Combining locoregional CAR-T cells, autologous + allogeneic tumor lysate vaccination and levamisole in treatment of glioblastoma

References

• Chuntova P, Downey KM, Hegde B, et al. Genetically engineered T-cells for malignant glioma: overcoming the barriers to effective immunotherapy. Front Immunol. 2018;9:3062.
   PubMed Web of Science ®Google Scholar
• Choi BD, Maus MV, June CH, et al. Immunotherapy for glioblastoma: adoptive T-cell strategies. Clin Cancer Res. 2019;25(7):2042–2048.
   PubMed Web of Science ®Google Scholar
• Grimm SA, Chamberlain MC. State of the art and perspectives in the treatment of glioblastoma. CNS Oncol. 2012;1(1):49–70.
   PubMedGoogle Scholar
• Chamberlain MC. Temozolomide: therapeutic limitations in the treatment of adult high-grade gliomas. Expert Rev Neurother. 2010;10(10):1537–1544.
   PubMed Web of Science ®Google Scholar
• Choi S, Yu Y, Grimmer MR, et al. Temozolomide-associated hypermutation in gliomas. Neuro Oncol. 2018;20(10):1300–1309.
   PubMed Web of Science ®Google Scholar
• Bambury RM, Morris PG. The search for novel therapeutic strategies in the treatment of recurrent glioblastoma multiforme. Expert Rev Anticancer Ther. 2014;14(8):955–964.
   PubMed Web of Science ®Google Scholar
• Kaka N, Hafazalla K, Samawi H, et al. Progression-free but no overall survival benefit for adult patients with bevacizumab therapy for the treatment of newly diagnosed glioblastoma: a systematic review and meta-analysis. Cancers. 2019;11(11):1723.
   PubMed Web of Science ®Google Scholar
• Mooney J, Bernstock JD, Ilyas A, et al. Current approaches and challenges in the molecular therapeutic targeting of glioblastoma. World Neurosurg. 2019;129:90–100.
   PubMed Web of Science ®Google Scholar
• O'Rourke DM, Nasrallah MP, Desai A, et al. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med. 2017;9(399):eaaa0984.
   PubMed Web of Science ®Google Scholar
• Ahmed N, Brawley V, Hegde M, et al. HER2-specific chimeric antigen receptor-modified virus-specific T cells for progressive glioblastoma: a phase 1 dose-escalation trial. JAMA Oncol. 2017;3(8):1094–1101.
   PubMed Web of Science ®Google Scholar
• Brown CE, Badie B, Barish ME, et al. Bioactivity and safety of IL13Rα2-redirected chimeric antigen receptor CD8+ T cells in patients with recurrent glioblastoma. Clin Cancer Res. 2015;21(18):4062–4072.
   PubMed Web of Science ®Google Scholar
• Brown CE, Alizadeh D, Starr R, et al. Regression of glioblastoma after chimeric antigen receptor T-cell therapy. N Engl J Med. 2016;375(26):2561–2569.
   PubMed Web of Science ®Google Scholar
• Mangani D, Weller M, Roth P. The network of immunosuppressive pathways in glioblastoma. Biochem Pharmacol. 2017;130:1–9.
   PubMed Web of Science ®Google Scholar
• Krenciute G, Prinzing BL, Yi Z, et al. Transgenic expression of IL15 improves antiglioma activity of IL13Rα2-CAR T cells but results in antigen loss variants. Cancer Immunol Res. 2017;5(7):571–581.
   PubMed Web of Science ®Google Scholar
• Zhu X, Fallert-Junecko BA, Fujita M, et al. Poly-ICLC promotes the infiltration of effector T cells into intracranial gliomas via induction of CXCL10 in IFN-alpha and IFN-gamma dependent manners. Cancer Immunol Immunother. 2010;59(9):1401–1409.
   PubMed Web of Science ®Google Scholar
• Guo H, Zhang T, Yu Y, et al. Cancer physical hallmarks as new targets for improved immunotherapy. Trends Cell Biol. 2021;31(7):520–524.
   PubMed Web of Science ®Google Scholar
• Chheda ZS, Kohanbash G, Okada K, et al. Novel and shared neoantigen derived from histone 3 variant H3.3K27M mutation for glioma T cell therapy. J Exp Med. 2018;215(1):141–157.
   PubMed Web of Science ®Google Scholar
• Globerson-Levin A, Waks T, Eshhar Z. Elimination of progressive mammary cancer by repeated administrations of chimeric antigen receptor-modified T cells. Mol Ther. 2014;22(5):1029–1038.1038/mt.2014.28
   PubMed Web of Science ®Google Scholar
• Adusumilli PS, Cherkassky L, Villena-Vargas J, et al. Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity. Sci Transl Med. 2014;6(261):261ra151.
   PubMed Web of Science ®Google Scholar
• Katz SC, Point GR, Cunetta M, et al. Regional CAR-T cell infusions for peritoneal carcinomatosis are superior to systemic delivery. Cancer Gene Ther. 2016;23(5):142–148.
   PubMed Web of Science ®Google Scholar
• Sridhar P, Petrocca F. Regional delivery of chimeric antigen receptor (CAR) T-cells for cancer therapy. Cancers. 2017;9(7):92.
   PubMed Web of Science ®Google Scholar
• Priceman SJ, Tilakawardane D, Jeang B, et al. Regional delivery of chimeric antigen receptor-engineered T cells effectively targets HER2+ breast cancer metastasis to the brain. Clin Cancer Res. 2018;24(1):95–105.
   PubMed Web of Science ®Google Scholar
• Tchou J, Zhao Y, Levine BL, et al. Safety and efficacy of intratumoral injections of chimeric antigen receptor (CAR) T cells in metastatic breast cancer. Cancer Immunol Res. 2017;5(12):1152–1161.
   PubMed Web of Science ®Google Scholar
• Atik AF, Suryadevara CM, Schweller RM, et al. Hyaluronic acid based low viscosity hydrogel as a novel carrier for convection enhanced delivery of CAR T cells. J Clin Neurosci. 2018;56:163–168.
   PubMed Web of Science ®Google Scholar
• Mount CW, Majzner RG, Sundaresh S, et al. Potent antitumor efficacy of anti-GD2 CAR T cells in H3-K27M + diffuse midline gliomas. Nat Med. 2018;24(5):572–579.
   PubMed Web of Science ®Google Scholar
• Richman SA, Nunez-Cruz S, Moghimi B, et al. High-affinity GD2-specific CAR T cells induce fatal encephalitis in a preclinical neuroblastoma model. Cancer Immunol Res. 2018;6(1):36–46.
   PubMed Web of Science ®Google Scholar
• Rubin DB, Danish HH, Ali AB, et al. Neurological toxicities associated with chimeric antigen receptor T-cell therapy. Brain. 2019;142(5):1334–1348.
   PubMed Web of Science ®Google Scholar
• Mahaley MS, Jr, Bigner DD, Dudka LF, et al. Immunobiology of primary intracranial tumors. Part 7: active immunization of patients with anaplastic human glioma cells: a pilot study. J Neurosurg. 1983a;59(2):201–207.
   PubMed Web of Science ®Google Scholar
• Mahaley MS, Jr, Gillespie GY, Gillespie RP, et al. Immunobiology of primary intracranial tumors. Part 8: serological responses to active immunization of patients with anaplastic gliomas. J Neurosurg. 1983b;59(2):208–216.
   PubMed Web of Science ®Google Scholar
• Zhang JG, Eguchi J, Kruse CA, et al. Antigenic profiling of glioma cells to generate allogeneic vaccines or dendritic cell-based therapeutics. Clin Cancer Res. 2007;13(2 Pt 1):566–575.
   PubMed Web of Science ®Google Scholar
• Ishikawa E, Muragaki Y, Yamamoto T, et al. Phase I/IIa trial of fractionated radiotherapy, temozolomide, and autologous formalin-fixed tumor vaccine for newly diagnosed glioblastoma. J Neurosurg. 2014;121(3):543–553.
   PubMed Web of Science ®Google Scholar
• Muragaki Y, Maruyama T, Iseki H, et al. Phase I/IIa trial of autologous formalin-fixed tumor vaccine concomitant with fractionated radiotherapy for newly diagnosed glioblastoma. Clinical article. JNS. 2011;115(2):248–255.
   PubMed Web of Science ®Google Scholar
• Ishida A, Watanabe M, Matsuo S, et al. Achievement of three year remission in a case of aggressive glioblastoma using a multidisciplinary treatment strategy: a case report. Oncol Lett. 2014;7(5):1608–1612.
   PubMed Web of Science ®Google Scholar
• Larocque A, Hoffman RS. Levamisole in cocaine: unexpected news from an old acquaintance. Clin Toxicol (Phila). 2012;50(4):231–241.
   PubMed Web of Science ®Google Scholar
• Moertel CG, Fleming TR, Macdonald JS, et al. Levamisole and fluorouracil for adjuvant therapy of resected Colon carcinoma. N Engl J Med. 1990;322(6):352–358.
   PubMed Web of Science ®Google Scholar
• Figer A, Nissan A, Shani A, et al. Mature results of a prospective randomized trial comparing 5-flourouracil with leucovorin to 5-Flourouracil with levamisole as adjuvant therapy of stage II and III colorectal Cancer-The Israel Cooperative Oncology Group (ICOG) study. J Cancer. 2011;2:177–185.
   PubMed Web of Science ®Google Scholar
• Hestetun KE, Brydøy M, Myklebust MP, et al. Nuclear maspin expression as a predictive marker for fluorouracil treatment response in Colon cancer. Acta Oncol. 2015;54(4):470–479.
   PubMed Web of Science ®Google Scholar
• Boye K, Jacob H, Frikstad KA, et al. Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population-based series and a randomized phase III study on adjuvant chemotherapy. Cancer Med. 2016;5(8):1840–1849.
   PubMed Web of Science ®Google Scholar
• Mahaley MS, Jr, Steinbok P, Aronin P, et al. Immunobiology of primary intracranial tumors. Part 4: levamisole as an immune stimulant in patients and in the ASV glioma model. J Neurosurg. 1981;54(2):220–227.
   PubMed Web of Science ®Google Scholar
• Fischer SP, Lindermuth J, Hash C, et al. Levamisole in the treatment of glioblastoma multiforme. J Surg Oncol. 1985;28(3):214–216.
   PubMed Web of Science ®Google Scholar
• Romodanov SA, Gnedkova IA, Lisianyĭ NI, et al. Efficacy of chemotherapy and immunochemotherapy in neuro-oncologic patients of various blood groups (ABO system). Zh Vopr Neirokhir Im N N Burdenko. 1989;1:17–20.
   Google Scholar
• Zhang W, Du X, Zhao G, et al. Levamisole is a potential facilitator for the activation of Th1 responses of the subunit HBV vaccination. Vaccine. 2009;27(36):4938–4946.
   PubMed Web of Science ®Google Scholar
• Fabrizi F, Dixit V, Messa P, et al. Meta-analysis: levamisole improves the immune response to hepatitis B vaccine in dialysis patients. Aliment Pharmacol Ther. 2010;32(6):756–762.
   PubMed Web of Science ®Google Scholar
• Sayad B, Alavian SM, Najafi F, et al. Effects of oral levamisole as an adjuvant to hepatitis B vaccine in HIV/AIDS patients: a randomized controlled trial. Hepat Mon. 2012;12(9):e6234.
   PubMed Web of Science ®Google Scholar
• Niu X, Yang Y, Wang J. Synergistic and additive effects of cimetidine and levamisole on cellular immune responses to hepatitis B virus DNA vaccine in mice. Scand J Immunol. 2013;77(2):84–91.
   PubMed Web of Science ®Google Scholar
• Mohanty KC, Vora A, Bendre S, et al. Efficacy and safety of levamisole as an immunomodulator in the treatment of drugresistant tuberculosis. J Assoc Physicians India. 2016;64(1):57–58.
   Google Scholar
• Fu Y, Wang T, Xiu L, et al. Levamisole promotes murine bone marrow derived dendritic cell activation and drives Th1 immune response in vitro and in vivo. Int Immunopharmacol. 2016;31:57–65.
   PubMed Web of Science ®Google Scholar
• Lai X, Pei Q, Song X, et al. The enhancement of immune function and activation of NF-κB by resveratrol-treatment in immunosuppressive mice. Int Immunopharmacol. 2016;33:42–47.
   PubMed Web of Science ®Google Scholar
• Ibrahim HM, Abdel Ghaffar FR, El-Elaimy IA, et al. Antitumor and immune-modulatory efficacy of dual-treatment based on levamisole and/or taurine in ehrlich ascites carcinoma-bearing mice. Biomed Pharmacother. 2018;106:43–49.
   PubMed Web of Science ®Google Scholar
• Gumińska M, Kedryna T, Marchut E. The effect of levamisole on energy metabolism in ehrlich ascites tumour cells in vitro. Biochem Pharmacol. 1986;35(24):4369–4374.
   PubMed Web of Science ®Google Scholar
• Shevchuk I, Chekulayev V, Moan J, et al. Effects of the inhibitors of energy metabolism, lonidamine and levamisole, on 5-aminolevulinic-acid-induced photochemotherapy. Int J Cancer. 1996;67(6):791–799.
   PubMed Web of Science ®Google Scholar
• Elsakka AMA, Bary MA, Abdelzaher E, et al. Management of glioblastoma multiforme in a patient treated with ketogenic metabolic therapy and modified standard of care: a 24-month follow-up. Front Nutr. 2018;5:20.
   PubMed Web of Science ®Google Scholar
• Sun S, Xue D, Chen Z, et al. R406 elicits anti-Warburg effect via syk-dependent and -independent mechanisms to trigger apoptosis in glioma stem cells. Cell Death Dis. 2019;10(5):358.
   PubMed Web of Science ®Google Scholar
• Poff A, Koutnik AP, Egan KM, et al. Targeting the warburg effect for cancer treatment: ketogenic diets for management of glioma. Semin Cancer Biol. 2019;56:135–148.
   PubMed Web of Science ®Google Scholar
• Friis T, Engel AM, Bendiksen CD, et al. Influence of levamisole and other angiogenesis inhibitors on angiogenesis and endothelial cell morphology in vitro. Cancers. 2013;5(3):762–785.
   PubMedGoogle Scholar
• Liu KC, Yo YT, Huang RL, et al. Ovarian cancer stem-like cells show induced translineage-differentiation capacity and are suppressed by alkaline phosphatase inhibitor. Oncotarget. 2013;4(12):2366–2382.
   PubMedGoogle Scholar
• Nageshwari B, Merugu R. Effect of levamisole on expression of CD138 and interleukin-6 in human multiple myeloma cell lines. Indian J Cancer. 2017;54(3):566–571.
   PubMed Web of Science ®Google Scholar
• Qiao X, Wang C, Wang W, et al. Levamisole enhances DR4-independent apoptosis induced by TRAIL through inhibiting the activation of JNK in lung cancer. Life Sci. 2020;257:118034.
   PubMed Web of Science ®Google Scholar
• Vasilogiannakopoulou T, Piperi C, Papavassiliou AG. Impact of aldehyde dehydrogenase activity on gliomas. Trends Pharmacol Sci. 2018;39(7):605–609.
   PubMed Web of Science ®Google Scholar
• Wang YC, Bai MY, Yeh YT, et al. CD133 targeted PVP/PMMA microparticle incorporating levamisole for the treatment of ovarian cancer. Polymers. 2020;12(2):479.
   PubMed Web of Science ®Google Scholar
• Vandevelde M, Boring JG, Hoff EJ, et al. The effect of levamisole on the canine central nervous system. J Neuropathol Exp Neurol. 1978;37(2):165–173.
   PubMed Web of Science ®Google Scholar
• Deracinois B, Duban-Deweer S, Pottiez G, et al. TNAP and EHD1 are over-expressed in bovine brain capillary endothelial cells after the re-induction of blood-brain barrier properties. PLoS One. 2012;7(10):e48428.
   PubMed Web of Science ®Google Scholar
• Deracinois B, Lenfant AM, Dehouck MP, et al. Tissue non-specific alkaline phosphatase (TNAP) in vessels of the brain. Subcell Biochem. 2015;76:125–151.
   PubMedGoogle Scholar
• Yan R, Wu Q, Ren J, et al. Clinical features and magnetic resonance image analysis of 15 cases of demyelinating leukoencephalopathy induced by levamisole. Exp Ther Med. 2013;6(1):71–74.
   PubMed Web of Science ®Google Scholar
• Xu N, Zhou W, Li S, et al. Clinical and MRI characteristics of levamisole-induced leukoencephalopathy in 16 patients. J Neuroimaging. 2009;19(4):326–331.
   PubMed Web of Science ®Google Scholar
• Casacó A, Carvajal D. Interference of levamisole with cerebral edema. Agents Actions. 1990;31(1–2):113–116.
   PubMedGoogle Scholar
• Gonsette RE, Demonty L, Delmotte P, et al. Modulation of immunity in multiple sclerosis: a double-blind levamisole-placebo controlled study in 85 patients. J Neurol. 1982;228(1):65–72.
   PubMed Web of Science ®Google Scholar
• Hoppe B, Makuch-Korulska W, Wasilewski R[, et al. Decaris in the treatment of multiple sclerosis. Neurol Neurochir Pol. 1984;18(3):229–234.
   PubMedGoogle Scholar
• Mukhtarova AA. Comparative analysis of the use of levamisole and pyrogenal in the treatment of multiple sclerosis. Zh Nevropatol Psikhiatr Im S S Korsakova. 1985;85(3):366–367.
   PubMedGoogle Scholar
• Massaro AR, Cioffi RP, Laudisio A, et al. Four year double-blind controlled study of levamisole in multiple sclerosis. Ital J Neurol Sci. 1990;11(6):595–599.
   PubMedGoogle Scholar
• Wender M, Tokarz-Kupczyk E, Mularek O. Late results of alternate treatment of multiple sclerosis with encorton and decaris. Neurol Neurochir Pol. 1991;25(2):149–155.
   PubMedGoogle Scholar
• Agliardi G, Liuzzi AR, Hotblack A, et al. Intratumoral IL-12 delivery empowers CAR-T cell immunotherapy in a pre-clinical model of glioblastoma. Nat Commun. 2021;12(1):444.
   PubMed Web of Science ®Google Scholar
• Wick W, Wagener RJ. Not yet another negative trial-ReACTing on recent glioblastoma trials. Clin Cancer Res. 2020;26(7):1535–1537.
   PubMed Web of Science ®Google Scholar
• Reardon DA, Galanis E, DeGroot JF, et al. Clinical trial end points for high-grade glioma: the evolving landscape. Neuro Oncol. 2011;13(3):353–361.
   PubMed Web of Science ®Google Scholar
• Suh CH, Kim HS, Jung SC, et al. Optimized image-based surrogate endpoints in targeted therapies for glioblastoma: a systematic review and meta-analysis of phase III randomized controlled trials. Korean J Radiol. 2020;21(4):471–482.
   PubMed Web of Science ®Google Scholar
• Lynes J, Sanchez V, Dominah G, et al. Current options and future directions in immune therapy for glioblastoma. Front Oncol. 2018;8:578.
   PubMed Web of Science ®Google Scholar
• Parashar AK, Nema RK. A review on novel techniques for drug delivery to the brain. Curr Res Pharm Sci. 2012;3:134–141.
   Google Scholar