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Current Pharmaceutical Design

Author(s): Hardeep Singh Tuli*, Katrin Sak, Ashif Iqubal, Renuka Choudhary, Shubham Adhikary, Ginpreet Kaur, Pawan Kumar and Vivek Kumar Garg

DOI: 10.2174/1381612828666220727124639

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Recent Advances in Immunotherapy for the Treatment of Malignant Melanoma

Page: [2363 - 2374] Pages: 12

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Abstract

Malignant melanoma is one of the most worrisome malignancies due to its fast dissemination and early formation of metastases in multiple sites throughout the body. Despite the intensive efforts made in the last decades, the use of standard therapeutic strategies, including chemotherapy and radiotherapy, has not led to a substantial improvement in clinical outcomes, mainly because of the intrinsic resistance of melanomas to these treatment modalities. Therefore, in recent years, numerous studies have focused on the possibility of boosting the clinical responses of melanoma patients by using novel immunotherapeutic agents. In this review article, a comprehensive survey is presented about the approved immunotherapeutic drugs and their action mechanisms, besides describing the agents that are currently still in clinical trials. Moreover, the combination of immunotherapeutic drugs with conventional approaches, i.e., radiotherapy, chemotherapy, and targeted therapy, is another focal point of this review, providing valuable input for further elaboration of the best treatment regimens to prolong survival and improve the quality of life of melanoma patients.

Keywords: Melanoma, immunotherapy, clinical trials, radiotherapy, chemotherapy, treatment regimens.

[1]
Wyld L, Audisio RA, Poston GJ. The evolution of cancer surgery and future perspectives. Nat Rev Clin Oncol 2015; 12(2): 115-24.
[http://dx.doi.org/10.1038/nrclinonc.2014.191] [PMID: 25384943]
[2]
Baskar R, Lee KA, Yeo R, Yeoh KW. Cancer and radiation therapy: Current advances and future directions. Int J Med Sci 2012; 9(3): 193-9.
[http://dx.doi.org/10.7150/ijms.3635] [PMID: 22408567]
[3]
Chabner BA, Roberts TG Jr. Timeline: Chemotherapy and the war on cancer. Nat Rev Cancer 2005; 5(1): 65-72.
[http://dx.doi.org/10.1038/nrc1529] [PMID: 15630416]
[4]
Valladares BT, Crespo PC, Herranz UA, Caamaño AG. Adjuvant treatment in lung cancer. J Clin Transl Res 2021; 7(2): 175-84.
[PMID: 34104820]
[5]
Román-Jobacho A, Hernández-Miguel M, García-Anaya MJ, Gómez-Millán J, Medina-Carmona JAO-RA, Otero-Romero A. Oligometastatic non-small cell lung cancer: Current management. J Clin Transl Res 2021; 7(3): 311-9.
[PMID: 34239990]
[6]
Srivani G, Peela S, Afroz A. Gemcitabine for pancreatic cancer. Cancer Plus 2021; S1: 20-32.
[7]
Pedersen B, Koktved DP, Nielsen LL. Living with side effects from cancer treatment-a challenge to target information. Scand J Caring Sci 2013; 27(3): 715-23.
[http://dx.doi.org/10.1111/j.1471-6712.2012.01085.x] [PMID: 23034150]
[8]
Arruebo M, Vilaboa N, Sáez-Gutierrez B, et al. Assessment of the evolution of cancer treatment therapies. Cancers 2011; 3(3): 3279-330.
[http://dx.doi.org/10.3390/cancers3033279] [PMID: 24212956]
[9]
Zhang H, Chen J. Current status and future directions of cancer immunotherapy. J Cancer 2018; 9(10): 1773-81.
[PMID: 29805703]
[10]
Yang Z, Xu Y, Bi Y, et al. Immune escape mechanisms and immunotherapy of urothelial bladder cancer. J Clin Transl Res 2021; 7(4): 485.
[11]
Lu X, Shi H, Que Q, Qiu S. Research progress in immunotherapy of advanced non-small cell lung cancer. Trends Immunother 2021; 5(21): 58-64.
[http://dx.doi.org/10.24294/ti.v5.i2.1.1367]
[12]
Xie R. Combining PD-1/PD-l1 inhibitor and parp inhibitor: A new perspective on the treatment of triple negative breast cancer. Trends Immunother 2021; 5(2.1): 24-9.
[13]
Furukawa F. Effects of immune checkpoint inhibitors on cancer patients with preexisting autoimmune disease. Trends Immunother 2021; 5(1): 5-6.
[14]
Liu M, Guo F. Recent updates on cancer immunotherapy. Precis Clin Med 2018; 1(2): 65-74.
[PMID: 30687562]
[15]
Inthagard J, Edwards J, Roseweir AK. Immunotherapy: Enhancing the efficacy of this promising therapeutic in multiple cancers. Clin Sci 2019; 133(2): 181-93.
[PMID: 30659159]
[16]
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71(3): 209-49.
[PMID: 33538338]
[17]
Bray F, Ferlay J, Isabelle Soerjomataram RLS, Torre LA, Jemal A. Erratum: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2020; 70(4): 313-.
[http://dx.doi.org/10.3322/caac.21609] [PMID: 32767693]
[18]
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55(2): 74-108.
[PMID: 15761078]
[19]
Leonardi GC, Falzone L, Salemi R, et al. Cutaneous melanoma: From pathogenesis to therapy (Review). Int J Oncol 2018; 52(4): 1071-80.
[PMID: 29532857]
[20]
Macdonald EJ. Epidemiology of melanoma. Prog Clin Cancer 1975; 6: 139-49.
[PMID: 1197753]
[21]
Ali Z, Yousaf N, Larkin J. Melanoma epidemiology, biology and prognosis. Eur J Cancer 2013; 11(2): 81-91.
[PMID: 26217116]
[22]
Yang K, Fung TT, Nan H. An epidemiological review of diet and cutaneous malignant melanoma. Cancer Epidemiol Biomarkers Prev 2018; 27(10): 1115-22.
[http://dx.doi.org/10.1158/1055-9965.EPI-18-0243] [PMID: 30018150]
[23]
Rossi M, Pellegrini C, Cardelli L, Ciciarelli V, Di Nardo L, Fargnoli MC. Familial melanoma: Diagnostic and management implications. Dermatol Pract Concept 2019; 9(1): 10-6.
[http://dx.doi.org/10.5826/dpc.0901a03] [PMID: 30775140]
[24]
Naik PP. Current trends of immunotherapy in the treatment of cutaneous melanoma: A Review. Dermatol Ther 2021; 11(5): 1481-96.
[http://dx.doi.org/10.1007/s13555-021-00583-z]
[25]
Allen T, Gundrajakuppam L. A role of immunotherapy in metastatic malignant melanoma. Cent Nerv Syst Agents Med Chem 2012; 12(3): 182-8.
[http://dx.doi.org/10.2174/187152412802430165] [PMID: 22697295]
[26]
Bomar L, Senithilnathan A, Ahn C. Systemic therapies for advanced melanoma. Dermatol Clin 2019; 37(4): 409-23.
[http://dx.doi.org/10.1016/j.det.2019.05.001] [PMID: 31466582]
[27]
Ralli M, Botticelli A, Irene Claudia V, et al. Immunotherapy in the treatment of metastatic melanoma: Current knowledge and future directions. J Immunol Res 2020; 2020: 9235638.
[28]
Haanen JBAG. Immunotherapy of melanoma. Eur J Cancer 2013; 11(2): 97-105.
[http://dx.doi.org/10.1016/j.ejcsup.2013.07.013] [PMID: 26217118]
[29]
Melief CJM, van Hall T, Arens R, Ossendorp F, van der Burg SH. Therapeutic cancer vaccines. J Clin Invest 2015; 125(9): 3401-12.
[http://dx.doi.org/10.1172/JCI80009] [PMID: 26214521]
[30]
Coventry BJ. Therapeutic vaccination immunomodulation: Forming the basis of all cancer immunotherapy. Ther Adv Vaccines Immunother 2019; 7: 2515135519862234.
[http://dx.doi.org/10.1177/2515135519862234] [PMID: 31414074]
[31]
Kimpel J, Urbiola C, Koske I, et al. The oncolytic virus VSV-GP is effective against malignant melanoma. Viruses 2018; 10(3): E108.
[http://dx.doi.org/10.3390/v10030108] [PMID: 29498639]
[32]
Pol J, Kroemer G, Galluzzi L. First oncolytic virus approved for melanoma immunotherapy. OncoImmunology 2015; 5(1): e1115641.
[http://dx.doi.org/10.1080/2162402X.2015.1115641] [PMID: 26942095]
[33]
Andtbacka RHI, Kaufman HL, Collichio F, et al. Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J Clin Oncol 2015; 33(25): 2780-8.
[http://dx.doi.org/10.1200/JCO.2014.58.3377] [PMID: 26014293]
[34]
Puzanov I, Milhem MM, Minor D, et al. Talimogene laherparepvec in combination with ipilimumab in previously untreated, unresectable stage IIIB-IV melanoma. J Clin Oncol 2016; 34(22): 2619-26.
[http://dx.doi.org/10.1200/JCO.2016.67.1529] [PMID: 27298410]
[35]
Liu BL, Robinson M, Han ZQ, et al. ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties. Gene Ther 2003; 10(4): 292-303.
[http://dx.doi.org/10.1038/sj.gt.3301885] [PMID: 12595888]
[36]
Huber A, Dammeijer F, Aerts JGJV, Vroman H. Current state of dendritic cell-based immunotherapy: Opportunities for in vitro antigen loading of different DC subsets? Front Immunol 2018; 9: 2804.
[http://dx.doi.org/10.3389/fimmu.2018.02804] [PMID: 30559743]
[37]
Merhavi-Shoham E, Itzhaki O, Markel G, Schachter J, Besser MJ. Adoptive cell therapy for metastatic melanoma. Cancer J 2017; 23(1): 48-53.
[http://dx.doi.org/10.1097/PPO.0000000000000240] [PMID: 28114254]
[38]
Brunet JF, Denizot F, Luciani MF, et al. A new member of the immunoglobulin superfamily-CTLA-4. Nature 1987; 328(6127): 267-70.
[http://dx.doi.org/10.1038/328267a0] [PMID: 3496540]
[39]
Bhandaru M, Rotte A. Monoclonal antibodies for the treatment of melanoma: Present and future strategies.In: Methods Mol Biol. 2019; 1904: pp. 83-108.
[http://dx.doi.org/10.1007/978-1-4939-8958-4_4] [PMID: 30539467]
[40]
Peggs KS, Quezada SA, Korman AJ, Allison JP. Principles and use of anti-CTLA4 antibody in human cancer immunotherapy. Curr Opin Immunol 2006; 18(2): 206-13.
[http://dx.doi.org/10.1016/j.coi.2006.01.011] [PMID: 16464564]
[41]
Syn NL, Teng MWL, Mok TSK, Soo RA. De-novo and acquired resistance to immune checkpoint targeting. Lancet Oncol 2017; 18(12): e731-41.
[http://dx.doi.org/10.1016/S1470-2045(17)30607-1] [PMID: 29208439]
[42]
Achkar T, Tarhini AA. The use of immunotherapy in the treatment of melanoma. J Hematol Oncol 2017; 10: 88.
[43]
Robert C, Ghiringhelli F. What is the role of cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma? Oncologist 2009; 14(8): 848-61.
[http://dx.doi.org/10.1634/theoncologist.2009-0028] [PMID: 19648604]
[44]
Chen L. Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat Rev Immunol 2004; 4(5): 336-47.
[http://dx.doi.org/10.1038/nri1349] [PMID: 15122199]
[45]
Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 2000; 192(7): 1027-34.
[http://dx.doi.org/10.1084/jem.192.7.1027] [PMID: 11015443]
[46]
Gajewski TF. Identifying and overcoming immune resistance mechanisms in the melanoma tumor microenvironment. Clin Cancer Res 2006; 12: 2326s-30s.
[47]
Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci USA 2002; 99(19): 12293-7.
[http://dx.doi.org/10.1073/pnas.192461099] [PMID: 12218188]
[48]
Latchman Y, Wood CR, Chernova T, et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol 2001; 2(3): 261-8.
[http://dx.doi.org/10.1038/85330] [PMID: 11224527]
[49]
Ghosh C, Luong G, Sun Y. A snapshot of the PD-1/PD-L1 pathway. J Cancer 2021; 12(9): 2735-46.
[http://dx.doi.org/10.7150/jca.57334] [PMID: 33854633]
[50]
Raedler LA. Keytruda (Pembrolizumab): First PD-1 inhibitor approved for previously treated unresectable or metastatic melanoma. Am Heal drug benefits 2015; 8: 96-100.
[51]
Kirkwood JM, Ernstoff MS, Davis CA, Reiss M, Ferraresi R, Rudnick SA. Comparison of intramuscular and intravenous recombinant alpha-2 interferon in melanoma and other cancers. Ann Intern Med 1985; 103(1): 32-6.
[http://dx.doi.org/10.7326/0003-4819-103-1-32] [PMID: 4003987]
[52]
Rosenberg SA, Packard BS, Aebersold PM, et al. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N Engl J Med 1988; 319(25): 1676-80.
[http://dx.doi.org/10.1056/NEJM198812223192527] [PMID: 3264384]
[53]
Minasian LM, Szatrowski TP, Rosenblum M, et al. Hemorrhagic tumor necrosis during a pilot trial of tumor necrosis factor-α and anti-GD3 ganglioside monoclonal antibody in patients with metastatic melanoma. Blood 1994; 83(1): 56-64.
[http://dx.doi.org/10.1182/blood.V83.1.56.56] [PMID: 8274754]
[54]
Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: The eastern cooperative oncology group trial EST 1684. J Clin Oncol 1996; 14(1): 7-17.
[http://dx.doi.org/10.1200/JCO.1996.14.1.7] [PMID: 8558223]
[55]
Fong L, Small EJ. Anti-cytotoxic T-lymphocyte antigen-4 antibody: The first in an emerging class of immunomodulatory antibodies for cancer treatment. J Clin Oncol 2008; 26(32): 5275-83.
[http://dx.doi.org/10.1200/JCO.2008.17.8954] [PMID: 18838703]
[56]
Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363(8): 711-23.
[http://dx.doi.org/10.1056/NEJMoa1003466] [PMID: 20525992]
[57]
Ng Tang D, Shen Y, Sun J, et al. Increased frequency of ICOS+ CD4 T cells as a pharmacodynamic biomarker for anti-CTLA-4 therapy. Cancer Immunol Res 2013; 1(4): 229-34.
[http://dx.doi.org/10.1158/2326-6066.CIR-13-0020] [PMID: 24777852]
[58]
Wróbel S, Przybyło M, Stępień E. The clinical trial landscape for melanoma therapies. J Clin Med 2019; 8(3): 368.
[http://dx.doi.org/10.3390/jcm8030368] [PMID: 30884760]
[59]
Wu S, Singh RK. Resistance to chemotherapy and molecularly targeted therapies: Rationale for combination therapy in malignant melanoma. Curr Mol Med 2011; 11(7): 553-63.
[http://dx.doi.org/10.2174/156652411800615153] [PMID: 21707515]
[60]
Turcotte S, Rosenberg SA. Immunotherapy for metastatic solid cancers. Adv Surg 2011; 45(1): 341-60.
[http://dx.doi.org/10.1016/j.yasu.2011.04.003] [PMID: 21954698]
[61]
Smalley KSM, Eroglu Z, Sondak VK. Combination therapies for melanoma: A new standard of care? Am J Clin Dermatol 2016; 17(2): 99-105.
[http://dx.doi.org/10.1007/s40257-016-0174-8] [PMID: 26860106]
[62]
Wang S, Zhao Z, Barber B, Wagner VJ. Surgery, radiation, and systemic therapies in patients with metastatic melanoma. J Clin Oncol 2012; 30(15): e19044-4.
[http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e19044]
[63]
Davis LE, Shalin SC, Tackett AJ. Current state of melanoma diagnosis and treatment. Cancer Biol Ther 2019; 20(11): 1366-79.
[http://dx.doi.org/10.1080/15384047.2019.1640032] [PMID: 31366280]
[64]
Tagliaferri L, Lancellotta V, Fionda B, et al. Immunotherapy and radiotherapy in melanoma: A multidisciplinary comprehensive review. Hum Vaccin Immunother 2022; 18(3): 1903827.
[65]
Jiang W, Chan CK, Weissman IL, Kim BYS, Hahn SM. Immune priming of the tumor microenvironment by radiation. Trends Cancer 2016; 2(11): 638-45.
[http://dx.doi.org/10.1016/j.trecan.2016.09.007] [PMID: 28741502]
[66]
Kiess AP, Wolchok JD, Barker CA, et al. Stereotactic radiosurgery for melanoma brain metastases in patients receiving ipilimumab: Safety profile and efficacy of combined treatment. Int J Radiat Oncol Biol Phys 2015; 92(2): 368-75.
[http://dx.doi.org/10.1016/j.ijrobp.2015.01.004] [PMID: 25754629]
[67]
Silk AW, Bassetti MF, West BT, Tsien CI, Lao CD. Ipilimumab and radiation therapy for melanoma brain metastases. Cancer Med 2013; 2(6): 899-906.
[http://dx.doi.org/10.1002/cam4.140] [PMID: 24403263]
[68]
Liniker E, Menzies AM, Kong BY, et al. Activity and safety of radiotherapy with anti-PD-1 drug therapy in patients with metastatic melanoma. OncoImmunology 2016; 5(9): e1214788.
[http://dx.doi.org/10.1080/2162402X.2016.1214788] [PMID: 27757312]
[69]
Yan Y, Kumar A, Finnes H, Markovic S, Park S. Combining immune checkpoint inhibitors with conventional cancer therapy. Front Immunol 2018; 9: 1739.
[70]
Alizadeh D, Larmonier N. Chemotherapeutic targeting of cancer-induced immunosuppressive cells. Cancer Res 2014; 74(10): 2663-8.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-0301] [PMID: 24778417]
[71]
Ghiringhelli F, Menard C, Puig PE, et al. Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother 2007; 56(5): 641-8.
[http://dx.doi.org/10.1007/s00262-006-0225-8] [PMID: 16960692]
[72]
Vera Aguilera J, Paludo J, McWilliams RR, et al. Chemo-immunotherapy combination after PD-1 inhibitor failure improves clinical outcomes in metastatic melanoma patients. Melanoma Res 2020; 30(4): 364-75.
[http://dx.doi.org/10.1097/CMR.0000000000000669] [PMID: 32404734]
[73]
Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 2011; 364(26): 2517-26.
[http://dx.doi.org/10.1056/NEJMoa1104621] [PMID: 21639810]
[74]
Di Giacomo AM, Ascierto PA, Pilla L, et al. Ipilimumab and fotemustine in patients with advanced melanoma (NIBIT-M1): An open-label, single-arm phase 2 trial. Lancet Oncol 2012; 13(9): 879-86.
[http://dx.doi.org/10.1016/S1470-2045(12)70324-8] [PMID: 22894884]
[75]
Coffelt SB, de Visser KE. Immune-mediated mechanisms influencing the efficacy of anticancer therapies. Trends Immunol 2015; 36(4): 198-216.
[http://dx.doi.org/10.1016/j.it.2015.02.006] [PMID: 25857662]
[76]
Liu L, Mayes PA, Eastman S, et al. The BRAF and MEK inhibitors dabrafenib and trametinib: Effects on immune function and in combination with immunomodulatory antibodies targeting PD-1, PD-L1, and CTLA-4. Clin Cancer Res 2015; 21(7): 1639-51.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-2339] [PMID: 25589619]
[77]
Hu-Lieskovan S, Mok S, Homet Moreno B, et al. Improved antitumor activity of immunotherapy with BRAF and MEK inhibitors in BRAF(V600E) melanoma. Sci Transl Med 2015; 7(279): 279ra41.
[http://dx.doi.org/10.1126/scitranslmed.aaa4691] [PMID: 25787767]
[78]
Homet Moreno B, Mok S, Comin-Anduix B, Hu-Lieskovan S, Ribas A. Combined treatment with dabrafenib and trametinib with immune-stimulating antibodies for BRAF mutant melanoma. OncoImmunology 2015; 5(7): e1052212.
[http://dx.doi.org/10.1080/2162402X.2015.1052212] [PMID: 27622011]
[79]
Ebert PJR, Cheung J, Yang Y, et al. MAP kinase inhibition promotes T cell and anti-tumor activity in combination with PD-L1 checkpoint blockade. Immunity 2016; 44(3): 609-21.
[http://dx.doi.org/10.1016/j.immuni.2016.01.024] [PMID: 26944201]
[80]
Knight DA, Ngiow SF, Li M, et al. Host immunity contributes to the anti-melanoma activity of BRAF inhibitors. J Clin Invest 2013; 123(3): 1371-81.
[http://dx.doi.org/10.1172/JCI66236] [PMID: 23454771]
[81]
Deken MA, Gadiot J, Jordanova ES, et al. Targeting the MAPK and PI3K pathways in combination with PD1 blockade in melanoma. OncoImmunology 2016; 5(12): e1238557.
[http://dx.doi.org/10.1080/2162402X.2016.1238557] [PMID: 28123875]
[82]
Amin A, Lawson DH, Salama AKS, et al. Phase II study of vemurafenib followed by ipilimumab in patients with previously untreated BRAF-mutated metastatic melanoma. J Immunother Cancer 2016; 4(1): 44.
[http://dx.doi.org/10.1186/s40425-016-0148-7] [PMID: 27532019]
[83]
Ribas A, Butler M, Lutzky J, et al. Phase I study combining anti-PD-L1 (MEDI4736) with BRAF (dabrafenib) and/or MEK (trametinib) inhibitors in advanced melanoma. J Clin Oncol 2015; 33(15): 3003-.
[http://dx.doi.org/10.1200/jco.2015.33.15_suppl.3003]