Cell Immunotherapy against Melanoma: Clinical Trials Review

Abstract

Melanoma is one of the most aggressive and therapy-resistant types of cancer, the incidence rate of which grows every year. However, conventional methods of chemo- and radiotherapy do not allow for completely removing neoplasm, resulting in local, regional, and distant relapses. In this case, adjuvant therapy can be used to reduce the risk of recurrence. One of the types of maintenance cancer therapy is cell-based immunotherapy, in which immune cells, such as T-cells, NKT-cells, B cells, NK cells, macrophages, and dendritic cells are used to recognize and mobilize the immune system to kill cancer cells. These cells can be isolated from the patient’s peripheral blood or biopsy material and genetically modified, cultured ex vivo, following infusion back into the patient for powerful induction of an anti-tumor immune response. In this review, the advantages and problems of the most relevant methods of cell-based therapy and ongoing clinical trials of adjuvant therapy of melanoma are discussed.

Comparative Evaluation of Anticancer Activity of Natural Methoxylated Flavones Xanthomicrol and Eupatilin in A375 Skin Melanoma Cells

“…In our experimental conditions, both compounds were not able to induce a 50% reduction in cell death at the concentrations tested, due to the short time of incubation (24 h), the high drug resistance of A375 melanoma cells [ 38 ], and the limits of cell tolerability for the vehicle used to dissolve the lipophilic flavones.…”

“…EUP showed lower cytotoxicity versus normal HaCaT skin keratinocytes than A375 cells in the range 2.5–25 μM, evidencing a certain selectivity towards skin malignant cells at low doses, as previously observed in 3T3 fibroblasts [ 14 ]. The absence of an elevated selective viability reduction in EUP and XAN in A375 cells compared to normal keratinocytes was probably attributable to the high drug resistance of melanoma cells [ 38 ]. A previous study evidenced the superior cytotoxic effect of the anticancer flavonoid luteolin (3,4,5,7-tetrahydroxy flavone) in HaCaT cells (IC 50 value of 37.17 μM) than in A375 cells (IC 50 value of 115.1 μM) after 24 h-incubation [ 53 ].…”

“…Starting from all these considerations, this manuscript aimed to investigate and compare for the first time the modulatory effect of EUP and XAN on the lipid profile in cutaneous melanoma cells. Melanoma is a skin cancer caused by the malignant transformation of melanocytes [ 38 ]. Cutaneous melanoma represents the most aggressive and deadliest type of skin cancer (accounting for 5% of total skin cancers), with an increasing incidence worldwide [ 39 , 40 , 41 ].…”

“…Cutaneous melanoma represents the most aggressive and deadliest type of skin cancer (accounting for 5% of total skin cancers), with an increasing incidence worldwide [ 39 , 40 , 41 ]. It is one of the most therapy-resistant types of cancer [ 38 ]; therefore, the development of new therapeutic approaches is strongly mandatory. Lipid metabolic dysregulations have been demonstrated to contribute to the phenotype plasticity of melanoma cells and/or melanoma aggressiveness [ 42 ].…”

Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling

“…Also, an adverse phenomenon of hyperprogression described in ICI therapy in solid tumors [ 212 , 213 ] is very rare in melanomas [ 214 ]. In the past, several immunotherapeutic approaches were tested, including the use of peptide from melanogenesis-related proteins, dendritic cells, tumor-infiltrating lymphocytes (TIL), adoptive T-cell therapy (ACT), interleukin 2, and interferons [ 215 , 216 , 217 , 218 ], none of which were sufficiently effective in phase 3 clinical trials [ 30 , 191 ]. Tumor-infiltrating lymphocyte (TIL) therapy for patients with advanced-stage melanoma have been reviewed in-depth recently [ 218 ].…”