Immunotherapy for Pediatric Gliomas: CAR-T Cells Against B7H3: A
Review of the Literature

Yolanda      Santiago-Vicente; Manuel      de Jesús Castillejos-López; Liliana      Carmona-Aparicio; Elvia      Coballase-Urrutia; Liliana      Velasco-Hidalgo; Ana María      Niembro-Zúñiga; Marta      Zapata-Tarrés; Luz María      Torres-Espíndola
Abstract

Background: B7H3 is a co-stimulatory molecule for immune reactions found on the surface of tumor cells in a wide variety of tumors. Preclinical and clinical studies have reported it as a tumor target towards which various immunotherapy modalities could be directed. So far, good results have been obtained in hematological neoplasms; however, a contrasting situation is evident in solid tumors, including those of the CNS, which show high refractoriness to current treatments. The appearance of cellular immunotherapies has transformed oncology due to the reinforcement of the immune response that is compromised in people with cancer.
Objective: This article aims to review the literature to describe the advancement in knowledge on B7H3 as a target of CAR-T cells in pediatric gliomas to consider them as an alternative in the treatment of these patients.
Results: Although B7H3 is considered a suitable candidate as a target agent for various immunotherapy techniques, there are still limitations in using CAR-T cells to achieve the desired success.
Conclusion: Results obtained with CAR-T cells can be further improved by the suggested proposals; therefore, more clinical trials are needed to study this new therapy in children with gliomas.
[1]
Majzner RG, Theruvath JL, Nellan A, et al. CAR-T Cells targeting B7-H3, a pan-cancer antigen, demonstrate potent preclinical activity against pediatric solid tumors and brain tumors. Clin Cancer Res  2019; 25: 2560-74.

[2]
Thomas P, Galopin N, Bonérandi E, Clémenceau B, Fougeray S, Birklé S. CAR-T cell therapy’s potential for pediatric brain tumors. Cancers  2021; 13: 5445.
 [http://dx.doi.org/10.3390/cancers13215445]

[3]
Chatwin HV, Cruz J, Green AL. Pediatric high-grade glioma: Moving toward subtype-specific multimodal therapy. FEBS J  2021; 288: 6127-41.

[4]
Kendsersky NM, Lindsay J, Kolb EA, et al. The B7-H3-targeting antibody-drug conjugate m276-SL-PBD is potently effective against pediatric cancer preclinical solid tumor models. Clin Cancer Res  2021; 27: 2938-46.
 [http://dx.doi.org/10.1158/1078-0432.CCR-20-4221]

[5]
Wesseling P, Capper D. WHO 2016 Classification of gliomas. Neuropathol Appl Neurobiol  2018; 44(2): 139-50.
 [http://dx.doi.org/10.1111/nan.12432] [PMID:  28815663]

[6]
Bale TA, Rosenblum MK. The 2021 WHO classification of tumors of the central nervous system: An update on pediatric low grade gliomas and glioneuronal tumors. Brain Pathol  2022; 32(4): e13060.
 [http://dx.doi.org/10.1111/bpa.13060] [PMID:  35218102]

[7]
Louis DN, Perry A, Wesseling P. The 2021 WHO classification of tumors of the central nervous system: A summary. Neuro Oncol  2021; 23: 1231-51.

[8]
Jones C, Karajannis MA, Jones DTW, et al. Pediatric high-grade glioma: Biologically and clinically in need of new thinking. Neuro Oncol  2017; 19(2): 153-61.
 [http://dx.doi.org/10.1093/neuonc/noab106] [PMID:  27282398]

[9]
Patterson JD, Henson JC, Breese RO, Bielamowicz KJ, Rodriguez A. CAR-T cell therapy for pediatric brain tumors. Front Oncol  2020; 10: 1582.
 [http://dx.doi.org/10.3389/fonc.2020.01582] [PMID:  32903405]

[10]
Riley RS, June CH, Langer R, Mitchell MJ. Delivery technologies for cancer immunotherapy. Nat Rev Drug Discov  2019; 18(3): 175-96.
 [http://dx.doi.org/10.1038/s41573-018-0006-z] [PMID:  30622344]

[11]
Inoue M, Plautz GE, Shu S. Treatment of intracranial tumors by systemic transfer of superantigen-activated tumor-draining lymph node T cells. Cancer Res  1996; 56(20): 4702-8.
 [PMID:  8840987]

[12]
Filley AC, Henriquez M, Dey M. CART Immunotherapy: Development, Success, and Translation to Malignant Gliomas and Other Solid Tumors. Front Oncol  2018; 8: 453.
 [http://dx.doi.org/10.3389/fonc.2018.00453] [PMID:  30386740]

[13]
Zhang BL, Qin DY, Mo ZM, et al. Hurdles of CAR-T cell-based cancer immunotherapy directed against solid tumors. Sci China Life Sci  2016; 59(4): 340-8.
 [http://dx.doi.org/10.1007/s11427-016-5027-4] [PMID:  26965525]

[14]
June CH, O’Connor RS, Kawalekar OU, Ghassemi S, Milone MC. CAR-T cell immunotherapy for human cancer. Science  2018; 359(6382): 1361-5.
 [http://dx.doi.org/10.1126/science.aar6711] [PMID:  29567707]

[15]
Abbott RC, Cross RS, Jenkins MR. Finding the Keys to the CAR: Identifying Novel Target Antigens for T Cell Redirection Immunotherapies. Int J Mol Sci  2020; 21(2): 515.
 [http://dx.doi.org/10.3390/ijms21020515] [PMID:  31947597]

[16]
Kuwana Y, Asakura Y, Utsunomiya N, et al. Expression of chimeric receptor composed of immunoglobulin-derived V resions and T-cell receptor-derived C regions. Biochem Biophys Res Commun  1987; 149(3): 960-8.
 [http://dx.doi.org/10.1016/0006-291X(87)90502-X] [PMID:  3122749]

[17]
Eshhar Z, Waks T, Gross G, Schindler D. Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. Proc Natl Acad  1993; 90: 720-4.
 [http://dx.doi.org/10.1073/pnas.90.2.720]

[18]
Moritz D, Wels W, Mattern J, Groner B. Cytotoxic T lymphocytes with a grafted recognition specificity for ERBB2-expressing tumor cells. Proc Natl  1994; 91: 4318-22.
 [http://dx.doi.org/10.1073/pnas.91.10.4318]

[19]
Chen L, Flies DB. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol  2013; 13(4): 227-42.
 [http://dx.doi.org/10.1038/nri3405] [PMID:  23470321]

[20]
Haynes NM, Trapani JA, Teng MWL, et al. Single-chain antigen recognition receptors that costimulate potent rejection of established experimental tumors. Blood  2002; 100(9): 3155-63.
 [http://dx.doi.org/10.1182/blood-2002-04-1041] [PMID:  12384413]

[21]
Imai C, Mihara K, Andreansky M, et al. Chimeric receptors with 4-1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia. Leukemia  2004; 18(4): 676-84.
 [http://dx.doi.org/10.1038/sj.leu.2403302] [PMID:  14961035]

[22]
Kawalekar OU, O’Connor RS, Fraietta JA, et al. Distinct signaling of coreceptors regulates specific metabolism pathways and impacts memory development in CAR-T Cells. Immunity  2016; 44(2): 380-90.
 [http://dx.doi.org/10.1016/j.immuni.2016.01.021] [PMID:  26885860]

[23]
Kalos M, Levine BL, Porter DL, et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med  2011; 3(95): 95ra73.
 [http://dx.doi.org/10.1126/scitranslmed.3002842] [PMID:  21832238]

[24]
Long AH, Haso WM, Shern JF, et al. 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors. Nat Med  2015; 21(6): 581-90.
 [http://dx.doi.org/10.1038/nm.3838] [PMID:  25939063]

[25]
Hombach AA, Heiders J, Foppe M, Chmielewski M, Abken H. OX40 costimulation by a chimeric antigen receptor abrogates CD28 and IL-2 induced IL-10 secretion by redirected CD4+T cells. OncoImmunology  2012; 1(4): 458-66.
 [http://dx.doi.org/10.4161/onci.19855] [PMID:  22754764]

[26]
Collinson-Pautz MR, Chang WC, Lu A, et al. Constitutively active MyD88/CD40 costimulation enhances expansion and efficacy of chimeric antigen receptor T cells targeting hematological malignancies. Leukemia  2019; 33(9): 2195-207.
 [http://dx.doi.org/10.1038/s41375-019-0417-9] [PMID:  30816327]

[27]
Guedan S, Chen X, Madar A, et al. ICOS-based chimeric antigen receptors program bipolar TH17/TH1 cells. Blood  2014; 124(7): 1070-80.
 [http://dx.doi.org/10.1182/blood-2013-10-535245] [PMID:  24986688]

[28]
Larson RC, Maus MV. Recent advances and discoveries in the mechanisms and functions of CAR-T cells. Nat Rev Cancer  2021; 21(3): 145-61.
 [http://dx.doi.org/10.1038/s41568-020-00323-z] [PMID:  33483715]

[29]
Chavez JC, Bachmeier C, Kharfan-Dabaja MA. CAR-T-cell therapy for B-cell lymphomas: Clinical trial results of available products. Ther Adv Hematol  2019; 10.
 [http://dx.doi.org/10.1177/2040620719841581] [PMID:  31019670]

[30]
Choi BD, Maus MV, June CH, Sampson JH. Immunotherapy for glioblastoma: Adoptive T-cell strategies. Clin Cancer Res  2019; 25: 2042-8.

[31]
Terry RL, Meyran D, Fleuren EDG, et al. Chimeric Antigen Receptor T cell therapy and the immunosuppressive tumor microenvironment in pediatric sarcoma. Cancers  2021; 13(18): 4704.
 [http://dx.doi.org/10.3390/cancers13184704] [PMID:  34572932]

[32]
Newick K, O’Brien S, Moon E, Albelda SM. CAR-T cell therapy for solid tumors. Annu Rev Med  2017; 68(1): 139-52.
 [http://dx.doi.org/10.1146/annurev-med-062315-120245] [PMID:  27860544]

[33]
Maggs L, Cattaneo G, Dal AE, Moghaddam AS, Ferrone S. CART cell-based immunotherapy for the treatment of glioblastoma. Front Neurosci  2021; 15: 662064.
 [http://dx.doi.org/10.3389/fnins.2021.662064] [PMID:  34113233]

[34]
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): 2561-9.
 [http://dx.doi.org/10.1056/NEJMoa1610497] [PMID:  28029927]

[35]
Bourdeaut F. Are B7-H3 CAR-T cells the future universal treatment for pediatric brain tumors? Neuro Oncol  2021; 23: 872-3.
 [http://dx.doi.org/10.1093/neuonc/noab063]

[36]
Majzner RG, Heitzeneder S, Mackall CL. Harnessing the immunotherapy revolution for the treatment of childhood cancers. Cancer Cell  2017; 31(4): 476-85.
 [http://dx.doi.org/10.1016/j.ccell.2017.03.002] [PMID:  28366678]

[37]
Patel RR, Ramkissoon SH, Ross J, Weintraub L. Tumor mutational burden and driver mutations: Characterizing the genomic landscape of pediatric brain tumors. Pediatr Blood Cancer  2020; 67(7): e28338.
 [http://dx.doi.org/10.1002/pbc.28338] [PMID:  32386112]

[38]
Gill S, Maus MV, Porter DL. Chimeric antigen receptor T cell therapy: 25years in the making. Blood Rev  2016; 30(3): 157-67.
 [http://dx.doi.org/10.1016/j.blre.2015.10.003] [PMID:  26574053]

[39]
Liu B, Yan L, Zhou M. Target selection of CAR-T cell therapy in accordance with the TME for solid tumors. Am J Cancer Res  2019; 9(2): 228-41.
 [PMID:  30906625]

[40]
Petralia F, Tignor N, Reva B, et al. Integrated proteogenomic characterization across major histological types of pediatric brain cancer. Cell  2020; 183(7): 1962-1985.e31.
 [http://dx.doi.org/10.1016/j.cell.2020.10.044] [PMID:  33242424]

[41]
Slaney CY, Kershaw MH, Darcy PK. Trafficking of T cells into tumors. Cancer Res  2014; 74: 7168-4.
 [http://dx.doi.org/10.1158/0008-5472.CAN-14-2458]

[42]
Batista A, Riedemann L, Vardam T, Jain RK. Targeting the tumor microenvironment to enhance pediatric brain cancer treatment. Cancer J  2015; 21: 307-13.
 [http://dx.doi.org/10.1097/PPO.0000000000000125]

[43]
Li D, Li X, Zhou WL, et al. Genetically engineered T cells for cancer immunotherapy. Signal Transduct Target Ther  2019; 4(1): 35.
 [http://dx.doi.org/10.1038/s41392-019-0070-9] [PMID:  31637014]

[44]
Quail DF, Joyce JA. The microenvironmental landscape of brain tumors. Cancer Cell  2017; 31(3): 326-41.
 [http://dx.doi.org/10.1016/j.ccell.2017.02.009] [PMID:  28292436]

[45]
Abbott NJ. Blood-brain barrier structure and function and the challenges for CNS drug delivery. J Inherit Metab Dis  2013; 36(3): 437-49.
 [http://dx.doi.org/10.1007/s10545-013-9608-0] [PMID:  23609350]

[46]
Balda MS, Flores-Maldonado C, Cereijido M, Matter K. Multiple domains of occludin are involved in the regulation of paracellular permeability. J Cell Biochem  2000; 78(1): 85-96.
 [http://dx.doi.org/10.1002/(SICI)1097-4644(20000701)78:1<85:AID-JCB8>3.0.CO;2-F] [PMID:  10797568]

[47]
Pardridge WM. Brain drug development and brain drug targeting. Pharm Res  2007; 24(9): 1729-32.
 [http://dx.doi.org/10.1007/s11095-007-9387-0] [PMID:  17629776]

[48]
Engelhardt B, Ransohoff RM. Capture, crawl, cross: The T cell code to breach the blood–brain barriers. Trends Immunol  2012; 33(12): 579-89.
 [http://dx.doi.org/10.1016/j.it.2012.07.004] [PMID:  22926201]

[49]
Arvanitis CD, Ferraro GB, Jain RK. The blood–brain barrier and blood–tumour barrier in brain tumours and metastases. Nat Rev Cancer  2020; 20(1): 26-41.
 [http://dx.doi.org/10.1038/s41568-019-0205-x] [PMID:  31601988]

[50]
Sarkaria JN, Hu LS, Parney IF, et al. Is the blood-brain barrier really disrupted in all glioblastomas? A critical assessment of existing clinical data. Neuro Oncol  2018; 20(2): 184-91.
 [http://dx.doi.org/10.1093/neuonc/nox175] [PMID:  29016900]

[51]
Merchant TE, Chitti RM, Li C, Xiong X, Sanford RA, Khan RB. Factors associated with neurological recovery of brainstem function following postoperative conformal radiation therapy for infratentorial ependymoma. Int J Radiat Oncol Biol Phys  2010; 76(2): 496-503.
 [http://dx.doi.org/10.1016/j.ijrobp.2009.01.079] [PMID:  19464817]

[52]
Pitz MW, Desai A, Grossman SA, Blakeley JO. Tissue concentration of systemically administered antineoplastic agents in human brain tumors. J Neurooncol  2011; 104(3): 629-38.
 [http://dx.doi.org/10.1007/s11060-011-0564-y] [PMID:  21400119]

[53]
van Tellingen O, Yetkin-Arik B, de Gooijer MC, Wesseling P, Wurdinger T, de Vries HE. Overcoming the blood–brain tumor barrier for effective glioblastoma treatment. Drug Resist Updat  2015; 19: 1-12.
 [http://dx.doi.org/10.1016/j.drup.2015.02.002] [PMID:  25791797]

[54]
Engelhardt B, Wolburg-Buchholz K, Wolburg H. Involvement of the choroid plexus in central nervous system inflammation. Microsc Res Tech  2001; 52(1): 112-29.
 [http://dx.doi.org/10.1002/1097-0029(20010101)52:1<112:AID-JEMT13>3.0.CO;2-5] [PMID:  11135454]

[55]
Chuntova P, Downey KM, Hegde B, Almeida ND, Okada H. Genetically Engineered T-Cells for malignant glioma: Overcoming the barriers to effective immunotherapy. Front Immunol  2019; 9: 3062.
 [http://dx.doi.org/10.3389/fimmu.2018.03062] [PMID:  30740109]

[56]
Donovan LK, Delaidelli A, Joseph SK, et al. Locoregional delivery of CAR-T cells to the cerebrospinal fluid for treatment of metastatic medulloblastoma and ependymoma. Nat Med  2020; 26(5): 720-31.
 [http://dx.doi.org/10.1038/s41591-020-0827-2] [PMID:  32341580]

[57]
Theruvath J, Sotillo E, Mount CW, et al. Locoregionally administered B7-H3-targeted CAR-T cells for treatment of atypical teratoid/rhabdoid tumors. Nat Med  2020; 26(5): 712-9.
 [http://dx.doi.org/10.1038/s41591-020-0821-8] [PMID:  32341579]

[58]
Haydar D, Houke H, Chiang J, et al. Cell-surface antigen profiling of pediatric brain tumors: B7-H3 is consistently expressed and can be targeted via local or systemic CAR-T-cell delivery. Neuro Oncol  2021; 23(6): 999-1011.
 [http://dx.doi.org/10.1093/neuonc/noaa278] [PMID:  33320196]

[59]
Golubovskaya V. Cells targeting immune checkpoint pathway players. Front Biosci  2022; 27(4): 121.
 [http://dx.doi.org/10.31083/j.fbl2704121]

[60]
Cocco C, Morandi F, Airoldi I. Immune checkpoints in pediatric solid tumors: Targetable pathways for advanced therapeutic purposes. Cells  2021; 10(4): 927.
 [http://dx.doi.org/10.3390/cells10040927] [PMID:  33920505]

[61]
Wang Z, Guo X, Gao L, et al. Classification of pediatric gliomas based on immunological profiling: Implications for immunotherapy strategies. Mol Ther Oncolytics  2021; 20: 34-47.
 [http://dx.doi.org/10.1016/j.omto.2020.12.012] [PMID:  33575469]

[62]
Grigor EJM, Fergusson D, Kekre N, et al. Risks and benefits of Chimeric Antigen Receptor T-Cell (CAR-T) therapy in cancer: A systematic review and meta-analysis. Transfus Med Rev  2019; 33(2): 98-110.
 [http://dx.doi.org/10.1016/j.tmrv.2019.01.005] [PMID:  30948292]

[63]
Nicholson JG, Fine HA. Diffuse glioma heterogeneity and its therapeutic implications. Cancer Discov  2021; 11(3): 575-90.
 [http://dx.doi.org/10.1158/2159-8290.CD-20-1474] [PMID:  33558264]

[64]
O’Donnell JS, Teng MWL, Smyth MJ. Cancer immunoediting and resistance to T cell-based immunotherapy. Nat Rev Clin Oncol  2019; 16(3): 151-67.
 [http://dx.doi.org/10.1038/s41571-018-0142-8] [PMID:  30523282]

[65]
Orlando EJ, Han X, Tribouley C, et al. Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia. Nat Med  1504-1506; 2018(24): 30275569.
 [http://dx.doi.org/10.1038/s41591-018-0146] [PMID:  30275569]

[66]
Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol  2004; 22(1): 329-60.
 [http://dx.doi.org/10.1146/annurev.immunol.22.012703.104803] [PMID:  15032581]

[67]
Hamieh M, Dobrin A, Cabriolu A, et al. CAR-T cell trogocytosis and cooperative killing regulate tumour antigen escape. Nature  2019; 568(7750): 112-6.
 [http://dx.doi.org/10.1038/s41586-019-1054-1] [PMID:  30918399]

[68]
Zhang W, Wang Y, Guo Y, et al. Treatment of CD20-directed Chimeric Antigen Receptor-modified T cells in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an early phase IIa trial report. Signal Transduct Target Ther  2016; 1(1): 16002.
 [http://dx.doi.org/10.1038/sigtrans.2016.2] [PMID:  29263894]

[69]
Waibl Polania J, Lerner EC, Wilkinson DS, Hoyt-Miggelbrink A, Fecci PE. Pushing Past the Blockade: Advancements in T Cell-based cancer immunotherapies. Front Immunol  2021; 12: 777073.
 [http://dx.doi.org/10.3389/fimmu.2021.777073] [PMID:  34868044]

[70]
Scharping NE, Rivadeneira DB, Menk AV, et al. Mitochondrial stress induced by continuous stimulation under hypoxia rapidly drives T cell exhaustion. Nat Immunol  2021; 22(2): 205-15.
 [http://dx.doi.org/10.1038/s41590-020-00834-9] [PMID:  33398183]

[71]
Bagley SJ, Desai AS, Linette GP, June CH, O’Rourke DM. CAR-T-cell therapy for glioblastoma: Recent clinical advances and future challenges. Neuro Oncol  2018; 20(11): 1429-38.
 [http://dx.doi.org/10.1093/neuonc/noy032] [PMID:  29509936]

[72]
Collins M, Ling V, Carreno BM. The B7 family of immune-regulatory ligands. Genome Biol  2005; 6(6): 223.
 [http://dx.doi.org/10.1186/gb-2005-6-6-223] [PMID:  15960813]

[73]
Picarda E, Ohaegbulam KC, Zang X. Molecular pathways: Targeting B7-H3 (CD276) for human cancer immunotherapy. Clin Cancer Res  2016; 22: 3431.

[74]
Steinberger P, Majdic O, Derdak SV, et al. Molecular characterization of human 4Ig-B7-H3, a member of the B7 family with four Ig-like domains. J Immunol  2004; 172(4): 2352-9.
 [http://dx.doi.org/10.4049/jimmunol.172.4.2352] [PMID:  14764704]

[75]
Xu H, Cheung IY, Guo HF, Cheung NK. MicroRNA miR-29 modulates expression of immunoinhibitory molecule B7-H3: Potential implications for immune based therapy of human solid tumors. Cancer Res  2009; 69: 6275-6281M.
 [http://dx.doi.org/10.1158/0008-5472.CAN-08-4517]

[76]
Li N, Spetz MR, Li D, Ho M. Advances in immunotherapeutic targets for childhood cancers: A focus on glypican-2 and B7-H3. Pharmacol Ther  2021; 223: 107892.
 [http://dx.doi.org/10.1016/j.pharmthera.2021.107892] [PMID:  33992682]

[77]
He L, Li Z. B7-H3 and its role in bone cancers. Pathol Res Pract  2019; 215(6): 152420.
 [http://dx.doi.org/10.1016/j.prp.2019.04.012] [PMID:  31060912]

[78]
Park JA, Cheung NKV. Targets and antibody formats for immunotherapy of neuroblastoma. J Clin Oncol  2020; 38(16): 1836-48.
 [http://dx.doi.org/10.1200/JCO.19.01410] [PMID:  32167865]

[79]
Ganesan B, Parameswaran S, Sharma A, Krishnakumar S. Clinical relevance of B7H3 expression in retinoblastoma. Sci Rep  2020; 10(1): 10185.
 [http://dx.doi.org/10.1038/s41598-020-67101-7] [PMID:  32576886]

[80]
Du H, Hirabayashi K, Ahn S, et al. Antitumor responses in the absence of toxicity in solid tumors by targeting B7-H3 via chimeric antigen receptor T cells. Cancer Cell  2019; 35(2): 221-37.
 [http://dx.doi.org/10.1016/j.ccell.2019.01.002] [PMID:  30753824]

[81]
Zhang Z, Jiang C, Liu Z, et al. B7-H3-targeted CAR-T cells exhibit potent antitumor effects on hematologic and solid tumors. Mol Ther Oncolytics  2020; 17: 180-9.
 [http://dx.doi.org/10.1016/j.omto.2020.03.019] [PMID:  32346608]

[82]
Zhou WT, Jin WL. B7-H3/CD276: An emerging cancer immunotherapy. Front Immunol  2021; 12: 701006.
 [http://dx.doi.org/10.3389/fimmu.2021.701006] [PMID:  34349762]

[83]
Maachani UB, Tosi U, Pisapia DJ, et al. B7–H3 as a prognostic biomarker and therapeutic target in pediatric central nervous system tumors. Transl Oncol  2020; 13(2): 365-71.
 [http://dx.doi.org/10.1016/j.tranon.2019.11.006] [PMID:  31887631]

[84]
Lee Y, Martin-Orozco N, Zheng P, et al. Inhibition of the B7-H3 immune checkpoint limits tumor growth by enhancing cytotoxic lymphocyte function. Cell Res  2017; 27(8): 1034-45.
 [http://dx.doi.org/10.1038/cr.2017.90] [PMID:  28685773]

[85]
Ueno T, Yeung MY, McGrath M, et al. Intact B7-H3 signaling promotes allograft prolongation through preferential suppression of Th1 effector responses. Eur J Immunol  2012; 42(9): 2343-53.
 [http://dx.doi.org/10.1002/eji.201242501] [PMID:  22733595]

[86]
Chapoval AI, Ni J, Lau JS, et al. B7-H3: A costimulatory molecule for T cell activation and IFN-γ production. Nat Immunol  2001; 2(3): 269-74.
 [http://dx.doi.org/10.1038/85339] [PMID:  11224528]

[87]
Kontos F, Michelakos T, Kurokawa T, et al. B7-H3: An attractive target for antibody-based immunotherapy. Clin Cancer Res  2021; 27: 1227-35.

[88]
Castellanos JR, Purvis IJ, Labak CM, et al. B7-H3 role in the immune landscape of cancer. Am J Clin Exp Immunol  2017; 6(4): 66-75.
 [PMID:  28695059]

[89]
Zhong C, Tao B, Chen Y, et al. B7-H3 regulates glioma growth and cell invasion through a JAK2/STAT3/Slug-dependent signaling pathway. OncoTargets Ther  2020; 13: 2215-24.
 [http://dx.doi.org/10.2147/OTT.S237841] [PMID:  32210587]

[90]
Huang J, Zheng M, Zhang Z, et al. Interleukin-7-loaded oncolytic adenovirus improves CAR-T cell therapy for glioblastoma. Cancer Immunol Immunother  2021; 70(9): 2453-65.
 [http://dx.doi.org/10.1007/s00262-021-02856-0] [PMID:  33543339]

[91]
Wang Z, Yang J, Zhu Y, Zhu Y, Zhang B, Zhou Y. Differential expression of 2IgB7-H3 and 4IgB7-H3 in cancer cell lines and glioma tissues. Oncol Lett  2015; 10(4): 2204-8.
 [http://dx.doi.org/10.3892/ol.2015.3611] [PMID:  26622819]

[92]
Chang L. Targeting CD276 (B7H3) Positive Solid Tumors by 4SCAR276 2020.NCT 04432649, 

[93]
Gardner R. Study of B7H3 specific CART cell locorregional immunotherapy for diffuse intrinsic pontine glioma/diffuse midline glioma and recurrent or refractary pediatric central nervous system tummors 2019.NCT 04185038, 

[94]
Lei X, Ou Z, Yang Z, et al. A pan-histone deacetylase inhibitor enhances the antitumor activity of B7-H3–Specific CAR-T cells in solid tumors. Clin Cancer Res  2021; 27(13): 3757-71.
 [http://dx.doi.org/10.1158/1078-0432.CCR-20-2487] [PMID:  33811153]

[95]
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. Theranostics  2020; 10(17): 7622-34.
 [http://dx.doi.org/10.7150/thno.43991] [PMID:  32685008]

[96]
Lu-Emerson C, Duda DG, Emblem KE, et al. Lessons from anti-vascular endothelial growth factor and anti-vascular endothelial growth factor receptor trials in patients with glioblastoma. J Clin Oncol  2015; 33(10): 1197-213.
 [http://dx.doi.org/10.1200/JCO.2014.55.9575] [PMID:  25713439]

[97]
Marofi F, Motavalli R, Safonov VA, et al. CAR-T cells in solid tumors: Challenges and opportunities. Stem Cell Res Ther  2021; 12(1): 81.
 [http://dx.doi.org/10.1186/s13287-020-02128-1] [PMID:  33494834]

[98]
Loskog A, Giandomenico V, Rossig C, Pule M, Dotti G, Brenner MK. Addition of the CD28 signaling domain to chimeric T-cell receptors enhances chimeric T-cell resistance to T regulatory cells. Leukemia  2006; 20(10): 1819-28.
 [http://dx.doi.org/10.1038/sj.leu.2404366] [PMID:  16932339]

[99]
Chmielewski M, Kopecky C, Hombach AA, Abken H. IL-12 release by engineered T cells expressing chimeric antigen receptors can effectively Muster an antigen-independent macrophage response on tumor cells that have shut down tumor antigen expression. Cancer Res  2011; 71(17): 5697-706.
 [http://dx.doi.org/10.1158/0008-5472.CAN-11-0103] [PMID:  21742772]

[100]
Xu J, Zhang Q, Tian K, Wang H, Yin H, Zheng J. Current status and future prospects of the strategy of combining CAR T with PD 1 blockade for antitumor therapy. Mol Med Rep  2017; 17(2): 2083-8.
 [http://dx.doi.org/10.3892/mmr.2017.8129] [PMID:  29207115]

[101]
Zhou X, Brenner MK. Improving the safety of T-Cell therapies using an inducible caspase-9 gene. Exp Hematol  2016; 44(11): 1013-9.
 [http://dx.doi.org/10.1016/j.exphem.2016.07.011] [PMID:  27473568]

[102]
Srivastava S, Furlan SN, Jaeger-Ruckstuhl CA, et al. Immunogenic chemotherapy enhances recruitment of CAR-T cells to lung tumors and improves antitumor efficacy when combined with checkpoint blockade. Cancer Cell  2021; 39(2): 193-208.e10.
 [http://dx.doi.org/10.1016/j.ccell.2020.11.005] [PMID:  33357452]

[103]
Nadella V, Singh S, Jain A, et al. Low dose radiation primed iNOS + M1macrophages modulate angiogenic programming of tumor derived endothelium. Mol Carcinog  2018; 57(11): 1664-71.
 [http://dx.doi.org/10.1002/mc.22879] [PMID:  30035346]

[104]
Gholamin S, Mitra SS, Feroze AH, et al. Disrupting the CD47-SIRPα anti-phagocytic axis by a humanized anti-CD47 antibody is an efficacious treatment for malignant pediatric brain tumors. Sci Transl Med  2017; 9(381): eaaf2968.
 [http://dx.doi.org/10.1126/scitranslmed.aaf2968] [PMID:  28298418]

[105]
Murty S, Haile ST, Beinat C, et al. Intravital imaging reveals synergistic effect of CAR-T-cells and radiation therapy in a preclinical immunocompetent glioblastoma model. OncoImmunology  2020; 9: 1757360.

[106]
Rafiq S, Hackett CS, Brentjens RJ. Engineering strategies to overcome the current roadblocks in CAR-T cell therapy. Nat Rev Clin Oncol  2020; 17(3): 147-67.
 [http://dx.doi.org/10.1038/s41571-019-0297-y] [PMID:  31848460]

[107]
Sukumar M, Liu J, Ji Y, et al. Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function. J Clin Invest  2013; 123(10): 4479-88.
 [http://dx.doi.org/10.1172/JCI69589] [PMID:  24091329]

[108]
Stockwell J, Jakova E, Cayabyab F. Adenosine A1 and A2A Receptors in the Brain: Current research and their role in neurodegeneration. Molecules  2017; 22(4): 676.
 [http://dx.doi.org/10.3390/molecules22040676] [PMID:  28441750]

[109]
Nabe S, Yamada T, Suzuki J, et al. Reinforce the antitumor activity of CD8+ T cells via glutamine restriction. Cancer Sci  2018; 109(12): 3737-50.
 [http://dx.doi.org/10.1111/cas.13827] [PMID:  30302856]

[110]
Souweidane MM, Kramer K, Pandit-Taskar N, et al. Convection-enhanced delivery for diffuse intrinsic pontine glioma: A single-centre, dose-escalation, phase 1 trial. Lancet Oncol  2018; 19(8): 1040-50.
 [http://dx.doi.org/10.1016/S1470-2045(18)30322-X] [PMID:  29914796]

[111]
Ligtenberg MA, Mougiakakos D, Mukhopadhyay M, et al. Coexpressed catalase protects chimeric antigen receptor-redirected T cells as well as bystander cells from oxidative stress-induced loss of antitumor activity. J Immunol  2016; 196(2): 759-66.
 [http://dx.doi.org/10.4049/jimmunol.1401710] [PMID:  26673145]

[112]
Caruana I, Savoldo B, Hoyos V, Weber G, Liu H, Kim ES. Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes. Nat Med  2015; 21: 524-9.
Cite As
CNS & Neurological Disorders - Drug Targets

Immunotherapy for Pediatric Gliomas: CAR-T Cells Against B7H3: A Review of the Literature

Abstract
