectal cancer. The results gave valuable information regarding tumor recurrence and survival in patients with early-stage colorectal cancer.
Gingras et al (2015) critically reviewed the relationship between immunity and breast carcinoma. Mahmoud et al (2011) studied clinical outcome of the Tumor-infiltrating lymphocytes treatment in breast cancer patients. The results suggested that tumor-infiltrating CD8+ T lymphocytes had antitumor activity and could potentially be exploited in the treatment of breast cancer. Since there has been an increase in the use of molecular fingerprint analysis in the field of cancer research, standard prognostic, predictive and diagnostic parameters are ever changing. Continued research in Tumor-infiltrating lymphocytes can further our understanding in tumor immunotherapy and improve effectiveness of therapies.
Tumor-infiltrating lymphocytes have shown good effectiveness in treating melanoma and other multiple groups of malignancies such as breast and brain metastasis. Tumor-infiltrating lymphocytes for cancer immunotherapy. There have also been some clinical trials that failed to produce good results with Tumor-infiltrating lymphocytes. needs further in-depth investigations on combination approaches that can improve long term efficacies and reduce the cost to a more affordable level.
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