The Role of CD276 in Cancers

Kan Wu+3 authors

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^{Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China,}

^{William Harvey Research Institute, Queen Mary University of London, London, United Kingdom,}

^{Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China,}

^{Clinical Science and Services, Royal Veterinary College, University of London, London, United Kingdom,}

Edited by: Andrew Zloza, Rush University Medical Center, United States

Reviewed by: Ivana De La Serna, University of Toledo Medical Center, United States; Barbara Muz, Washington University in St. Louis, United States

*Correspondence: Yiping Lu, moc.621@hcw_gnipiyul; Xianding Wang, moc.kooltuo@gnawgnidnaix

†ORCID: Shengzhuo Liu, 0000-0001-8424-2549; Yiping Lu, 0000-0003-1541-2879; Xianding Wang, 0000-0002-5780-5622

‡These authors have contributed equally to this work

This article was submitted to Cancer Molecular Targets and Therapeutics, a section of the journal Frontiers in Oncology

Edited by: Andrew Zloza, Rush University Medical Center, United States

Reviewed by: Ivana De La Serna, University of Toledo Medical Center, United States; Barbara Muz, Washington University in St. Louis, United States

Received 2021 Jan 17; Accepted 2021 Mar 2.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Abstract

Objective

Aberrant expression of the immune checkpoint molecule, CD276, also known as B7-H3, is associated with tumorigenesis. In this review, we aim to comprehensively describe the role of CD276 in malignancies and its potential therapeutic effect.

Data Sources

Database including PubMed, EMbase, Cochrane Library, CNKI, and Clinical Trails.gov were searched for eligible studies and reviews. Study selection: Original studies and review articles on the topic of CD276 in tumors were retrieved.

Results

CD276 is an immune checkpoint molecule in the epithelial mesenchymal transition (EMT) pathway. In this review, we evaluated the available evidence on the expression and regulation of CD276. We also assessed the role of CD276 within the immune micro-environment, effect on tumor progression, and the potential therapeutic effect of CD276 targeted therapy for malignancies.

Conclusion

CD276 plays an essential role in cell proliferation, invasion, and migration in malignancies. Results from most recent studies indicate CD276 could be a promising therapeutic target for malignant tumors.

Keywords: CD276, B7-H3, therapeutic target, tumor, progression

Abstract

MGD009: B7-H3 x CD3 DART protein, is also known as orlotamab.

MGC018: Anti-B7-H3 antibody drug conjugate.

MGA012: Anti-PD-1 antibody, is also known as INCMGA00012.

MGA271: is also known as enoblituzumab.

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References

1. Flem-Karlsen K, Fodstad Ø, Tan M, Nunes-Xavier CE. B7-H3 in cancer–beyond immune regulation. Trends Cancer (2018) 4:401–4. 10.1016/j.trecan.2018.03.010 [] [[PubMed]
2. Chapoval AI, Ni J, Lau JS, Wilcox RA, Flies DB, Liu D, et al. . B7-H3: a costimulatory molecule for T cell activation and IFN-γ production. Nat Immunol (2001) 2:269–74. 10.1038/85339 [] [[PubMed]
3. Xylinas E, Robinson B, Kluth L, Volkmer BG, Hautmann R, Küfer R, et al. . Association of T-cell co-regulatory protein expression with clinical outcomes following radical cystectomy for urothelial carcinoma of the bladder. Eur J Surg Oncol (2014) 40:121–7. 10.1016/j.ejso.2013.08.023 [] [[PubMed]
4. Brunner A, Hinterholzer S, Riss P, Heinze G, Brustmann H. Immunoexpression of B7-H3 in endometrial cancer: relation to tumor T-cell infiltration and prognosis. Gynecol Oncol (2012) 124:105–11. 10.1016/j.ygyno.2011.09.012 [] [[PubMed]
5. Zhao X, Li D-C, Zhu X-G, Gan W-J, Li Z, Xiong F, et al. . B7-H3 overexpression in pancreatic cancer promotes tumor progression. Int J Mol Med (2013) 31:283–91. 10.3892/ijmm.2012.1212 ] [
6. Yamato I, Sho M, Nomi T, Akahori T, Shimada K, Hotta K, et al. . Clinical importance of B7-H3 expression in human pancreatic cancer. Br J Cancer (2009) 101:1709–16. 10.1038/sj.bjc.6605375 ] [
7. Huang C, Zhou L, Chang X, Pang X, Zhang H, Zhang S. B7-H3, B7-H4, Foxp3 and IL-2 expression in cervical cancer: Associations with patient outcome and clinical significance. Oncol Rep (2016) 35:2183–90. 10.3892/or.2016.4607 [] [[PubMed]
8. Maeda N, Yoshimura K, Yamamoto S, Kuramasu A, Inoue M, Suzuki N, et al. . Expression of B7-H3, a potential factor of tumor immune evasion in combination with the number of regulatory T cells, affects against recurrence-free survival in breast cancer patients. Ann Surg Oncol (2014) 21:546–54. 10.1245/s10434-014-3564-2 ] [
9. Arigami T, Narita N, Mizuno R, Nguyen L, Ye X, Chung A, et al. . B7–H3 ligand expression by primary breast cancer and associated with regional nodal metastasis. Ann Surg Oncol (2010) 252:1044–51. 10.1097/SLA.0b013e3181f1939d [] [[PubMed]
10. Cheng R, Chen Y, Zhou H, Wang B, Du Q, Chen Y. B7-H3 expression and its correlation with clinicopathologic features, angiogenesis, and prognosis in intrahepatic cholangiocarcinoma. APMIS (2018) 126:396–402. 10.1111/apm.12837 [] [[PubMed]
11. Ingebrigtsen VA, Boye K, Tekle C, Nesland JM, Flatmark K, Fodstad O, et al. . B7-H3 expression in colorectal cancer: nuclear localization strongly predicts poor outcome in colon cancer. Int J Cancer (2012) 131:2528–36. 10.1002/ijc.27566 [] [[PubMed]
12. Zang X, Sullivan PS, Soslow RA, Waitz R, Reuter VE, Wilton A, et al. . Tumor associated endothelial expression of B7-H3 predicts survival in ovarian carcinomas. Mod Pathol (2010) 23:1104–12. 10.1038/modpathol.2010.95 ] [
13. Zhou Z, Luther N, Ibrahim GM, Hawkins C, Vibhakar R, Handler MH, et al. . B7-H3, a potential therapeutic target, is expressed in diffuse intrinsic pontine glioma. J Neurooncol (2013) 111:257–64. 10.1007/s11060-012-1021-2 ] [
14. Wang J, Chong KK, Nakamura Y, Nguyen L, Huang SK, Kuo C, et al. . B7-H3 associated with tumor progression and epigenetic regulatory activity in cutaneous melanoma. J Invest Dermatol (2013) 133:2050–8. 10.1038/jid.2013.114 ] [
15. Inamura K, Yokouchi Y, Kobayashi M, Sakakibara R, Ninomiya H, Subat S, et al. . Tumor B7-H3 (CD276) expression and smoking history in relation to lung adenocarcinoma prognosis. Lung Cancer (2016) 243:21–8. 10.1016/j.lungcan.2016.09.016 [] [[PubMed]
16. Sun Y, Wang Y, Zhao J, Gu M, Giscombe R, Lefvert AK, et al. . B7-H3 and B7-H4 expression in non-small-cell lung cancer. Lung Cancer (2006) 53:143–51. 10.1016/j.lungcan.2006.05.012 [] [[PubMed]
17. Sun T-W, Gao Q, Qiu S-J, Zhou J, Wang XY, Yi Y, et al. . B7-H3 is expressed in human hepatocellular carcinoma and is associated with tumor aggressiveness and postoperative recurrence. Cancer Immunol Immunother (2012) 61:2171–82. 10.1007/s00262-012-1278-5 [] [[PubMed]
18. Zang X, Thompson RH, Al-Ahmadie HA, Serio AM, Reuter VE, Eastham JA, et al. . B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome. Proc Natl Acad Sci USA (2007) 104:19458–63. 10.1073/pnas.0709802104 ] [
19. Benzon B, Zhao S, Haffner M, Takhar M, Erho N, Yousefi K, et al. . Correlation of B7-H3 with androgen receptor, immune pathways and poor outcome in prostate cancer: an expression-based analysis. Prostate Cancer Prostatic Dis (2017) 20:28–35. 10.1038/pcan.2016.49 ] [
20. Chen J-T, Chen C-H, Ku K-L, Hsiao M, Chiang CP, Hsu TL, et al. . Glycoprotein B7-H3 overexpression and aberrant glycosylation in oral cancer and immune response. Proc Natl Acad Sci USA (2015) 112:13057–62. 10.1073/pnas.1516991112 ] [
21. Crispen PL, Sheinin Y, Roth TJ, Lohse CM, Kuntz SM, Frigola X, et al. . Tumor cell and tumor vasculature expression of B7-H3 predict survival in clear cell renal cell carcinoma. Clin Cancer Res (2008) 14:5150–7. 10.1158/1078-0432.CCR-08-0536 ] [
22. Loos M, Hedderich DM, Ottenhausen M, Giese NA, Laschinger M, Esposito I, et al. . Expression of the costimulatory molecule B7-H3 is associated with prolonged survival in human pancreatic cancer. BMC Cancer (2009) 9:1–10. 10.1186/1471-2407-9-463 ] [
23. Dai W, Shen G, Qiu J, Zhao X, Gao Q. Aberrant expression of B7-H3 in gastric adenocarcinoma promotes cancer cell metastasis. Oncol Rep (2014) 32:2086–92. 10.3892/or.2014.3405 [] [[PubMed]
24. Liang J, Liu Z, Pei T, Xiao Y, Zhou L, Tang Y, et al. . Clinicopathological and Prognostic Characteristics of CD276 (B7-H3) Expression in Adrenocortical Carcinoma. Dis Markers (2020) 2020:5354825. 10.1155/2020/5354825 ] [
25. Seaman S, Zhu Z, Saha S, Zhang XM, Yang MY, Hilton MB, et al. . Eradication of tumors through simultaneous ablation ofCD276/B7-H3-positive tumor cells and tumor vasculature. Cancer Cell(2017) 31:501–15.e508. 10.1016/j.ccell.2017.03.005 ] [
26. Flem-Karlsen K, Fodstad Ø, Nunes-Xavier CE, et al. . B7-H3 Immune Checkpoint Protein in Human Cancer.Curr Med Chem (2020)27(24):4062–86. 10.2174/0929867326666190517115515 [] [[PubMed]
27. Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu Rev Immunol (2005) 23:515–48. 10.1146/annurev.immunol.23.021704.115611 [] [[PubMed]
28. Yi KH, Chen LJIR. Fine tuning the immune response through B7-H3 and B7-H4. Immunol Rev (2009) 229:145–51. 10.1111/j.1600-065X.2009.00768.x ] [
29. Hofmeyer KA, Ray A, Zang X. The contrasting role of B7-H3. Proc Natl Acad Sci USA (2008) 105:10277–8. 10.1073/pnas.0805458105 ] [
30. Suh W-K, Gajewska BU, Okada H, Gronski MA, Bertram EM, Dawicki W, et al. . The B7 family member B7-H3 preferentially down-regulates T helper type 1–mediated immune responses. Nat Immunol (2003) 4:899–906. 10.1038/ni967 [] [[PubMed]
31. Shevach EM, McHugh RS, Piccirillo CA, Thornton AM. Control of T-cell activation by CD4+ CD25+ suppressor T cells. Immunol Rev (2001) 182:58–67. 10.1034/j.1600-065X.2001.1820104.x [] [[PubMed]
32. Mahnke K, Ring S, Johnson TS, Schallenberg S, Schönfeld K, Storn V, et al. . Induction of immunosuppressive functions of dendritic cells in vivo by CD4+ CD25+ regulatory T cells: role of B7-H3 expression and antigen presentation. Eur J Immunol (2007) 37:2117–26. 10.1002/eji.200636841 [] [[PubMed]
33. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell (2004) 116:281–97. 10.1016/S0092-8674(04)00045-5 [] [[PubMed]
34. Dong P, Xiong Y, Yue J, Hanley SJB, Watari H. B7H3 as a promoter of metastasis and promising therapeutic target. Front Oncol (2018) 8:264. 10.3389/fonc.2018.00264 ] [
35. Bing G HC, Zhengpeng S. MiR-29a inhibited costimulatory molecule B7-H3 expression and theinvasion of glioma growth. Chin J Cancer Biother (2015) 22:28–33. 10.3872/j.issn.1007-385X.2015.1.005 [[PubMed]
36. Xu H, Cheung IY, Guo H-F, Cheung N-KV. MicroRNA miR-29 modulates expression of immunoinhibitory molecule B7-H3: potential implications for immune based therapy of human solid tumors. Cancer Res (2009) 69:6275–81. 10.1158/0008-5472.CAN-08-4517 ] [
37. Colonna M, Nakajima H, Cella M. A family of inhibitory and activating Ig-like receptors thatmodulate function of lymphoid and myeloid cells. Semin Immunol.(2000) 12(2):121–7. 10.1006/smim.2000.0214 [] [[PubMed]
38. Zhang P, Yu S, Li H, Liu C, Li J, Lin W, et al. . ILT4 drives B7-H3 expression via PI3K/AKT/mTOR signalling and ILT4/B7-H3 co-expression correlates with poor prognosis in non-small cell lung cancer. FEBS Lett (2015) 589:2248–56. 10.1016/j.febslet.2015.06.037 [] [[PubMed]
39. Wang M-Y, Qi B, Wang F, Li MY, Yin WJ. PBK phosphorylates MSL1 to elicit epigenetic modulation of CD276 in nasopharyngeal carcinoma. Oncogenesis (2021) 10:9. 10.1038/s41389-020-00293-9 ] [
40. Linsley PS, Greene JL, Brady W, Bajorath J, Ledbetter JA, Peach R. Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. Immunity (1994) 1:793–801. 10.1016/S1074-7613(94)80021-9 [] [[PubMed]
41. Brandt CS, Baratin M, Yi EC, Kennedy J, Gao Z, Fox B, et al. . The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans. J Exp Med (2009) 206:1495–503. 10.1084/jem.20090681 ] [
42. Hashiguchi M, Kobori H, Ritprajak P, Kamimura Y, Kozono H, Azuma M, et al. . Triggering receptor expressed on myeloid cell-like transcript 2 (TLT-2) is a counter-receptor for B7-H3 and enhances T cell responses. Proc Natl Acad Sci USA (2008) 105:10495–500. 10.1073/pnas.0802423105 ] [
43. Hashiguchi M, Inamochi Y, Nagai S, Otsuki N, Piao J, Kobori H, et al. . Human B7-H3 binds to Triggering receptor expressed on myeloid cells-like transcript 2 (TLT-2) and enhances T cell responses. Open J Immunol (2012) 2:9. 10.4236/oji.2012.21002 [[PubMed]
44. Leitner J, Klauser C, Pickl WF, Stöckl J, Majdic O, Bardet AF, et al. . B7-H3 is a potent inhibitor of human T-cell activation: no evidence for B7-H3 and TREML2 interaction. Eur J Immunol (2009) 39:1754–64. 10.1002/eji.200839028 ] [
45. Vigdorovich V, Ramagopal UA, Lázár-Molnár E, Sylvestre E, Lee JS, Hofmeyer KA, et al. . Structure and T cell inhibition properties of B7 family member, B7-H3. Structure (2013) 21:707–17. 10.1016/j.str.2013.03.003 ] [
46. Husain B, Ramani SR, Chiang E, Lehoux I, Paduchuri S, Arena TA, et al. . A platform for extracellular interactome discovery identifies novel functional binding partners for the immune receptors B7-H3/CD276 and PVR/CD155. Mol Cell Proteomics (2019) 18:2310–23. 10.1074/mcp.TIR119.001433 ] [
47. Loos M, Hedderich DM, Friess H, Kleeff J. B7-h3 and its role in antitumor immunity.Clin Dev Immunol (2010) 2010:683875. 10.1155/2010/683875 ] [
48. Ma J, Ma P, Zhao C, Xue X, Han H, Liu C, et al. . B7-H3 as a promising target for cytotoxicity T cell in human cancer therapy. Oncotarget (2016) 7:29480. 10.18632/oncotarget.8784 ] [
49. Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J (1992) 11:3887–95. 10.1002/j.1460-2075.1992.tb05481.x ] [
50. Agata Y, Kawasaki A, Nishimura H, Ishida Y, Tsubata T, Yagita H, et al. . Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. Int Immunol (1996) 8:765–72. 10.1093/intimm/8.5.765 [] [[PubMed]
51. Butte MJ, Keir ME, Phamduy TB, Sharpe AH, Freeman GJ. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity (2007) 27:111–22. 10.1016/j.immuni.2007.05.016 ] [
52. Mischinger J, Comperat E, Schwentner C, Stenzl A, Gakis G. Inflammation and cancer: what can we therapeutically expect from checkpoint inhibitors? Curr Urol Rep (2015) 16:1–6. 10.1007/s11934-015-0532-8 [] [[PubMed]
53. Bao R, Wang Y, Lai J, Zhu H, Zhao Y, Li S, et al. . Enhancing anti-PD-1/PD-L1 immune checkpoint inhibitory cancer therapy by CD276-targeted photodynamic ablation of tumor cells and tumor vasculature. Mol Pharm (2018) 16:339–48. 10.1021/acs.molpharmaceut.8b00997 [] [[PubMed]
54. Linsley PS, Bradshaw J, Greene J, Peach R, Bennett KL, Mittler RS. Intracellular trafficking of CTLA-4 and focal localization towards sites of TCR engagement. Immunity (1996) 4:535–43. 10.1016/S1074-7613(00)80480-X [] [[PubMed]
55. Ewing M, Karper J, Abdul S, de Jong RC, Peters HA, de Vries MR, et al. . T-cell co-stimulation by CD28–CD80/86 and its negative regulator CTLA-4 strongly influence accelerated atherosclerosis development. Int J Cardiol (2013) 168:1965–74. 10.1016/j.ijcard.2012.12.085 [] [[PubMed]
56. Goronzy JJ, Weyand CM. T-cell co-stimulatory pathways in autoimmunity. Arthritis Res Ther (2008) 10:1–10. 10.1186/ar2414 ] [
57. Coussens LM, Werb ZJN. Inflammation and cancer. Nature (2002) 420:860–7. 10.1038/nature01322 ] [
58. Egen JG, Kuhns MS, Allison JP. CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nat Immunol (2002) 3:611–8. 10.1038/ni0702-611 [] [[PubMed]
59. Schneider H, Downey J, Smith A, Zinselmeyer BH, Rush C, Brewer JM, et al. . Reversal of the TCR stop signal by CTLA-4. Science (2006) 313:1972–5. 10.1126/science.1131078 [] [[PubMed]
60. Picarda E, Ohaegbulam KC, Zang XJ. Molecular pathways: targeting B7-H3 (CD276) for human cancer immunotherapy. Clin Cancer Res (2016) 22:3425–31. 10.1158/1078-0432.CCR-15-2428 ] [
61. Lim S, Liu H, Da Silva LM, Arora R, Liu Z, Phillips JB, et al. . Immunoregulatory protein B7-H3 reprograms glucose metabolism in cancer cells by ROS-mediated stabilization of HIF1α. Cancer Res (2016) 76:2231–42. 10.1158/0008-5472.CAN-15-1538 ] [
62. Tekle C, Nygren MK, Chen YW, Dybsjord I, Nesland JM, Maelandsmo GM, et al. . B7-H3 contributes to the metastatic capacity of melanoma cells by modulation of known metastasis-associated genes. Int J Cancer (2012) 130:2282–90. 10.1002/ijc.26238 [] [[PubMed]
63. Kang F-B, Wang L, Jia H-C, Li D, Li HJ, Zhang YG, et al. . B7-H3 promotes aggression and invasion of hepatocellular carcinoma by targeting epithelial-to-mesenchymal transition via JAK2/STAT3/Slug signaling pathway. Cancer Cell Int (2015) 15:1–11. 10.1186/s12935-015-0195-z ] [
64. Zhang J, Wang J, Marzese DM, Wang X, Yang Z, Li C, et al. . B7H3 regulates differentiation and serves as a potential biomarker and theranostic target for human glioblastoma. Lab Invest (2019) 99:1117–29. 10.1038/s41374-019-0238-5 [] [[PubMed]
65. Li Y, Yang X, Yao P, Shen W, Wu Y, Ye Z, et al. . B7-H3 increases the radioresistance of gastric cancer cells through regulating baseline levels of cell autophagy. Am J Transl Res (2019) 11(7):4438–49.
66. McDougall SR, Anderson AR, Chaplain MA. Mathematical modelling of dynamic adaptive tumour-induced angiogenesis: clinical implications and therapeutic targeting strategies. J Theor Biol (2006) 241:564–89. 10.1016/j.jtbi.2005.12.022 [] [[PubMed]
67. Ricci-Vitiani L, Pallini R, Biffoni M, Todaro M, Invernici G, Cenci T, et al. . Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells. Nature (2010) 468:824–8. 10.1038/nature09557 [] [[PubMed]
68. Wang R, Chadalavada K, Wilshire J, Kowalik U, Hovinga KE, Geber A, et al. . Glioblastoma stem-like cells give rise to tumour endothelium. Nature (2010) 468:829–33. 10.1038/nature09624 [] [[PubMed]
69. Xie C, Liu D, Chen Q, Yang C, Wang B, Wu H. Soluble B7-H3 promotes the invasion and metastasis of pancreatic carcinoma cells through the TLR4/NF-κB pathway. Sci Rep (2016) 6:1–9. 10.1038/srep27528 ] [
70. Lai H, Sun Z, Yang J, Wu P, Guo Y, Sun J. B7-H3 modulates endothelial cell angiogenesis through the VEGF cytokine. Immunol Res (2019) 67:202–11. 10.1007/s12026-019-09084-w [] [[PubMed]
71. Ferrara N. VEGF and the quest for tumour angiogenesis factors. Nat Rev Cancer (2002) 2:795–803. 10.1038/nrc909 [] [[PubMed]
72. Li G, Quan Y, Che F, Wang L. B7-H3 in tumors: friend or foe for tumor immunity? Cancer Chemother Pharmacol (2018) 81:245–53. 10.1007/s00280-017-3508-1 [] [[PubMed]
73. Castellanos JR, Purvis IJ, Labak CM, Guda MR, Tsung AJ, Velpula KK, et al. . B7-H3 role in the immune landscape of cancer. Am J Clin Exp Immunol (2017) 6(4):66– 75.
74. Lupu CM, Eisenbach C, Lupu AD, Kuefner MA, Hoyler B, Stremmel W, et al. . Adenoviral B7-H3 therapy induces tumor specific immune responses and reduces secondary metastasis in a murine model of colon cancer. Oncol Rep (2007) 18:745–8. 10.3892/or.18.3.745 [] [[PubMed]
75. Yang HY, Chu M, Zheng LW, Zwahlen RA, Luo J, Zou DH, et al. . Transgenic B7-H3 therapy induces tumor-specific immune response in human oral squamous cell cancer: an in vitro study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod (2008) 106:721–8. 10.1016/j.tripleo.2008.08.012 [] [[PubMed]
76. Ma L, Luo L, Qiao H, Dong X, Pan S, Jiang H, et al. . Complete eradication of hepatocellular carcinomas by combined vasostatin gene therapy and B7H3-mediated immunotherapy. J Hepatol (2007) 46:98–106. 10.1016/j.jhep.2006.07.031 [] [[PubMed]
77. Loo D, Alderson RF, Chen FZ, Huang L, Zhang W, Gorlatov S, et al. . Development of an Fc-enhanced anti–B7-H3 monoclonal antibody with potent antitumor activity. Clin Cancer Res (2012) 18:3834–45. 10.1158/1078-0432.CCR-12-0715 [] [[PubMed]
78. Fauci JM, Sabbatino F, Wang Y, Londoño-Joshi AI, Straughn JM, Jr., Landen CN, et al. . Monoclonal antibody-based immunotherapy of ovarian cancer: Targeting ovarian cancer cells with the B7-H3-specific mAb 376.96. Gynecol Oncol (2014) 132:203–10. 10.1016/j.ygyno.2013.10.038 [] [[PubMed]
79. Kendsersky NM, Lindsay JM, Kolb EA, Smith MA, Teicher BA, Erickson S, 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), clincanres.4221.2020. 10.1158/1078-0432.CCR-20-4221 [] [[PubMed]
80. Scribner JA, Brown JG, Son T, Chiechi M, Li P, Sharma S, et al. . Preclinical Development of MGC018, a Duocarmycin-based Antibody–drug Conjugate Targeting B7-H3 for Solid Cancer. Mol Cancer Ther (2020) 19:2235–44. 10.1158/1535-7163.MCT-20-0116 [] [[PubMed]
81. Du H, Hirabayashi K, Ahn S, Kren NP, Montgomery SA, Wang X, 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) 35:221–37.e228. 10.1016/j.ccell.2019.01.002 ] [
82. Majzner RG, Theruvath JL, Nellan A, Heitzeneder S, Cui Y, Mount CW, 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. 10.1158/1078-0432.CCR-18-0432 [] [[PubMed]
83. Theruvath J, Sotillo E, Mount CW, Graef CM, Delaidelli A, Heitzeneder S, et al. . Locoregionally administered B7-H3-targeted CAR T cells for treatment of atypical teratoid/rhabdoid tumors. Nat Med (2020) 26:712–9. 10.1038/s41591-020-0821-8 ] [