Nanomedicine to modulate immunotherapy in cutaneous melanoma (Review).
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ABSTRACT:
SUBMITTER: Volovat SR
PROVIDER: S-EPMC8014970 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In a relatively short period of time, treatment strategies for metastatic melanoma have radically changed leading to an unprecedented improvement in patient survival. In this period, immunotherapy options have evolved from cytokine?based approaches to antibody?mediated inhibition of immune checkpoints, cancer vaccines and pharmacological modulation of the melanoma microenvironment. Combination of immunotherapy strategies and the association of immune checkpoint inhibitors (ICIs) with BRAF V600 targeted therapy show encouraging results. The future of drug development in this field is promising. The comprehension of primary and acquired resistance mechanisms to ICIs and the dissection of melanoma immunobiology will be instrumental for the development of new treatment strategies and to improve clinical trial design. Moreover, biomarker discovery will help patient stratification and management during immunotherapy treatment. In this review, we summarize landmark clinical trials of immune checkpoint inhibitors in advanced melanoma and discuss the rational for immunotherapy combinations. Immunotherapy approaches at early stage of clinical development and recent advances in melanoma immunotherapy biomarker development are also discussed.
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Project description:Cutaneous melanoma remains a severe public health threat, with annual incidence increasing slowly but steadily over 4 decades. While early-stage melanomas can typically be treated with complete surgical excision with favorable results, the development of metastatic cancer, which is related to a lower survival rate, is linked to the primary tumor's rising stage and other high-risk features. Even though the first discoveries of an immunological anti-tumor response were published about a century ago, immunotherapy has only been a feasible therapeutic option for cutaneous melanoma in the last 30 years. Nonetheless, for the treatment of various cancers, including metastatic melanoma, the area of cancer immunotherapy has made significant progress in the last decade. As a result, melanoma continues to be the subject of several preclinical and clinical investigations to further understand cancer immunobiology and test different tumor immunotherapies. Immunotherapy's resistance to radiation and cytotoxic chemotherapy is one of its most distinguishing features. Furthermore, the discovery of biomarkers will aid in patient stratification and management during immunotherapy treatment. In this article, we discuss current knowledge and recent developments in immune-mediated therapy of melanoma.
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Project description:In the last few years, there has been a twist in cancer treatment toward immunotherapy thanks to the impressive results seen in advanced patients from several tumor pathologies. Cutaneous melanoma is a highly mutated and immunogenic tumor that has been a test field for the development of immunotherapy. However, there is still a way on the road to achieving complete and long-lasting responses in most patients. It is desirable that immunotherapeutic strategies induce diverse immune reactivity specific to tumor antigens, including the so-called neoantigens, as well as the blockade of immunosuppressive mechanisms. In this review, we will go through the role of promising monoclonal antibodies in cancer immunotherapy with immunomodulatory function, especially blocking of the inhibitory immune checkpoints CTLA-4 and PD-1, in combination with different immunotherapeutic strategies such as vaccines. We will discuss the rational basis for these combinatorial approaches as well as different schemes currently under study for cutaneous melanoma in the clinical trials arena. In this way, the combination of "push and release" immunomodulatory therapies can contribute to achieving a more robust and durable antitumor immune response in patients.
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Project description:WM164, a human melanoma line, was a gift from Dr M. Herlyn (Wistar Institute, Philadelphia, PA, USA). The cells were cultured using DMEM media supplemented with 10% serum (fetal bovine serum while growing cells and charcoal-treated serum during incubation with vitamin D compounds), 1% antibiotics and 5 g/mL insulin (Sigma-Aldrich, St. Louis, MO, USA). Cells were cultured in 75 cm2 plastic bottles (TPP–Techno Plastic Products AG, Trasadingen, Switzerland) with a filter in an incubator at 37 C with 5% CO2. CRISPR/Cas Knock out of the VDR. The clustered regularly interspaced short palindromic repeats (CRISPR) genetic engineering method was carried out to knock out VDR expression in the WM164 cell line as described in (Cancers 2021, 13, 3111. https://doi.org/10.3390/cancers13133111). The resulting cells with the VDR gene knocked out are designated as WM164 VDR KO, and the cells transduced with an “empty” lentivirus served as a control (WM164 scramble). VDR expression was checked for scramble and VDR KO lines before experiments were performed and further every 4 months after lentivirus treatment to ensure that VDR was not expressed in the WM164 KO. Sources of Vitamin D3 Compounds: Both 1,25(OH)2D3 and 25(OH)D3 were purchased from Sigma. 1,20(OH)2D3 and 20(OH)D3 were chemically synthesized. RNA SEQ: VDR-KO or scramble WM164 cells were plated onto 100 mm2 Petri dishes and treated with 1,25(OH)2D3, 25(OH)D3, 20(OH)D3, 1,20(OH)2D3 or ethanol (control) in triplicates. Cells were incubated in 10% charcoal-treated serum for 24 h. Cells were further harvested and RNA isolated using Absolutly RNA Miniprep Kit (Stratagen) . Approximately 120 ng/ul of each sample was sent for RNAseq analysis. BGI@CHOP genomics company sequenced the samples on Illumina HiSeq TM, analyzed, and sent us the results.
2024-06-01 | GSE248660 | GEO