Wykes MN, Lewin SR. Immune checkpoint blockade in infectious diseases. Nat Rev Immunol. 2018;18:91–104. https://doi.org/10.1038/nri.2017.112.

Article  CAS  PubMed  Google Scholar 

Powles T, Plimack ER, Soulières D, Waddell T, Stus V, Gafanov R, et al. Pembrolizumab plus Axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial. Lancet Oncol. 2020;21:1563–73. https://doi.org/10.1016/s1470-2045(20)30436-8.

Article  CAS  PubMed  Google Scholar 

Adams S, Loi S, Toppmeyer D, Cescon DW, De Laurentiis M, Nanda R, et al. Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study. Ann Oncol. 2019;30:405–11. https://doi.org/10.1093/annonc/mdy518.

Article  CAS  PubMed  Google Scholar 

Vafaei S, Zekiy AO, Khanamir RA, Zaman BA, Ghayourvahdat A, Azimizonuzi H, et al. Combination therapy with immune checkpoint inhibitors (ICIs); a new frontier. Cancer Cell Int. 2022;22:2. https://doi.org/10.1186/s12935-021-02407-8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Koyama S, Akbay EA, Li YY, Herter-Sprie GS, Buczkowski KA, Richards WG, et al. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun. 2016;7:10501. https://doi.org/10.1038/ncomms10501.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Curran MA, Montalvo W, Yagita H, Allison JP. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci U S A. 2010;107:4275–80. https://doi.org/10.1073/pnas.0915174107.

Article  PubMed  PubMed Central  Google Scholar 

Gao J, Ward JF, Pettaway CA, Shi LZ, Subudhi SK, Vence LM, et al. VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer. Nat Med. 2017;23:551–5. https://doi.org/10.1038/nm.4308.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD, et al. Five-year survival with combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med. 2019;381:1535–46. https://doi.org/10.1056/NEJMoa1910836.

Article  CAS  PubMed  Google Scholar 

Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined Nivolumab and Ipilimumab or Monotherapy in untreated melanoma. N Engl J Med. 2015;373:23–34. https://doi.org/10.1056/NEJMoa1504030.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Boutros C, Tarhini A, Routier E, Lambotte O, Ladurie FL, Carbonnel F, et al. Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. Nat Reviews Clin Oncol. 2016;13:473–86. https://doi.org/10.1038/nrclinonc.2016.58.

Article  CAS  Google Scholar 

Wolchok JD, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob J-J, Cowey CL, et al. Overall survival with combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med. 2017;377:1345–56. https://doi.org/10.1056/NEJMoa1709684.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dahlén E, Veitonmäki N, Norlén P. Bispecific antibodies in cancer immunotherapy. Therapeutic Adv Vaccines Immunotherapy. 2018;6:3–17. https://doi.org/10.1177/2515135518763280.

Article  CAS  Google Scholar 

Kim KM, Kim HW, Kim JO, Baek KM, Kim JG, Kang CY. Induction of 4-1BB (CD137) expression by DNA damaging agents in human T lymphocytes. Immunology. 2002;107:472–9. https://doi.org/10.1046/j.1365-2567.2002.01538.x.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sanchez-Paulete AR, Labiano S, Rodriguez-Ruiz ME, Azpilikueta A, Etxeberria I, Bolaños E, et al. Deciphering CD137 (4-1BB) signaling in T-cell costimulation for translation into successful cancer immunotherapy. Eur J Immunol. 2016;46:513–22. https://doi.org/10.1002/eji.201445388.

Article  CAS  PubMed  Google Scholar 

Sabbagh L, Pulle G, Liu Y, Tsitsikov EN, Watts TH. ERK-Dependent Bim Modulation downstream of the 4-1BB-TRAF1 Signaling Axis is a critical mediator of CD8 T cell survival in Vivo1. J Immunol. 2008;180:8093–101. https://doi.org/10.4049/jimmunol.180.12.8093.

Article  CAS  PubMed  Google Scholar 

Melero I, Shuford WW, Newby SA, Aruffo A, Ledbetter JA, Hellström KE, et al. Monoclonal antibodies against the 4-1BB T-cell activation molecule eradicate established tumors. Nat Med. 1997;3:682–5. https://doi.org/10.1038/nm0697-682.

Article  CAS  PubMed  Google Scholar 

Gauttier V, Judor JP, Le Guen V, Cany J, Ferry N, Conchon S. Agonistic anti-CD137 antibody treatment leads to antitumor response in mice with liver cancer. Int J Cancer. 2014;135:2857–67. https://doi.org/10.1002/ijc.28943.

Article  CAS  PubMed  Google Scholar 

Segal NH, He AR, Doi T, Levy R, Bhatia S, Pishvaian MJ, et al. Phase I study of single-Agent Utomilumab (PF-05082566), a 4-1BB/CD137 agonist, in patients with Advanced Cancer. Clin Cancer Res. 2018;24:1816–23. https://doi.org/10.1158/1078-0432.Ccr-17-1922.

Article  CAS  PubMed  Google Scholar 

Segal NH, Logan TF, Hodi FS, McDermott D, Melero I, Hamid O, et al. Results from an Integrated Safety Analysis of Urelumab, an agonist Anti-CD137 monoclonal antibody. Clin Cancer Res. 2017;23:1929–36. https://doi.org/10.1158/1078-0432.Ccr-16-1272.

Article  CAS  PubMed  Google Scholar 

You G, Lee Y, Kang YW, Park HW, Park K, Kim H, et al. B7-H3×4-1BB bispecific antibody augments antitumor immunity by enhancing terminally differentiated CD8(+) tumor-infiltrating lymphocytes. Sci Adv. 2021;7. https://doi.org/10.1126/sciadv.aax3160.

Song MY, Lee E-J, Chung H, Lee Y, Park YB, Jee MH, et al. Abstract 6524: a novel HER2/4-1BB bispecific antibody, YH32367 (ABL105) shows potent anti-tumor effect through tumor-directed T cell activation. Cancer Res. 2020;80:6524. https://doi.org/10.1158/1538-7445.Am2020-6524.

Article  Google Scholar 

Qu QX, Zhu XY, Du WW, Wang HB, Shen Y, Zhu YB, et al. 4-1BB Agonism Combined with PD-L1 Blockade increases the number of tissue-resident CD8 + T cells and facilitates Tumor Abrogation. Front Immunol. 2020;11:577. https://doi.org/10.3389/fimmu.2020.00577.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wang Y, Zhang X, Xu C, Nan Y, Fan J, Zeng X, et al. Targeting 4-1BB and PD-L1 induces potent and durable antitumor immunity in B-cell lymphoma. Front Immunol. 2022;13:1004475. https://doi.org/10.3389/fimmu.2022.1004475.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yuwen H, Li T, Ren Y, Hoenemann D, Mei J, Shan B, et al. 893 ATG-101, a novel PD-L1/4–1BB bispecific antibody, augments anti-tumor immunity through immune checkpoint inhibition and PDL1-directed 4–1BB activation. J Immunother Cancer. 2021;9:A936–7. https://doi.org/10.1136/jitc-2021-SITC2021.893.

Article  Google Scholar 

Burvenich IJG, Goh YW, Guo N, Gan HK, Rigopoulos A, Cao D, et al. Radiolabelling and preclinical characterization of (89)Zr-Df-radiolabelled bispecific anti-PD-L1/TGF-βRII fusion protein bintrafusp alfa. Eur J Nucl Med Mol Imaging. 2021;48:3075–88. https://doi.org/10.1007/s00259-021-05251-0.

Article  CAS  PubMed  Google Scholar 

Wichmann CW, Poniger S, Guo N, Roselt P, Rudd SE, Donnelly PS, et al. Automated radiosynthesis of [89Zr]Zr-DFOSq-Durvalumab for imaging of PD-L1 expressing tumours in vivo. Nucl Med Biol. 2023;120–121:108351. https://doi.org/10.1016/j.nucmedbio.2023.108351.

Article  CAS  PubMed  Google Scholar 

Parakh S, Lee ST, Gan HK, Scott AM. Radiolabeled antibodies for Cancer Imaging and Therapy. Cancers. 2022;14:1454.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bensch F, van der Veen EL, Lub-de Hooge MN, Jorritsma-Smit A, Boellaard R, Kok IC, et al. 89Zr-atezolizumab imaging as a non-invasive approach to assess clinical response to PD-L1 blockade in cancer. Nat Med. 2018;24:1852–8. https://doi.org/10.1038/s41591-018-0255-8.

Article  CAS  PubMed  Google Scholar 

Lindmo T, Boven E, Cuttitta F, Fedorko J, Bunn PA Jr. Determination of the immunoreactive fraction of radiolabeled monoclonal antibodies by linear extrapolation to binding at infinite antigen excess. J Immunol Methods. 1984;72:77–89. https://doi.org/10.1016/0022-1759(84)90435-6.

Article  CAS  PubMed  Google Scholar 

Zheng Y, Fang YC, Li J. PD-L1 expression levels on tumor cells affect their immunosuppressive activity. Oncol Lett. 2019;18:5399–407. https://doi.org/10.3892/ol.2019.10903.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lin G, Fan X, Zhu W, Huang C, Zhuang W, Xu H, et al. Prognostic significance of PD-L1 expression and tumor infiltrating lymphocyte in surgically resectable non-small cell lung cancer. Oncotarget. 2017;8:83986–94. https://doi.org/10.18632/oncotarget.20233.

Article  PubMed  PubMed Central  Google Scholar 

Darga EP, Dolce EM, Fang F, Kidwell KM, Gersch CL, Kregel S, et al. PD-L1 expression on circulating tumor cells and platelets in patients with metastatic breast cancer. PLoS ONE. 2021;16:e0260124. https://doi.org/10.1371/journal.pone.0260124.

Article  CAS  PubMed  PubMed Central