Immune checkpoint antibody drugs have opened up a new era in the field of tumor treatment since the 20th century. In 2021, the global market share of antitumor monoclonal antibody drugs has reached 62 billion US dollars. In recent years, domestic enterprises have also accelerated their development in this field. However, a big gap still exists between these enterprises and international pharmaceutical giants. In this context, it is of vital significance to fully grasp the international research and development trends and the panorama of the R&D pipeline. The research topics of core articles in this research field in the past 10 years were analyzed, and the development trend of the field was revealed through the evolution of the research topics. Seven active research directions were identified. In-depth analysis of specific research directions was carried out through further data mining from professional databases and institutional websites. Comprehensive analysis indicated that three directions including the efficacy and safety surveillance of marketed antibody drugs and drug combination, new antibody drugs such as bispecific antibodies and antibody-drug conjugates, and new targets represented by 4-1BB have been the research hotspots and focuses in recent years. Adverse event monitoring of marketed drugs should be strengthened, and efforts should be stepped up to support the research and development of new antibody drugs.
[1] Mullard A. FDA approves 100th monoclonal antibody product[J]. Nature Reviews Drug Discovery, 2021, 20(7): 491-495.
[2] Chen C M, Dubin R, Kim M C. Emerging trends and new developments in regenerative medicine: A scientometric update (2000—2014) [J]. Expert Opinion on Biological Therapy, 2014, 14(9): 1295-1317.
[3] Ribas A, Wolchok J D. Cancer immunotherapy using checkpoint blockade[J]. Science, 2018, 359(6382): 1350-1355.
[4] Morad G, Helmink B A, Sharma P, et al. Hallmarks of response, resistance, and toxicity to immune checkpoint blockade[J]. Cell, 2021, 184(21): 5309-5337.
[5] Rittmeyer A, Barlesi F, Waterkamp D, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): A phase 3, open-label, multicentre randomised controlled trial [J]. The Lancet, 2017, 389(10066): 255-265.
[6] Gandhi L, Rodíguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung Cancer[J]. The New England Journal of Medicine, 2018, 378(22): 2078-2092.
[7] Brahmer J, Reckamp K L, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer[J]. The New England Journal of Medicine, 2015, 373(2): 123-135.
[8] Beck A, Goetsch L, Dumontet C, et al. Strategies and challenges for the next generation of antibody–drug conjugates[J]. Nature Reviews Drug Discovery, 2017, 16(5): 315-337.
[9] Drago J Z, Modi S, Chandarlapaty S. Unlocking the potential of antibody-drug conjugates for cancer therapy[J]. Nature Reviews Clinical Oncology, 2021, 18(6): 327-344.
[10] von Minckwitz G, Huang C S, Mano M S, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer[J]. The New England Journal of Medicine, 2019, 380(7): 617-628.
[11] Modi S, Saura C, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer[J]. The New England Journal of Medicine, 2020, 382(7): 610-621.
[12] Fu Z W, Li S J, Han S F, et al. Antibody drug conjugate: The "biological missile" for targeted cancer therapy[J]. Signal Transduction and Targeted Therapy, 2022, 7(1):93
[13] Labrijn A F, Janmaat M L, Reichert J M, et al. Bispecific antibodies: A mechanistic review of the pipeline[J]. Nature Reviews Drug Discovery, 2019, 18(8): 585-608.
[14] Si Lim S J, Grupp S A, Dinofia A M. Tisagenlecleucel for treatment of children and young adults with relapsed/refractory B-cell acute lymphoblastic leukemia[J]. Pediatric Blood & Cancer, 2021, 68(9): e29123.
[15] Esfandiari A, Cassidy S, Webster R M. Bispecific antibodies in oncology[J]. Nature Reviews Drug Discovery, 2022, 21(6): 411-412.
[16] Maakaron J E, Hu M, El Juridi N. Chimeric antigen receptor T cell therapy for cancer: Clinical applications and practical considerations[J]. British Medical Journal, 2022, 378: e068956.
[17] Chester C, Sanmamed M F, Wang J, et al. Immunotherapy targeting 4-1BB: Mechanistic rationale, clinical results, and future strategies[J]. Blood, 2018, 131(1): 49-57.
[18] Hinner M J, Aiba R S B, Jaquin T J, et al. Tumor-localized costimulatory T-cell engagement by the 4-1BB/ HER2 bispecific antibody-anticalin fusion PRS-343[J].Clinical Cancer Research, 2019, 25(19): 5878-5889.
[19] Claus C, Ferrara C, Xu W, et al. Tumor-targeted 4-1BB agonists for combination with T cell bispecific antibodies as off-the-shelf therapy[J]. Science Translational Medicine, 2019, 11(496): eaav5989.
[20] Lakins M A, Koers A, Giambalvo R, et al. FS222, a CD137/PD-L1 Tetravalent bispecific antibody, exhibits low toxicity and antitumor activity in colorectal cancer models[J]. Clinical Cancer Research, 2020, 26(15): 4154-4167.
[21] Wang Y T, Ji W D, Jiao H M, et al. Targeting 4-1BB for tumor immunotherapy from bench to bedside[J]. Frontiers in Immunology, 2022, 13: 975926.
[22] Kim A M J, Nemeth M R, Lim S O. 4-1BB: A promising target for cancer immunotherapy [J]. Frontiers in Oncology, 2022, 12: 968360.
[23] Overman M J, Mcdermott R, Leach J L, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): An open-label, multicentre, phase 2 study[J]. The Lancet Oncology, 2017, 18(9): 1182-1191.
[24] Andre T, Shiu K K, Kim T W, et al. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer[J]. New England Journal of Medicine, 2020, 383(23): 2207-2218.
[25] Weng J, Li S, Zhu Z, et al. Exploring immunotherapy in colorectal cancer[J]. Journal of Hematology & Oncology, 2022, 15(1):1-28.
[26] Ramos-Casals M, Brahmer J R, Callahan M K, et al. Immune-related adverse events of checkpoint inhibitors[J]. Nature Reviews Disease Primers, 2020, 6(1): 38.