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Review

Chimeric antigen receptor T-cell therapy for melanoma

, ORCID Icon, &
Pages 209-223 | Received 11 Nov 2020, Accepted 21 Jan 2021, Published online: 31 Jan 2021

References

  • Degenhardt Y, Huang J, Greshock J, et al. Distinct MHC gene expression patterns during progression of melanoma.. Genes Chromosomes Cancer. 2010 Feb;49(2):144–154.
  • Cichorek M, Wachulska M, Stasiewicz A, et al. Skin melanocytes: biology and development. Postepy Dermatol Alergol. 2013 Feb;30(1):30–41.
  • Ali Z, Yousaf N, Larkin J. Melanoma epidemiology, biology and prognosis. EJC Suppl. 2013 Sep;11(2):81–91.
  • Bandarchi B, Ma L, Navab R, et al. From melanocyte to metastatic malignant melanoma. Dermatol Res Pract. 2010;2010:583748.
  • Rabbie R, Ferguson P, Molina‐Aguilar C, et al. Melanoma subtypes: genomic profiles, prognostic molecular markers and therapeutic possibilities. J Pathol. 2019;247(5):539–551.
  • Rastrelli M, Tropea S, Rossi CR, et al. Melanoma: epidemiology, risk factors, pathogenesis, diagnosis and classification. In Vivo. 2014 Nov-Dec;28(6):1005–1011.
  • Khan AQ, Travers JB, Kemp MG. Roles of UVA radiation and DNA damage responses in melanoma pathogenesis. Environ Mol Mutagen. 2018;59(5):438–460.
  • Gerber B, Mathys P, Moser M, et al. Ultraviolet Emission Spectra of Sunbeds. Photochem Photobiol. 2002;76(6):664–668.
  • Bataille V, Boniol M, De Vries E, et al. A multicentre epidemiological study on sunbed use and cutaneous melanoma in Europe. Eur J Cancer. 2005;41(14):2141–2149.
  • Berwick M, Buller DB, Cust A, et al. Melanoma epidemiology and prevention. Melanoma: Springer; 2016. p. 17–49.
  • Kosary CL, Altekruse SF, Ruhl J, et al. Clinical and prognostic factors for melanoma of the skin using SEER registries: collaborative stage data collection system, version 1 and version 2. Cancer. 2014;120:3807–3814.
  • Nikolaou V, Stratigos A. Emerging trends in the epidemiology of melanoma. Br J Dermatol. 2014;170(1):11–19.
  • Coory M, Baade P, Aitken J, et al. Trends for in situ and invasive melanoma in Queensland, Australia, 1982–2002. Cancer Causes Control. 2006;17(1):21–27.
  • Marrett LD, Nguyen HL, Armstrong BK. Trends in the incidence of cutaneous malignant melanoma in New South Wales, 1983–1996. Int J Cancer. 2001;92(3):457–462.
  • Jemal A, Devesa SS, Hartge P, et al. Recent trends in cutaneous melanoma incidence among whites in the United States. JNCI Journal of the National Cancer Institute. 2001;93(9):678–683.
  • Jemal A, Saraiya M, Patel P, et al. Recent trends in cutaneous melanoma incidence and death rates in the United States, 1992–2006. J Am Acad Dermatol. 2011;65(5):S17. e1-S17. e11.
  • Ulmer MJ, Tonita JM, Hull PR. Trends in invasive cutaneous melanoma in Saskatchewan 1970–1999. Journal of Cutaneous Medicine and Surgery: Incorporating Medical and Surgical Dermatology. 2003;7(6):433–442.
  • MacKie RM, Bray CA, Hole DJ, et al. Incidence of and survival from malignant melanoma in Scotland: an epidemiological study. Lancet. 2002;360(9333):587–591.
  • Lasithiotakis KG, Leiter U, Gorkievicz R, et al. The incidence and mortality of cutaneous melanoma in Southern Germany: trends by anatomic site and pathologic characteristics, 1976 to 2003. Cancer. 2006;107(6):1331–1339.
  • Stang A, Pukkala E, Sankila R, et al. Time trend analysis of the skin melanoma incidence of Finland from 1953 through 2003 including 16,414 cases. Int J Cancer. 2006;119(2):380–384.
  • Lipsker D, Engel F, Cribier B, et al. Trends in melanoma epidemiology suggest three different types of melanoma. Br J Dermatol. 2007;157(2):338–343.
  • De Vries E, Bray FI, Coebergh JWW, et al. Changing epidemiology of malignant cutaneous melanoma in Europe 1953–1997: rising trends in incidence and mortality but recent stabilizations in western Europe and decreases in Scandinavia. Int J Cancer. 2003;107(1):119–126.
  • Shen W, Sakamoto N, Yang L. Melanoma-specific mortality and competing mortality in patients with non-metastatic malignant melanoma: a population-based analysis. BMC Cancer. 2016;16(1):413.
  • Matthews NH, Li W-Q, Qureshi AA, et al. Epidemiology of melanoma. Cutaneous melanoma: etiology and therapy [Internet]. Australia: Codon Publications; 2017.
  • Bhatia S, Tykodi SS, Thompson JA. Treatment of metastatic melanoma: an overview.. Oncology (Williston Park). 2009 May;23(6):488–496.
  • Tsao H, Olazagasti JM, Cordoro KM, et al. Early detection of melanoma: reviewing the ABCDEs. J Am Acad Dermatol. 2015 Apr;72(4):717–723.
  • Tarhini AA, Lee SJ, Hodi FS, et al. Phase III Study of Adjuvant Ipilimumab (3 or 10 mg/kg) Versus High-Dose Interferon Alfa-2b for Resected High-Risk Melanoma: north American Intergroup E1609. J Clin Oncol. 2020 Feb 20;38(6):567–575.
  • McKean MA, Amaria RN. Multidisciplinary treatment strategies in high-risk resectable melanoma: role of adjuvant and neoadjuvant therapy. Cancer Treat Rev. 2018;70:144–153.
  • Daneshvar F, Salehi F, Karimi M, et al. Combined X-ray radiotherapy and laser photothermal therapy of melanoma cancer cells using dual-sensitization of platinum nanoparticles. Journal of Photochemistry and Photobiology. B, Biology. 2020;203:111737.
  • Raigani S, Cohen S, Boland GM. The Role of Surgery for Melanoma in an Era of Effective Systemic Therapy. Curr Oncol Rep. 2017 Mar;19(3):17.
  • Si X, Gao Z, Xu F, et al. SOX2 upregulates side population cells and enhances their chemoresistant ability by transactivating ABCC1 expression contributing to intrinsic resistance to paclitaxel in melanoma. Mol Carcinog. 2019;59(3):257–264.
  • Joshi S, Durden DL. Combinatorial Approach to Improve Cancer Immunotherapy: rational Drug Design Strategy to Simultaneously Hit Multiple Targets to Kill Tumor Cells and to Activate the Immune System. J Oncol. 2019;2019:5245034.
  • Rosenberg SA, Restifo NPJS. Adoptive cell transfer as personalized immunotherapy for human cancer. Science (New York, N.Y.). 2015;348(6230):62–68.
  • Krug C, Birkholz K, Paulus A, et al. Stability and activity of MCSP-specific chimeric antigen receptors (CARs) depend on the scFv antigen-binding domain and the protein backbone. Cancer Immunology, Immunotherapy : CII. 2015;64(12):1623–1635.
  • Borrie AE, Vareki SM. T Lymphocyte–Based Cancer Immunotherapeutics. Int Rev Cell Mol Biol. 2018;341:201–276. Elsevier;
  • Scarfò I, Maus MV. Current approaches to increase CAR T cell potency in solid tumors: targeting the tumor microenvironment. J Immunother Cancer. 2017;5(1):28.
  • Ritchie DS, Neeson PJ, Khot A, et al. Persistence and efficacy of second generation CAR T cell against the LeY antigen in acute myeloid leukemia. Mol Ther. 2013;21(11):2122–2129.
  • Ugurel S, Rebmann V, Ferrone S, et al. Soluble human leukocyte antigen-G serum level is elevated in melanoma patients and is further increased by interferon-? immunotherapy. Cancer: Interdisciplinary International Journal of the American Cancer Society. 2001;92(2):369–376.
  • Kalaitsidou M, Kueberuwa G, Schütt A, et al. CAR T-cell therapy: toxicity and the relevance of preclinical models. Immunotherapy. 2015;7(5):487–497.
  • Tokarew N, Ogonek J, Endres S, et al. Teaching an old dog new tricks: next-generation CAR T cells. Br J Cancer. 2019;120(1):26–37.
  • Zhang J, Medeiros LJ, Young KH. Cancer Immunotherapy in Diffuse Large B-Cell Lymphoma. Front Oncol. 2018;8:351.
  • Stock S, Schmitt M, Sellner L. Optimizing Manufacturing Protocols of Chimeric Antigen Receptor T Cells for Improved Anticancer Immunotherapy. Int J Mol Sci. 2019 Dec 10;20(24):6223.
  • Akhavan D, Alizadeh D, Wang D, et al. CAR T cells for brain tumors: lessons learned and road ahead. Immunol Rev. 2019 Jul;290(1):60–84.
  • Wei J, Han X, Bo J, et al. Target selection for CAR-T therapy. J Hematol Oncol. 2019;12(1):62.
  • Zitelli JA, Brown CD, Hanusa BH. Surgical margins for excision of primary cutaneous melanoma. J Am Acad Dermatol. 1997;37(3):422–429.
  • Krementz ET, Ryan RF. Chemotherapy of melanoma of the extremities by perfusion: fourteen years clinical experience. Ann Surg. 1972;175(6):900.
  • Overgaard J. Radiation treatment of malignant melanoma. International Journal of Radiation Oncology*Biology*Physics. 1980;6(1):41–44.
  • Rosner S, Kwong E, Shoushtari AN, et al. Peripheral blood clinical laboratory variables associated with outcomes following combination nivolumab and ipilimumab immunotherapy in melanoma. Cancer Med. 2018;7(3):690–697.
  • Sweetlove M, Wrightson E, Kolekar S, et al. Inhibitors of pan-PI3K signaling synergize with BRAF or MEK inhibitors to prevent BRAF-mutant melanoma cell growth. Front Oncol. 2015;5:135.
  • Sabel MS, Arora A. The role of the surgeon in the management of melanoma. Minerva Chir. 2006 Apr;61(2):141–154.
  • Mohr P, Kiecker F, Soriano V, et al. Adjuvant therapy versus watch-and-wait post surgery for stage III melanoma: a multicountry retrospective chart review. Melanoma Manag. 2019 Oct 4;6(4):MMT33.
  • Young SE, Martinez SR, Essner R. The role of surgery in treatment of stage IV melanoma. Journal of Surgical Oncology. 2006;94(4):344–351.
  • Buzaid A, Colome M, Bedikian A, et al. Phase II study of neoadjuvant concurrent biochemotherapy in melanoma patients with local-regional metastases. Melanoma Res. 1998;8(6):549–556.
  • Bibault J-E, Dewas S, Mirabel X, et al. Adjuvant radiation therapy in metastatic lymph nodes from melanoma. Radiat Oncol. 2011;6(1):12.
  • Veronesi U, Adamus J, Aubert C, et al. A randomized trial of adjuvant chemotherapy and immunotherapy in cutaneous melanoma. N Engl J Med. 1982;307(15):913–916.
  • Fletcher WS, Pommier RF, Lum S, et al. Surgical treatment of metastatic melanoma. Am J Surg. 1998;175(5):413–417.
  • Eustace AJ, Crown J, Clynes M, et al. Preclinical evaluation of dasatinib, a potent Src kinase inhibitor, in melanoma cell lines. J Transl Med. 2008;6(1):53.
  • Silk AW, Kaufman HL, Curti B, et al. High-dose ipilimumab and high-dose interleukin-2 for patients with advanced melanoma. Frontiers in Oncology. 2020;9(1483): 10.3389/fonc.2019.01483
  • Megahed AI, Koon H. What is the role of chemotherapy in the treatment of melanoma? Current Treatment Options in Oncology. 2014;15(2):321–335.
  • Wilson MA, Schuchter LM. Chemotherapy for melanoma. In: Kaufman H, Mehnert J, editors. Melanoma. Vol. 167. Cham: Springer; 2016. p. 209–229.
  • McNeil EM, Astell KR, Ritchie A-M, et al. Inhibition of the ERCC1–XPF structure-specific endonuclease to overcome cancer chemoresistance. DNA Repair (Amst). 2015;31:19–28.
  • Lattanzi S, Tosteson T, Chertoff J, et al. Dacarbazine, cisplatin and carmustine, with or without tamoxifen, for metastatic melanoma: 5-year follow-up. Melanoma Res. 1995;5(5):365–369.
  • Legha SS, Ring S, Papadopoulos N, et al. A prospective evaluation of a triple‐drug regimen containing cisplatin, vinblastine, and dacarbazine (CVD) for metastatic melanoma. Cancer. 1989;64(10):2024–2029.
  • Agarwala S, Keilholz U, Hogg D, et al. Randomized phase III study of paclitaxel plus carboplatin with or without sorafenib as second-line treatment in patients with advanced melanoma. Journal of Clinical Oncology. 2007;25(18_suppl):8510.
  • Flaherty L, Hamid O, Linette G, et al. A single-arm, open-label, expanded access study of vemurafenib in patients with metastatic melanoma in the United States. Cancer J. 2014;20(1):18.
  • Legha S, Ring S, Bedikian A, et al. Treatment of metastatic melanoma with combined chemotherapy containing cisplatin, vinblastine and dacarbazine (CVD) and biotherapy using interleukin-2 and interferon-α. Ann Oncol. 1996;7(8):827–835.
  • Hauschild A, Garbe C, Stolz W, et al. Dacarbazine and interferon α with or without interleukin 2 in metastatic melanoma: a randomized phase III multicentre trial of the Dermatologic Cooperative Oncology Group (DeCOG). Br J Cancer. 2001;84(8):1036–1042.
  • Kaufmann R, Spieth K, Leiter U, et al. Temozolomide in combination with interferon-alfa versus temozolomide alone in patients with advanced metastatic melanoma: a randomized, phase III, multicenter study from the Dermatologic Cooperative Oncology Group. J clin oncol. 2005;23(35):9001–9007.
  • Tarhini AA, Kirkwood JM, Gooding WE, et al. Durable complete responses with high-dose bolus interleukin-2 in patients with metastatic melanoma who have experienced progression after biochemotherapy. J clin oncol. 2007;25(25):3802–3807.
  • Smith FO, Downey SG, Klapper JA, et al. Treatment of metastatic melanoma using interleukin-2 alone or in conjunction with vaccines. Clin Cancer Res. 2008;14(17):5610–5618.
  • Wolchok JD, Kluger H, Callahan MK, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369(2):122–133.
  • Long GV, Stroyakovskiy D, Gogas H, et al. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet. 2015;386(9992):444–451.
  • Falkson CI, Ibrahim J, Kirkwood JM, et al. Phase III trial of dacarbazine versus dacarbazine with interferon alpha-2b versus dacarbazine with tamoxifen versus dacarbazine with interferon alpha-2b and tamoxifen in patients with metastatic malignant melanoma: an Eastern Cooperative Oncology Group study. J clin oncol. 1998;16(5):1743–1751.
  • Rosenberg SA, Yang JC, Schwartzentruber DJ, et al. Prospective randomized trial of the treatment of patients with metastatic melanoma using chemotherapy with cisplatin, dacarbazine, and tamoxifen alone or in combination with interleukin-2 and interferon alfa-2b. J clin oncol. 1999;17(3):968.
  • Ridolfi R, Chiarion-Sileni V, Guida M, et al. Cisplatin, dacarbazine with or without subcutaneous interleukin-2, and interferon alfa-2b in advanced melanoma outpatients: results from an Italian multicenter phase III randomized clinical trial. J clin oncol. 2002;20(6):1600–1607.
  • Glover D, Glick JH, Weiler C, et al. WR-2721 and high-dose cisplatin: an active combination in the treatment of metastatic melanoma. J clin oncol. 1987;5(4):574–578.
  • Tanaka Y, Kitabatake K, Abe R, et al. Involvement of A2B Receptor in DNA Damage Response and Radiosensitizing Effect of A2B Receptor Antagonists on Mouse B16 Melanoma. Biol Pharm Bull. 2020 Mar 1;43(3):516–525.
  • Bonnen MD, Ballo MT, Myers JN, et al. Elective radiotherapy provides regional control for patients with cutaneous melanoma of the head and neck. Cancer. 2004;100(2):383–389.
  • Strojan PJR. oncology. Role of Radiotherapy in Melanoma Management. 2010;44(1):1–12.
  • Strojan P. Role of radiotherapy in melanoma management. Radiol Oncol. 2010 Mar;44(1):1–12.
  • Thariat J, Salleron J, Maschi C, et al. Oncologic and visual outcomes after postoperative proton therapy of localized conjunctival melanomas. Radiat Oncol. 2019 Dec 27;14(1):239.
  • D’Andrea MA, Reddy GKJROJ. Extracranial systemic antitumor response through the abscopal effect induced by brain radiation in a patient with metastatic melanoma. Radiation Oncology Journal. 2019;37(4):302.
  • Park S, Lee WJ, Park S, et al. Reversibly pH-responsive gold nanoparticles and their applications for photothermal cancer therapy. Sci Rep. 2019;9(1):1–9.
  • Seyedin SN, Schoenhals JE, Lee DA, et al. Strategies for combining immunotherapy with radiation for anticancer therapy. Immunotherapy. 2015;7(9):967–980.
  • Wernicke AG, Polce S, Parashar B. Role of Radiation in the Era of Effective Systemic Therapy for Melanoma. Surg Clin North Am. 2020 Feb;100(1):189–199.
  • Franklin C, Livingstone E, Roesch A, et al. Immunotherapy in melanoma: recent advances and future directions. Eur J Surg Oncol. 2017 Mar;43(3):604–611.
  • Maker AV, Phan GQ, Attia P, et al. Tumor regression and autoimmunity in patients treated with cytotoxic T lymphocyte–associated antigen 4 blockade and interleukin 2: a phase I/II study. Ann Surg Oncol. 2005;12(12):1005–1016.
  • Wing A, Fajardo CA, Posey AD, et al. Improving CART-cell therapy of solid tumors with oncolytic virus–driven production of a bispecific T-cell engager. Cancer Immunol Res. 2018;6(5):605–616.
  • Rochlitz C, Dreno B, Jantscheff P, et al. Immunotherapy of metastatic melanoma by intratumoral injections of Vero cells producing human IL-2: phase II randomized study comparing two dose levels. Cancer Gene Ther. 2002;9(3):289–295.
  • Ugurel S, Rebmann V, Ferrone S, et al. Soluble human leukocyte antigen–G serum level is elevated in melanoma patients and is further increased by interferon‐α immunotherapy. Cancer: Interdiscip Int J Am Cancer Soc. 2001;92(2):369–376.
  • Snyder A, Makarov V, Merghoub T, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014;371(23):2189–2199.
  • Madore J, Vilain RE, Menzies AM, et al. PD‐L1 expression in melanoma shows marked heterogeneity within and between patients: implications for anti‐PD‐1/PD‐L 1 clinical trials. Pigment Cell Melanoma Res. 2015;28(3):245–253.
  • Baghdadi M, Nagao H, Yoshiyama H, et al. Combined blockade of TIM-3 and TIM-4 augments cancer vaccine efficacy against established melanomas. Cancer Immunol Immunother. 2013;62(4):629–637.
  • Strome SE, Martin B, Flies D, et al. Enhanced therapeutic potential of adoptive immunotherapy by in vitro CD28/4-1BB costimulation of tumor-reactive T cells against a poorly immunogenic, major histocompatibility complex class I-negative A9P melanoma. J Immunother. 2000;23(4):430–437.
  • Fujiwara S, Nagai H, Shimoura N, et al. Intratumoral CD4+ T lymphodepletion sensitizes poorly immunogenic melanomas to immunotherapy with an OX40 agonist. J Invest Dermatol. 2014;134(7):1884–1892.
  • Holtzhausen A, Zhao F, Evans KS, et al. Melanoma-derived Wnt5a promotes local dendritic-cell expression of IDO and immunotolerance: opportunities for pharmacologic enhancement of immunotherapy. Cancer Immunol Res. 2015;3(9):1082–1095.
  • Naumova E, Mihaylova A, Stoitchkov K, et al. Genetic polymorphism of NK receptors and their ligands in melanoma patients: prevalence of inhibitory over activating signals. Cancer Immunol Immunother. 2005;54(2):172–178.
  • Wang JJ, Burger P, Taube J, et al. PD-L1, PD-1, LAG-3, and TIM-3 in Melanoma: expression in Brain Metastases Compared to Corresponding Extracranial Tumors. Cureus. 2019;11:12.
  • Buchbinder EI, Dutcher JP, Daniels GA, et al. Therapy with high-dose Interleukin-2 (HD IL-2) in metastatic melanoma and renal cell carcinoma following PD1 or PDL1 inhibition. J Immunother Cancer. 2019;7(1):49.
  • Wolkenstein P, Chosidow O, Wechsler J, et al. Cutaneous side effects associated with interleukin 2 administration for metastatic melanoma. J Am Acad Dermatol. 1993;28(1):66–70.
  • Curti B, Crittenden M, Seung SK, et al. Randomized phase II study of stereotactic body radiotherapy and interleukin-2 versus interleukin-2 in patients with metastatic melanoma. J Immunother Cancer. 2020;8:1.
  • Trinh VA, Zobniw C, Hwu W-J. The efficacy and safety of adjuvant interferon-alfa therapy in the evolving treatment landscape for resected high-risk melanoma. Expert Opin Drug Saf. 2017;16(8):933–940.
  • Mahoney KM, Freeman GJ, McDermott DF. The next immune-checkpoint inhibitors: PD-1/PD-L1 blockade in melanoma. Clin Ther. 2015;37(4):764–782.
  • Chikuma SCTLA. 4, an essential immune-checkpoint for T-cell activation. Emerging Concepts Targeting Immune Checkpoints in Cancer and Autoimmunity: Springer. 2017; 99–126.
  • Weber JS, O’Day S, Urba W, et al. Phase I/II study of ipilimumab for patients with metastatic melanoma. J Clin Oncol.  2008;26(36):5950–5956.
  • Camacho LH, Antonia S, Sosman J, et al. Phase I/II trial of tremelimumab in patients with metastatic melanoma. J Clin Oncol. 2009;27(7):1075–1081.
  • Callahan MK, Kluger H, Postow MA, et al. Nivolumab plus ipilimumab in patients with advanced melanoma: updated survival, response, and safety data in a phase I dose-escalation study. J Clin Oncol. 2018;36(4):391.
  • Banaszynski M, Kolesar J-S. Vemurafenib and ipilimumab: new agents for metastatic melanoma. Am J Health Syst Pharm. 2013;70(14):1205–1210.
  • 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):711–723.
  • Robert C, Ribas A, Wolchok JD, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet. 2014;384(9948):1109–1117. 2014/09/20/
  • Weber JS. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2015;16(4):375-384.
  • Rodríguez-Cerdeira C, Carnero Gregorio M, López-Barcenas A, et al. Advances in immunotherapy for melanoma: a comprehensive review. 2017;2017:3264217.
  • Gough MJ, Crittenden MR, Sarff M, et al. Adjuvant therapy with agonistic antibodies to CD134 (OX40) increases local control following surgical or radiation therapy of cancer in mice. J Immunother. 2010;33(8):798.
  • Peng W, Williams LJ, Xu C, et al. Anti-OX40 antibody directly enhances the function of tumor-reactive CD8+ T cells and synergizes with PI3Kβ inhibition in PTEN loss melanoma. Clin Cancer Res. 2019;25(21):6406–6416.
  • Kvarnhammar AM, Veitonmäki N, Hägerbrand K, et al. The CTLA-4 x OX40 bispecific antibody ATOR-1015 induces anti-tumor effects through tumor-directed immune activation. J Immunother Cancer. 2019;7(1):1–14.
  • Guo C, Manjili MH, Subjeck JR, et al. Therapeutic cancer vaccines: past, present, and future. Adv Cancer Res. 2013;119:421–475. Elsevier;
  • Schwartzentruber DJ, Lawson DH, Richards JM, et al. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma.. The New England Journal of Medicine. 2011;364(22):2119–2127.
  • Butterfield LH, Vujanovic L, Santos PM, et al. Multiple antigen-engineered DC vaccines with or without IFNα to promote antitumor immunity in melanoma. J Immunother Cancer. 2019;7(1):113.
  • Sheng L, Chen X, Wang Q, et al. Interferon-α2b enhances survival and modulates transcriptional profiles and the immune response in melanoma patients treated with dendritic cell vaccines.. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 2020;125(109966): 10.1016/j.biopha.2020.109966
  • Smith TT, Moffett HF, Stephan SB, et al. Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumors.. The Journal of Clinical Investigation. 2017;127(6):2176–2191.
  • Grenier JM, Yeung ST, Qiu Z, et al. Combining adoptive cell therapy with cytomegalovirus-based vaccine is protective against solid skin tumors. Front Immunol. 2018;8:1993.
  • Solari N, Spagnolo F, Ponte E, et al. Electrochemotherapy for the management of cutaneous and subcutaneous metastasis: a series of 39 patients treated with palliative intent. J Surg Oncol. 2014;109(3):270–274.
  • Atkins MB, Kunkel L, Sznol M, et al. High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update.. 2000;6 Suppl 1:S11–4. The Cancer Journal from Scientific American.
  • Richards J, Bedikian A, Gonzalez R, et al. High-dose Allovectin-7 in patients with advanced metastatic melanoma: final phase 2 data and design of phase 3 registration trial. J clin oncol. 2005;23(16_suppl):7543.
  • Sun J, Zager JS, Eroglu Z. Encorafenib/binimetinib for the treatment of BRAF-mutant advanced, unresectable, or metastatic melanoma: design, development, and potential place in therapy. Onco Targets Ther. 2018;11:9081.
  • Guo J, Carvajal R, Dummer R, et al. Efficacy and safety of nilotinib in patients with KIT-mutated metastatic or inoperable melanoma: final results from the global, single-arm, phase II TEAM trial. Ann Oncol. 2017;28(6):1380–1387.
  • 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):711–723.
  • Robert C, Long GV, Brady B, et al. Nivolumab in Previously Untreated Melanoma without BRAF Mutation. N Engl J Med. 2015;372(4):320–330.
  • Ott PA, Pavlick AC, Johnson DB, et al. A phase 2 study of glembatumumab vedotin, an antibody‐drug conjugate targeting glycoprotein NMB, in patients with advanced melanoma. Cancer. 2019;125(7):1113–1123.
  • Keilholz U, Mehnert JM, Bauer S, et al. Avelumab in patients with previously treated metastatic melanoma: phase 1b results from the JAVELIN Solid Tumor trial. J Immunother Cancer. 2019;7(1):12.
  • Yamazaki N, Takenouchi T, Fujimoto M, et al. Phase 1b study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced melanoma (KEYNOTE-041). Cancer Chemother Pharmacol. 2017;79(4):651–660.
  • Al-Sarraf M, Fletcher W, Oishi N, et al. Cisplatin hydration with and without mannitol diuresis in refractory disseminated malignant melanoma: a southwest oncology group study. Cancer Treat Rep. 1982;66(1):31–35.
  • Evans LM, Casper ES, Rosenbluth R. Phase I] trial of carboplatin in advanced malignant melanoma. Cancer Treat Rep. 1987;71(2):171–172.
  • Shah S, Luke JJ, Jacene HA, et al. Results from phase II trial of HSP90 inhibitor, STA-9090 (ganetespib), in metastatic uveal melanoma. Melanoma Res. 2018;28(6):605–610.
  • Olbryt M, Piglowski W, Rajczykowski M, et al. Genetic Profiling of Advanced Melanoma: candidate Mutations for Predicting Sensitivity and Resistance to Targeted Therapy. Target Oncol. 2020 Feb;15(1):101–113.
  • Croce L, Coperchini F, Magri F, et al. The multifaceted anti-cancer effects of BRAF-inhibitors. Oncotarget. 2019 Nov 12;10(61):6623–6640.
  • Flaherty KT, Robert C, Hersey P, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med. 2012;367(2):107–114.
  • Chapman PB, Hauschild A, Robert C, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364(26):2507–2516.
  • Poduje S, Brozic JM, Prkacin I, et al. Vemurafenib and cobimetinib-induced toxic epidermal necrolysis in a patient with metastatic melanoma. Dermatol Ther. 2020 Jan;33(1):e13174.
  • Koya RC, Mok S, Otte N, et al. BRAF inhibitor vemurafenib improves the antitumor activity of adoptive cell immunotherapy. Cancer Res. 2012;72(16):3928–3937.
  • Lo AS, Ma Q, Liu DL, et al. Anti-GD3 chimeric sFv-CD28/T-cell receptor zeta designer T cells for treatment of metastatic melanoma and other neuroectodermal tumors. Clin Cancer Res. 2010 May 15;16(10):2769–2780.
  • Perica K, Varela JC, Oelke M, et al. Adoptive T cell immunotherapy for cancer. Rambam Maimonides Med J. 2015 Jan;6(1):e0004.
  • Ellebaek E, Iversen TZ, Junker N, et al. Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients. J Transl Med. 2012;10(1):169.
  • Dudley ME, Wunderlich JR, Shelton TE, et al. Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients. J Immunother. 2003;26(4):332.
  • Poch M, Hall M, Joerger A, et al. Expansion of tumor infiltrating lymphocytes (TIL) from bladder cancer. Oncoimmunology. 2018;7(9):e1476816.
  • Duong CP, Yong CS, Kershaw MH, et al. Cancer immunotherapy utilizing gene-modified T cells: from the bench to the clinic. Mol Immunol. 2015 Oct;67(2 Pt A):46–57.
  • Shen X, Zhou J, Hathcock KS, et al. Persistence of tumor infiltrating lymphocytes in adoptive immunotherapy correlates with telomere length. J Immunother. 2007;30(1):123.
  • Duong CP, Yong CS, Kershaw MH, et al. Cancer immunotherapy utilizing gene-modified T cells: from the bench to the clinic. Mol Immunol. 2015;67(2):46–57.
  • Sun Q, Zhang X, Wang L, et al. T-cell receptor gene therapy targeting melanoma-associated antigen-A4 by silencing of endogenous TCR inhibits tumor growth in mice and human. Cell Death Dis. 2019 Jun 17;10(7):475.
  • He Q, Jiang X, Zhou X, et al. Targeting cancers through TCR-peptide/MHC interactions. J Hematol Oncol. 2019;12(1):1–17.
  • Merhavi-Shoham E, Itzhaki O, Markel G, et al. Adoptive Cell Therapy for Metastatic Melanoma. Cancer J. 2017 Jan/Feb;23(1):48–53.
  • Govers C, Sebestyen Z, Coccoris M, et al. T cell receptor gene therapy: strategies for optimizing transgenic TCR pairing. Trends Mol Med. 2010 Feb;16(2):77–87.
  • Rohaan MW, Wilgenhof S, Haanen J. Adoptive cellular therapies: the current landscape. Virchows Arch. 2019 Apr;474(4):449–461.
  • Zhang Q, Ping J, Huang Z, et al. CAR-T Cell Therapy in Cancer: Tribulations and Road Ahead 2020; 2020:
  • Goff SL, Morgan RA, Yang JC, et al. Pilot Trial of Adoptive Transfer of Chimeric Antigen Receptor–transduced T Cells Targeting EGFRvIII in Patients With Glioblastoma. J Immunother. 2019;42(4):126–135.
  • Xu J, Wang Q, Xu H, et al. Anti-BCMA CAR-T cells for treatment of plasma cell dyscrasia: case report on POEMS syndrome and multiple myeloma. J Hematol Oncol. 2018;11(1):1–9.
  • Haso W, Lee DW, Shah NN. et al. Anti-CD22–chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia. Blood, the Journal of the American Society of Hematology. 2013;121(7):1165–1174.
  • Hong H, Stastny M, Brown C, et al. Diverse solid tumors expressing a restricted epitope of L1-CAM can be targeted by chimeric antigen receptor redirected T lymphocytes. J Immunother. 2014;37(2):93–104.
  • Harrer DC, Schuler G, Dorrie J, et al. CSPG4-Specific CAR T Cells for High-Risk Childhood B Cell Precursor Leukemia. Int J Mol Sci. 2019 Jun 5;20(11):2764.
  • Geldres C, Savoldo B, Hoyos V, et al. T lymphocytes redirected against the chondroitin sulfate proteoglycan-4 control the growth of multiple solid tumors both in vitro and in vivo. Clinical Cancer Research : An Official Journal of the American Association for Cancer Research. 2014;20(4):962–971.
  • Harrer DC, Dörrie J, Schaft N. CSPG4 as Target for CAR-T-Cell Therapy of Various Tumor Entities–Merits and Challenges. Int J Mol Sci. 2019;20(23):5942.
  • Krishnamurthy J, Rabinovich BA, Mi T, et al. Genetic Engineering of T Cells to Target HERV-K, an Ancient Retrovirus on Melanoma. Clin Cancer Res. 2015 Jul 15;21(14):3241–3251.
  • Forsberg EM, Lindberg MF, Jespersen H, et al. HER2 CAR-T Cells Eradicate Uveal Melanoma and T-cell Therapy–Resistant Human Melanoma in IL2 Transgenic NOD/SCID IL2 Receptor Knockout Mice. Cancer Research. 2019;79(5):899–904.
  • Yu J, Wu X, Yan J, et al. Anti-GD2/4-1BB chimeric antigen receptor T cell therapy for the treatment of Chinese melanoma patients. J Hematol Oncol. 2018 Jan 3;11(1):1.
  • Kandil D, Leiman G, Allegretta M, et al. Glypican‐3 protein expression in primary and metastatic melanoma: a combined immunohistochemistry and immunocytochemistry study. Cancer Cytopathology: A Journal of the American Cancer Society. 2009;117(4):271–278.
  • Kan S, Konishi E, Arita T, et al. Podoplanin expression in cancer‐associated fibroblasts predicts aggressive behavior in melanoma. J Cutan Pathol. 2014;41(7):561–567.
  • Kageshita T, Funasaka Y, Ichihashi M, et al. Tissue factor expression and serum level in patients with melanoma does not correlate with disease progression. Pigment Cell Res. 2001;14(3):195–200.
  • Fisher J, Abramowski P, Don NDW, et al. Avoidance of on-target off-tumor activation using a co-stimulation-only chimeric antigen receptor. Mol Ther. 2017;25(5):1234–1247.
  • Theobald M. Current Immunotherapeutic Strategies in Cancer. Cham, Switzerland: Springer; 2020.
  • Akahori Y, Wang L, Yoneyama M, et al. Antitumor activity of CAR-T cells targeting the intracellular oncoprotein WT1 can be enhanced by vaccination.. Blood. 2018;132(11):1134–1145.
  • Srivastava S, Riddell SR. Chimeric Antigen Receptor T Cell Therapy: challenges to Bench-to-Bedside Efficacy. J Immunol. 2018 Jan 15;200(2):459–468.
  • Zhao Z, Chen Y, Francisco NM, et al. The application of CAR-T cell therapy in hematological malignancies: advantages and challenges. Acta Pharm Sin B. 2018 Jul;8(4):539–551.
  • Krug C, Birkholz K, Paulus A, et al. Stability and activity of MCSP-specific chimeric antigen receptors (CARs) depend on the scFv antigen-binding domain and the protein backbone. Cancer Immunol Immunother. 2015 Dec;64(12):1623–1635.
  • Chinnasamy D, Yu Z, Theoret MR, et al. Gene therapy using genetically modified lymphocytes targeting VEGFR-2 inhibits the growth of vascularized syngenic tumors in mice.. The Journal of Clinical Investigation. 2010;120(11):3953–3968.
  • Chinnasamy D, Tran E, Yu Z, et al. Simultaneous targeting of tumor antigens and the tumor vasculature using T lymphocyte transfer synergize to induce regression of established tumors in mice.. Cancer Research. 2013;73(11):3371–3380.
  • https://www.clinicaltrials.gov/ct2/show/NCT01218867. 2020 December, 20
  • Gargett T, Yu W, Dotti G, et al. GD2-specific CAR T Cells Undergo Potent Activation and Deletion Following Antigen Encounter but can be Protected From Activation-induced Cell Death by PD-1 Blockade.. Molecular Therapy : The Journal of the American Society of Gene Therapy. 2016;24(6):1135–1149.
  • https://www.clinicaltrials.gov/ct2/show/NCT02107963. December 20, 2020 [updated 2020 Dec 20].
  • https://www.clinicaltrials.gov/ct2/show/NCT02482532. December 20, 2020.
  • Shum T, Omer B, Tashiro H, et al. Constitutive Signaling from an Engineered IL7 Receptor Promotes Durable Tumor Elimination by Tumor-Redirected T Cells.. Cancer Discovery. 2017;7(11):1238–1247.
  • https://www.clinicaltrials.gov/ct2/show/NCT03635632. December 20, 2020.
  • Jin L, Ge H, Long Y, et al. CD70, a novel target of CAR T-cell therapy for gliomas.. Neuro-oncology. 2018;20(1):55–65.
  • Park YP, Jin L, Bennett KB, et al. CD70 as a target for chimeric antigen receptor T cells in head and neck squamous cell carcinoma.. Oral Oncology. 2018;78:145–150.
  • Yang M, Tang X, Zhang Z, et al. Tandem CAR-T cells targeting CD70 and B7-H3 exhibit potent preclinical activity against multiple solid tumors. 2020;10(17):7622.
  • https://www.clinicaltrials.gov/ct2/show/NCT02830724. December 20, 2020.
  • Gardner RA, Ceppi F, Rivers J, et al. Preemptive mitigation of CD19 CAR T-cell cytokine release syndrome without attenuation of antileukemic efficacy.. Blood. 2019;134(24):2149–2158.
  • https://www.clinicaltrials.gov/ct2/show/NCT04483778. December 20, 2020.
  • Lock D, Mockel-Tenbrinck N, Drechsel K, et al. Automated Manufacturing of Potent CD20-Directed Chimeric Antigen Receptor T Cells for Clinical Use.. Human Gene Therapy. 2017;28(10):914–925.
  • https://www.clinicaltrials.gov/ct2/show/NCT03893019. December 20, 2020.
  • Bianchi V, Bulek A, Fuller A, et al. A Molecular Switch Abrogates Glycoprotein 100 (gp100) T-cell Receptor (TCR) Targeting of a Human Melanoma Antigen.. The Journal of Biological Chemistry. 2016;291(17):8951–8959.
  • https://www.clinicaltrials.gov/ct2/show/NCT03649529. December 20, 2020
  • Raza A, Merhi M, Inchakalody VP, et al. Unleashing the immune response to NY-ESO-1 cancer testis antigen as a potential target for cancer immunotherapy. J Transl Med. 2020;18(1):140.
  • Maus MV, Plotkin J, Jakka G, et al. An MHC-restricted antibody-based chimeric antigen receptor requires TCR-like affinity to maintain antigen specificity.. Molecular Therapy Oncolytics. 2016;3(16023):1–9.
  • https://www.clinicaltrials.gov/ct2/show/NCT03638206. December 20, 2020.
  • https://www.clinicaltrials.gov/ct2/show/NCT04119024. December 20, 2020.
  • Hegde M, Mukherjee M, Grada Z, et al. Tandem CAR T cells targeting HER2 and IL13Rα2 mitigate tumor antigen escape.. The Journal of Clinical Investigation. 2016;126(8):3036–3052.
  • Kong S, Sengupta S, Tyler B, et al. Suppression of human glioma xenografts with second-generation IL13R-specific chimeric antigen receptor-modified T cells.. Clinical Cancer Research : An Official Journal of the American Association for Cancer Research. 2012;18(21):5949–5960.
  • Stock S, Schmitt M, Sellner L. Optimizing Manufacturing Protocols of Chimeric Antigen Receptor T Cells for Improved Anticancer Immunotherapy. Int J Mol Sci. 2019;20(24):6223.
  • Cherkassky L, Morello A, Villena-Vargas J, et al. Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition. J Clin Invest. 2016 Aug 1;126(8):3130–3144.
  • Maus MV, June CH. Making better chimeric antigen receptors for adoptive T-cell therapy. AACR. 2016;22(8):1875–1884.
  • Rafiq S, Yeku OO, Jackson HJ, et al. Targeted delivery of a PD-1-blocking scFv by CAR-T cells enhances anti-tumor efficacy in vivo. Nat Biotechnol. 2018 Oct;36(9):847–856.
  • Hoogi S, Eisenberg V, Mayer S, et al. A TIGIT-based chimeric co-stimulatory switch receptor improves T-cell anti-tumor function. Journal for Immunotherapy of Cancer. 2019;7(1):243.
  • Mahnke K, Enk A. TIGIT-CD155 interactions in melanoma: a novel co-inhibitory pathway with potential for clinical intervention. The Journal of Investigative Dermatology. 2016;136(1):9–11.
  • Wiesinger M, März J, Kummer M, et al. Clinical-Scale Production of CAR-T Cells for the Treatment of Melanoma Patients by mRNA Transfection of a CSPG4-Specific CAR under Full GMP Compliance. Cancers. 2019;11(8):1198.
  • Bommhardt U, Schraven B, Simeoni L. Beyond TCR signaling: emerging functions of Lck in cancer and immunotherapy. International Journal of Molecular Sciences. 2019;20(14):3500.
  • Perna SK, Pagliara D, Mahendravada A, et al. Interleukin-7 mediates selective expansion of tumor-redirected cytotoxic T lymphocytes (CTLs) without enhancement of regulatory T-cell inhibition. Clin Cancer Res. 2014;20(1):131–139.

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