Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541:321–30.

Article  CAS  PubMed  Google Scholar 

Seto T, Sam D, Pan M. Mechanisms of primary and secondary resistance to immune checkpoint inhibitors in cancer. Med Sci (Basel). 2019;7:14.

CAS  PubMed  Google Scholar 

Marei HE, Hasan A, Pozzoli G, Cenciarelli C. Cancer immunotherapy with immune checkpoint inhibitors (ICIs): potential, mechanisms of resistance, and strategies for reinvigorating T cell responsiveness when resistance is acquired. Cancer Cell Int. 2023;23:64.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027–34.

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Diskin B, Adam S, Cassini MF, Sanchez G, Liria M, Aykut B, et al. PD-L1 engagement on T cells promotes self-tolerance and suppression of neighboring macrophages and effector T cells in cancer. Nat Immunol. 2020;21:442–54.

Article  CAS  PubMed  Google Scholar 

Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443–54.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cercek A, Lumish M, Sinopoli J, Weiss J, Shia J, Lamendola-Essel M, et al. PD-1 blockade in mismatch repair-deficient, locally advanced rectal cancer. N Engl J Med. 2022;386:2363–76.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brahmer JR, Tykodi SS, Chow LQM, Hwu W-J, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366:2455–65.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–23.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, et al. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2023;41:943–54.

Article  CAS  PubMed  Google Scholar 

Shin DS, Zaretsky JM, Escuin-Ordinas H, et al. Primary resistance to PD-1 blockade mediated by JAK1/2 mutations. Cancer Discov. 2017;7(2):188–201.

Article  CAS  PubMed  Google Scholar 

Anagnostou V, Smith KN, Forde PM, Niknafs N, Bhattacharya R, White J, et al. Evolution of neoantigen landscape during immune checkpoint blockade in non-small cell lung cancer. Cancer Discov. 2017;7:264–76.

Article  CAS  PubMed  Google Scholar 

Sade-Feldman M, Jiao YJ, Chen JH, Rooney MS, Barzily-Rokni M, Eliane J-P, et al. Resistance to checkpoint blockade therapy through inactivation of antigen presentation. Nat Commun. 2017;8:1136.

Article  PubMed  PubMed Central  Google Scholar 

O’Malley DM, Neffa M, Monk BJ, Melkadze T, Huang M, Kryzhanivska A, et al. Dual PD-1 and CTLA-4 checkpoint blockade using balstilimab and zalifrelimab combination as second-line treatment for advanced cervical cancer: an open-label Phase II study. J Clin Oncol. 2022;40:762–71.

Article  PubMed  Google Scholar 

Liu L, Huang X, Shi F, Song J, Guo C, Yang J, et al. Combination therapy for pancreatic cancer: anti-PD-(L)1-based strategy. J Exp Clin Cancer Res. 2022;41:56.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhu W-Y, Jin X-Y. A narrative review of combination therapy of PD-1/PD-L1 blockade with standard approaches for the treatment of breast cancer: clinical application and immune mechanism. Ann Palliat Med. 2021;10:10075–82.

Article  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.

Article  PubMed  PubMed Central  Google Scholar 

Yi M, Zheng X, Niu M, Zhu S, Ge H, Wu K. Combination strategies with PD-1/PD-L1 blockade: current advances and future directions. Mol Cancer. 2022;21:28.

Article  PubMed  PubMed Central  Google Scholar 

Cheng W, Kang K, Zhao A, Wu Y. Dual blockade immunotherapy targeting PD-1/PD-L1 and CTLA-4 in lung cancer. J Hematol Oncol. 2024;17:54.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jiang C, Zhang L, Xu X, Qi M, Zhang J, He S, et al. Engineering a smart agent for enhanced immunotherapy effect by simultaneously blocking PD-L1 and CTLA-4. Adv Sci (Weinh). 2021;8: e2102500.

Article  PubMed  Google Scholar 

Zhou Y, Penny HL, Kroenke MA, Bautista B, Hainline K, Chea LS, et al. Immunogenicity assessment of bispecific antibody-based immunotherapy in oncology. J Immunother Cancer. 2022;10: e004225.

Article  PubMed  PubMed Central  Google Scholar 

Li T, Niu M, Zhou J, Wu K, Yi M. The enhanced antitumor activity of bispecific antibody targeting PD-1/PD-L1 signaling. Cell Commun Signal. 2024;22:179.

Article  PubMed  PubMed Central  Google Scholar 

Kraman M, Faroudi M, Allen NL, Kmiecik K, Gliddon D, Seal C, et al. FS118, a bispecific antibody targeting LAG-3 and PD-L1, enhances T-cell activation resulting in potent antitumor activity. Clin Cancer Res. 2020;26:3333–44.

Article  CAS  PubMed  Google Scholar 

Nisonoff A, Wissler FC, Lipman LN. Properties of the major component of a peptic digest of rabbit antibody. Science. 1960;132:1770–1.

Article  CAS  PubMed  Google Scholar 

Nisonoff A, Rivers MM. Recombination of a mixture of univalent antibody fragments of different specificity. Arch Biochem Biophys. 1961;93:460–2.

Article  CAS  PubMed  Google Scholar 

Milstein C, Cuello AC. Hybrid hybridomas and their use in immunohistochemistry. Nature. 1983;305:537–40.

Article  CAS  PubMed  Google Scholar 

Merchant AM, Zhu Z, Yuan JQ, Goddard A, Adams CW, Presta LG, et al. An efficient route to human bispecific IgG. Nat Biotechnol. 1998;16:677–81.

Article  CAS  PubMed  Google Scholar 

Somasundaram, et al. Development of a trispecific antibody conjugate that directs two distinct tumor-associated antigens to CD64 on myeloid effector cells. Hum Antibodies. 1999;9:47–54.

Article  CAS  PubMed  Google Scholar 

Trispecifics improve immune-cell engagement. Cancer Discov. 2022;12(6):1404.

Runcie K, Budman DR, John V, Seetharamu N. Bi-specific and tri-specific antibodies—the next big thing in solid tumor therapeutics. Mol Med. 2018;24(1):50.

Article  PubMed  PubMed Central