Emerging combination immunotherapy strategies for breast cancer: dual immune checkpoint modulation, antibody-drug conjugates and bispecific antibodies.
Antibody–drug conjugates
Bispecific antibodies
Breast cancer
Immune checkpoint inhibitors
Nanoparticles
Journal
Breast cancer research and treatment
ISSN: 1573-7217
Titre abrégé: Breast Cancer Res Treat
Pays: Netherlands
ID NLM: 8111104
Informations de publication
Date de publication:
Jan 2022
Jan 2022
Historique:
received:
12
04
2021
accepted:
12
10
2021
pubmed:
31
10
2021
medline:
20
1
2022
entrez:
30
10
2021
Statut:
ppublish
Résumé
Breast cancer has historically been considered a non-immunogenic tumor. Multiple studies over the last 10-15 years have demonstrated that a small subset of breast cancers is immune-activated, with PD-L1 expression and/or TILs in the tumor microenvironment. The PD-1 inhibitor pembrolizumab in combination with chemotherapy is now approved by the US FDA for the first-line treatment of metastatic PD-L1 + triple negative breast cancer, and the PD-L1 inhibitor atezolizumab has also demonstrated clinical activity. The median progression-free survival for pembrolizumab or atezolizumab combined with chemotherapy increased with the addition of immunotherapy by 4.1 months and 2.5 months, respectively. Despite this success, there is major room for improvement. Clinical benefit is modest. Only about 40% of triple negative breast cancers are PD-L1 + , not all PD-L1 + patients with advanced triple negative breast cancer respond, and immunotherapy is not yet approved for advanced PD-L1-negative triple negative breast cancer, HER2 + breast cancer, or ER + breast cancer. It is likely that redundant pathways of immune suppression are active in breast cancer, or that important pathways of immune activation are silent. In this review, we discuss emerging strategies for targeting multiple pathways of immunoregulation in advanced breast cancer with dual immune checkpoint inhibition, bispecific antibodies, and novel antibody drug conjugates. We also discuss the potential of nanotechnology to improve the delivery of immunotherapeutics to the breast tumor microenvironment to enhance their antitumor activity.
Identifiants
pubmed: 34716871
doi: 10.1007/s10549-021-06423-0
pii: 10.1007/s10549-021-06423-0
doi:
Substances chimiques
Antibodies, Bispecific
0
B7-H1 Antigen
0
Immunoconjugates
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
291-302Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Chen DS, Mellman I (2013) Oncology meets immunology: the cancer-immunity cycle. Immunity 39(1):1–10. https://doi.org/10.1016/j.immuni.2013.07.012
doi: 10.1016/j.immuni.2013.07.012
pubmed: 23890059
Topper MJ, Vaz M, Marrone KA, Brahmer JA, Baylin SB (2020) The emerging role of epigenetic therapeutics in immuno-oncology. Nat Rev Clin Oncol 17(2):75–90. https://doi.org/10.1038/s41571-019-0266-5
doi: 10.1038/s41571-019-0266-5
pubmed: 31548600
Jenkins RW, Barbie DA, Flaherty KT (2018) Mechanisms of resistance to immune checkpoint inhibitors. Br J Cancer 118(1):9–16. https://doi.org/10.1038/bjc.2017.434
doi: 10.1038/bjc.2017.434
pubmed: 29319049
pmcid: 5765236
Emens LA (2018) Breast cancer immunotherapy: facts and hopes. Clin Cancer Res 24(3):511–520. https://doi.org/10.1158/1078-0432.CCR-16-3001
doi: 10.1158/1078-0432.CCR-16-3001
pubmed: 28801472
Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, Dieras V, Hegg R, Im S-A, Wright GS, Henschel V, Molinero L, Chui SY, Funke R, Husain A, Winer EP, Loi S, Emens LA, IMpassion130 Trial Investigators (2018) Atezolizumab and nab-paclitaxel in advanced triple negative breast cancer. N Engl J Med 379(22):2108–2121. https://doi.org/10.1056/NEJM0a1809615
doi: 10.1056/NEJM0a1809615
pubmed: 30345906
Cortes J, Cescon DW, Rugo HS, Nowecki Z, Im S-A, Yusof MM, Gallardo C, Lipatov O, Barrios CH, Holgado E, Iwata H, Masuda N, Otero MT, Gokmen E, Loi S, Guo Z, Zhao J, Aktan G, Karantza V, Schmid P, KEYNOTE-355 Investigators (2020) Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomized, placebo-controlled, double-blind, phase 3 clinical trial. Lancet 396(10265):1817–1828. https://doi.org/10.1016/S0140-6736(20)32531-9
doi: 10.1016/S0140-6736(20)32531-9
pubmed: 33278935
Rugo H, Cortes J, Cescon DW, Im, S-A, Usof MM, Gallardo C, Lipatov O, Barrios CH, Perez-Garcia J, Iwata H, Masuda N, Otero MT, Gokmen E, Loi S, Guo Z, Zhou X, Karantza V, Pan W, Schmid P (2021) KEYNOTE-355: Final results from a randomized, double-blind, phase 3 study of first-line pembrolizumab + chemotherapy vs placebo + chemotherapy for metastatic TNBC. ESMO Congress 2021, LBA16.
Emens LA, Ascierto PA, Darcy PK, Demaria S, Eggermont AMM, Redmond WL, Seliger B, Marincola FM (2017) Cancer immunotherapy: opportunities and challenges in the rapidly evolving clinical landscape. Eur J Cancer 81:116–129. https://doi.org/10.1016/j.ejca.2017.01.035
doi: 10.1016/j.ejca.2017.01.035
pubmed: 28623775
Vonderheide RH, Domchek SM, Clark AS (2017) Immunotherapy for breast cancer: what are we missing? Clin Cancer Res 23(11):2640–2646. https://doi.org/10.11158/1078-0432.CCR-16-2569
doi: 10.11158/1078-0432.CCR-16-2569
pubmed: 28572258
pmcid: 5480967
Goldberg J, Pastorello RG, Vallius T, Davis J, Cui YX, Agudo J, Waks AG, Keenan T, McAllister SS, Tolaney SM, Mittendorf EA (2021) Guerriero JL (2021) The immunology of hormone receptor positive breast cancer. Front Immunol 12:674192. https://doi.org/10.33389/fimmu.2021.674192.eCollection
doi: 10.33389/fimmu.2021.674192.eCollection
pubmed: 34135901
pmcid: 8202289
Wang H, Li S, Wang Q, Jin Z, Shao W, Gao Y, Li L, Lin K, Zhu L, Wang H, Liao X, Wang D (2021) Tumor immunological phenotype signature-based high-throughput screening for the discovery of combination immunotherapy compounds. Sci Adv. https://doi.org/10.1126/sciadv.abd7851
doi: 10.1126/sciadv.abd7851
pubmed: 34936460
pmcid: 8694617
Umansky V, Blattner C, Gebbardt C, Utikal J (2016) The role of myeloid-derived suppressor cells (MDSC) in cancer progression. Vaccines 4(4):36. https://doi.org/10.3390/vaccines4040036
doi: 10.3390/vaccines4040036
pmcid: 5192356
Markowitz J, Wesolowski R, Papenfuss T, Brooks TR, Carson WE (2013) Myeloid-derived suppressor cells in breast cancer. Breast Cancer Res Treat 140(1):13–21. https://doi.org/10.1007/s10549-013-2618-7
doi: 10.1007/s10549-013-2618-7
pubmed: 23828498
pmcid: 3773691
Watanabe MAE, Oda JMM, Amarante MK, Voltarelli JC (2010) Regulatory T cells and breast cancer: implications for immunopathogenesis. Cancer Metastasis Rev 29(4):569–579. https://doi.org/10.1007/s1055-010-9247-y
doi: 10.1007/s1055-010-9247-y
pubmed: 20830504
Gabrilovich DI, Ostrand-Rosenberg S, Bronte V (2012) Coordinated regulation of myeloid cells by tumours. Nature Rev Immunol 12(4):253–268. https://doi.org/10.1038/nri3175
doi: 10.1038/nri3175
Gatti-Mays ME, Balko J, Gameiro SR, Bear HD, Pabhakaran S, Fukui J, Disis ML, Nanda R, Gulley JL, Kalinsky K, Sater HA, Sparano JA, Cescon D, Page DB, McArthur H, Adams S, Mittendorf EA (2019) If we build it they will come: targeting the immune response to breast cancer. NPJ Breast Cancer. https://doi.org/10.1038/s41523/019/0133-7
doi: 10.1038/s41523/019/0133-7
pubmed: 31700993
pmcid: 6820540
Lao L, Fan S, Song E (2017) Tumor-associated macrophages as therapeutic targets for breast cancer. Advances in Experimental Medicine and Biology, vol 1026. Springer, New York LLC, pp 331–370
Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossman K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD (2015) Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373(1):23–34. https://doi.org/10.1056/NEJMoa1504030
doi: 10.1056/NEJMoa1504030
pubmed: 26027431
pmcid: 5698905
Santa-Maria CA, Kato T, Park JH, Kiyotani K, Rademaker A, Shah AN, Gross L, Blanco LZ, Jain S, Flaum L, Tellez C, Stein R, Uthe R, Gradishar WJ, Cristofanilli M, Nakamura Y, Giles FJ (2018) A pilot study of durvalumab and tremelimumab and immunogenomic dynamics in metastatic breast cancer. Oncotarget 9(27):18985–18996. https://doi.org/10.18632/oncotarget.24867
doi: 10.18632/oncotarget.24867
pubmed: 29721177
pmcid: 5922371
Christmas BJ, Rafie CI, Hopkins AC, Scott BA, Ma HS, Cruz KA, Woolman S, Armstrong TD, Connolly RM, Azad NA, Jaffee EM, Roussos Torres ET (2018) Entinostat converts immune-resistant breast and pancreatic cancers into checkpoint-responsive tumors by reprogramming tumor-infiltrating MDSCs. Cancer Immunol Res 6(12):1561–1577. https://doi.org/10.1158/2326-6066.CIR-18-0070
doi: 10.1158/2326-6066.CIR-18-0070
pubmed: 30341213
pmcid: 6279584
McCaw TR, Li M, Starenki D, Liu M, Cooper SJ, Arend RC, Forero A, Buchsbaum DJ, Randall TD (2019) Histone deacetylase inhibition promotes intratumoral CD8+ T cell responses, sensitizing murine breast tumors to anti-PD1. Cancer Immunol Immunother 68(12):2081–2094. https://doi.org/10.1007/s00262-019-02430-9
doi: 10.1007/s00262-019-02430-9
pubmed: 31720815
pmcid: 6879872
Wolchok J, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob JJ, Cowey CL, Lao CD, Wagstaff J, Schadendorf D, Ferrucci PF, Smylie M, Dummer R, Hill A, Hogg D, Haanen J, Carlino MS, Bechter O, Maio M, Marquez-Rodas I, Guidoboni M, McArthur G, Lebbe C, Ascierto PA, Long GV, Cebon J, Sosman J, Postow MA, Callahan MK, Walker D, Rollin L, Bhore R, Hodi FS, Larkin J (2017) Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med 377(14):1345–1356. https://doi.org/10.1056/NEJMoa1709684
doi: 10.1056/NEJMoa1709684
pubmed: 28889792
pmcid: 5706778
Desnoyers LR, Vasiljeva O, Richardson JH, Yang A, Menendez EE, Liang TW, Wong C, Bessette PH, Kamath K, Moore SJ, Sagert JG, Hostetter DR, Han F, Gee J, Flandez J, Markham K, Nguyen M, Krimm M, Wong KR, Liu S, Daugherty PS, West JW, Lowman HB (2013) Tumor-specific activation of an EGFR-targeting probody enhances therapeutic index. Sci Transl Med 5(207):207ra144. https://doi.org/10.1126/scitranslmed.3006682
doi: 10.1126/scitranslmed.3006682
pubmed: 24132639
Polu KR, Lowman HB (2014) Probody therapeutics for targeting antibodies to diseased tissue. Expert Opin Biol Ther 14(8):1049–1053. https://doi.org/10.1517/14712598.2014.920814
doi: 10.1517/14712598.2014.920814
pubmed: 24845630
Autio KA, Boni V, Humphrey RW, Naing A (2020) Probody therapeutics: an emerging class of therapies designed to enhance on-target effects with reduced off-tumor toxicity for us in immuno-oncology. Clin Cancer Res 26(5):984–989. https://doi.org/10.1158/1078-0432.CCR-19-1457
doi: 10.1158/1078-0432.CCR-19-1457
pubmed: 31601568
Rowland GF, O’Neill GJ, Davies DA (1975) Suppression of tumour growth in mice by a drug-antibody conjugate using a novel approach to linkage. Nature 255(5508):487–488
doi: 10.1038/255487a0
Moolten FL, Cooperband SR (1970) Selective destruction of target cells by diphtheria toxin conjugated to antibody directed against antigens on the cells. Science 169(3940):68–70. https://doi.org/10.1126/science.169.3940.68
doi: 10.1126/science.169.3940.68
pubmed: 4986716
Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Dieras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K, EMILIA Study Group (2013) Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 367(19):1783–1791. https://doi.org/10.1056/NEJMoa1209124
doi: 10.1056/NEJMoa1209124
Saini KS, Punie K, Twelves C, Bortini S, deAzambuja E, Anderson S, Criscitiello C, Awada A, Loi S (2021) Antibody-drug conjugates, immune checkpoint inhibitors, and their combination in breast cancer therapeutics. Expert Opin Biol Ther 21(7):945–962. https://doi.org/10.1080/1472598.2021.1936494
doi: 10.1080/1472598.2021.1936494
pubmed: 34043927
Barroso-Sousa R, Tolaney SM (2021) Clinical development of new antibody-drug conjugates in breast cancer: to infinity and beyond. BioDrugs 35(2):159–174. https://doi.org/10.1007/s40259-021-00472-z
doi: 10.1007/s40259-021-00472-z
pubmed: 33666903
Sau S, Petrovici A, Alsaab HO, Bhise K, Iyer AK (2019) PDL-1 antibody drug conjugate for selective chemo-guided immune modulation of cancer. Cancers (Basel) 11(2):232. https://doi.org/10.3390/cancers11020232
doi: 10.3390/cancers11020232
Scribner JA, Brown JB, Son T, Chiechi M, Li P, Sharma S, Li H, De Costa A, Li Y, Chen Y, Easton A, Yee-Toy NC, Chen FZ, Goriatov S, Barat B, Huang L, Wolff CR, Hooley J, Hotaling TE, Gaynutdinov T, Ciccarone V, Tamura J, Koenig S, Moore PA, Bonvini E, Loo D (2020) Preclinical development of MGC018, a duocarmycin-based antibody-drug conjugate targeting B7–H3 for solid cancer. Mol Cancer Ther. https://doi.org/10.1158/1535-7163.MCT-20-0116
doi: 10.1158/1535-7163.MCT-20-0116
pubmed: 32967924
Scribner JA, Chiechi M, Li P, Son T, Hooley J, Li Y, De Costa A, Lung P, Yee-Toy N, Chen F, Barat B, Wolff C, Ciccarone V, Tamura J, Koenig S, Bohac C, Wigginton J, Moore PA, Bonvini E, Loo D (2020) Abstract 5203: MGC018, a duocarmycin-based antibody-drug conjugate targeting B7–H3, exhibits immunomodulatory activity and enhanced antitumor activity in combination with checkpoint inhibitors. Cancer Res 80(16S):5203. https://doi.org/10.1158/1538-7445.am2020-5203
doi: 10.1158/1538-7445.am2020-5203
Bardia A, Mayer IA, Vahdat LT, Tolaney SM, Isakoff SJ, Diamond JR, O’Shaughnessy J, Moroose RL, Santin AD, Abramson VG, Shah NC, Rugo HS, Goldenberg DM, Sweidan AM, Iannone R, Washkowitz S, Sharkey RM, Wegener WA, Kalinsky K (2019) Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer. N Engl J Med 380(8):741–751. https://doi.org/10.1056/NEJMoa1814213
doi: 10.1056/NEJMoa1814213
pubmed: 30786188
Savas P, Salgado R, Denkert C, Sotiriou C, Darcy PK, Smyth MJ, Loi S (2016) Clinical relevance of host immunity in breast cancer: from TILs to the clinic. Nat Rev Clin Oncol 13(4):228–241. https://doi.org/10.1038/nrclinonc.2015.215
doi: 10.1038/nrclinonc.2015.215
pubmed: 26667975
Stagg J, Loi S, Divisekera U, Ngiow SF, Duret H, Yagita H, Teng MW, Smyth MJ (2011) Anti-ErbB-2 mAb therapy requires type I and II interferons and synergizes with anti-PD-1 or anti-CD137 mAb therapy. Proc Natl Acad Sci USA 108(17):7142–7247. https://doi.org/10.1073/pnas.1016569108
doi: 10.1073/pnas.1016569108
pubmed: 21482773
pmcid: 3084100
Akiyama K, Ebihara S, Yada A, Matsumura K, Aiba S, Nukiwa T, Takai T (2003) Targeting apoptotic tumor cells to Fc gamma R provides efficient and versatile vaccination against tumors by dendritic cells. J Immunol 170(4):1641–1648. https://doi.org/10.4049/jimmunol.170.4.1641
doi: 10.4049/jimmunol.170.4.1641
pubmed: 12574326
Varchetta S, Gibelli N, Olivero B, Nardini E, Gennari R, Gatti G, Silva LS, Villani L, Tagliabue E, Menard S, Costa A, Fagnoni FF (2007) Elements related to heterogeneity of antibody-dependent cell cytotoxicity in patients under trastuzumab therapy for primary operable breast cancer. Cancer Res 67(24):11991–11999. https://doi.org/10.1158/008-5472.CAN-07-2068
doi: 10.1158/008-5472.CAN-07-2068
pubmed: 18089830
Su S, Zhao J, Xing Y, Zhang X, Liu J, Ouyang Q, Chen J, Su F, Liu Q, Song E (2018) Immune checkpoint inhibition overcomes ADCP-induced immunosuppression by macrophages. Cell 175(2):442-457.e23. https://doi.org/10.1016/j.cell.2018.09.007
doi: 10.1016/j.cell.2018.09.007
pubmed: 30290143
Muller P, Kreuzaler M, Khan T, Thommen DS, Martin K, Glatz K, Savic S, Harbeck N, Nitz U, Gluz O, von Bergwelt-Baildon M, Kreipe H, Reddy S, Christgen M, Zippelius A (2015) Trastuzumab emtansine (T-DM1) renders HER2+ breast cancer highly susceptible to CTLA-4/PD-1 blockade. Sci Transl Med 7(315):315ra188. https://doi.org/10.1126/scitranslmed.aac4925
doi: 10.1126/scitranslmed.aac4925
pubmed: 26606967
Emens LA, Esteva FJ, Beresford M, Saura C, De Laurentiis M, Kim SB, Im S-A, Wang Y, Salgado R, Mani A, Shah J, Lambertini C, Liu H, de Haas SL, Patre M, Loi S (2020) Trastuzumab emtansine plus atezolizumab versus trastuzumab emtansine plus placebo in previously treated, HER2-positive advanced breast cancer (KATE2): a phase 2, multicentre, randomized, double-blind trial. Lancet Oncol 21(10):128301295. https://doi.org/10.1016/S1470-2045(20)304650-4
doi: 10.1016/S1470-2045(20)304650-4
Modi S, Saura C, Yamashita T, Park YH, Kim SB, Tamura K, Andre F, Iwata H, Ito Y, Tsurutani J, Sohn J, Denduluri N, Perrin C, Aogi K, Tokunaga E, Im SA, Lee KS, Hurvitz SA, Corest J, Lee C, Chen S, Zhang L, Shahidi J, Yver A, Krop I, DESTINY-Breast01 Investigators (2020) Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med 382(7):610–621. https://doi.org/10.1056/NEJMoa1914510
doi: 10.1056/NEJMoa1914510
pubmed: 31825192
Kohrt HE, Houot R, Weiskopf K, Goldstein MJ, Scheeren F, Czerwinski D, Colevas AD, Weng WK, Clarke MF, Carlson RW, Stockdale FE, Mollick JA, Chen L, Levy RJ (2012) Stimulation of natural killer cells with a CD137-specific antibody enhances trastuzumab efficacy in xenotransplant models of breast cancer. J Clin Invest 122(3):1066–1075. https://doi.org/10.1172/JCI61226
doi: 10.1172/JCI61226
pubmed: 22326955
pmcid: 3287235
Kohrt HE, Houot R, Weiskopf K, Goldstein MJ, Scheeren F, Czerwinski D, Colevas AD, Weng WK, Clarke MF, Carlson RW, Stockdale FE, Mollick JA, Chen L, Levy RJ (2019) Stimulation of natural killer cells with a CD137-specific antibody enhances trastuzumab efficacy in xenotransplant models of breast cancer. J Clin Invest 129(6):2595. https://doi.org/10.1172/JCI29688
doi: 10.1172/JCI29688
pubmed: 31157621
pmcid: 6546446
Yonezawa A, Dutt S, Chester C, Kim J, Kohrt HE (2015) Boosting cancer immunotherapy with anti-CD137 antibody therapy. Clin Cancer Res 21(14):3113–3120. https://doi.org/10.1158/1078-0432.CCR-15-0263
doi: 10.1158/1078-0432.CCR-15-0263
pubmed: 25908780
pmcid: 5422104
Corrales L, Matson V, Flood B, Spranger S, Gajewski TF (2017) Innate immune signaling and regulation in cancer immunotherapy. Cell Res 27(1):96–108. https://doi.org/10.1038/cr.2016.149
doi: 10.1038/cr.2016.149
pubmed: 27981969
Vanpouille-Box C, Hoffmann JA, Galluzzi L (2019) Pharmacologic modulation of nucleic acid sensors—therapeutic potential and persisting obstacles. Nat Rev Drug Discov 18(11):845–867. https://doi.org/10.1038/s41573-019-0043-2
doi: 10.1038/s41573-019-0043-2
pubmed: 31554927
Comeau MR, Brender T, Childs M, Brevik J, Winship D, Metz H, Chang J, Adamo J, Setter B, Xu H, Fan L-Q, Stevens B, Smith SW, Tan P, DuBose R, Latchman Y, Baum P, Odegard V (2020) Abstract 4537: SBT6050, a HER2-directed TLR8 ImmunoTAC
doi: 10.1158/1538-7445.AM2020-4537
Ackerman SE, Pearson CI, Gregorio JD, Gonzalez JC, Kenkel JA, Hartmann FJ, Luo A, Ho PY, LeBlanc H, Blum LK, Kimmey SC, Luo A, Nguyen ML, Paik JC, Sheu LY, Ackerman B, Lee A, Li H, Melrose J, Laura RP, Ramani VC, Henning KA, Jackson DY, Safina BS, Yonehiro G, Devens BH, Carmi Y, Chapin SJ, Bendall SC, Kowanetz M, Dornan D, Engleman EG, Alonso MN (2021) Immune-stimulating antibody conjugates elicit robust myeloid activation and durable antitumor immunity. Nat Cancer 2:18–33. https://doi.org/10.1038/s43018-020-00136-x
doi: 10.1038/s43018-020-00136-x
Labrijn AF, Janmaat ML, Reichert JM, Parren PWHI (2019) Bispecific antibodies: a mechanistic review of the pipeline. Nat Rev Drug Discov 18(8):585–608. https://doi.org/10.1038/s41573-019-0028-1
doi: 10.1038/s41573-019-0028-1
pubmed: 31175342
Przepiorka D, Ko CW, Deisseroth A, Yancey CL, Candau-Chacon R, Chiu HJ, Gehrke BJ, Gomez-Broughton C, Kane RC, Kirshner S, Mehrotra N, Ricks TK, Schmiel D, Song P, Zhao P, Zhou Q, Farrell AT, Pazdur R (2015) FDA approval: blinatumomab. Clin Cancer Res 21(18):4035–4039. https://doi.org/10.1158/1078-0432.CCR-15-0612
doi: 10.1158/1078-0432.CCR-15-0612
pubmed: 26374073
Kantarjian H, Stein A, Gokbuget N, Fielding AK, Schuh AC, Ribera JM, Wei A, Dombret H, Foa R, Bassan R, Arslan O, Sanz MA, Bergeron J, Demirkan F, Lech-Maranda E, Rambaldi A, Thomas X, Horst HA, Bukrggemann M, Klapper W, Wood BL, Fleishman A, Nagorsen D, Holland C, Zimmerman Z, Topp MS (2017) Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med 376(9):836–847. https://doi.org/10.1056/NEJMoa1609783
doi: 10.1056/NEJMoa1609783
pubmed: 28249141
pmcid: 5881572
Mittal D, Vijayan D, Neijssen J, Kreijtz J, Habraken MMJM, Van Eenennaam H, Van Elsas A, Smyth MJ (2019) Blockade of ErbB2 and PD-L1 using a bispecific antibody to improve targeted anti-ErbB2 therapy. Oncoimmunol 8(11):e1648171. https://doi.org/10.1080/2162402X.2019.1648171
doi: 10.1080/2162402X.2019.1648171
Ruiz IR, Vicario R, Morancho B, Morales CB, Arenas EJ, Herter S, Freimoser-Grundschober A, Somandin J, Sam J, Ast O, Barriocanal AM, Luque A, Escorihuela M, Varela I, Cuartas I, Nuciforo P, Fasani R, Peg V, Rubio I, Cortes J, Serra V, Escriva-de-Romani S, Sperinde J, Chenna A, Huang W, Winslow J, Albanell J, Seoane J, Scaltriti M, Baselga J, Tabernero J, Umana P, Bacac M, Saura C, Klein C, Arribas J (2018) p95HER2-T cell bispecific antibody for breast cancer treatment. Sci Transl Med. https://doi.org/10.1126/scitranslmed.aat1445
doi: 10.1126/scitranslmed.aat1445
pubmed: 29593104
pmcid: 6498439
Chang CH, Wang Y, Li R, Rossi DL, Liu D, Rossi EA, Cardillo TM, Goldenberg DM (2017) Combination therapy with bispecific antibodies and PD-1 blockade enhances the antitumor potency of T cells. Cancer Res 77(19):5384–5394. https://doi.org/10.1158/0008-5472.CAN-16-3431
doi: 10.1158/0008-5472.CAN-16-3431
pubmed: 28819027
Kamada H, Taki S, Nagano K, Inoue M, Ando D, Mukai Y, Higashisaka K, Yoshioka Y, Tsutsumi Y, Tshunoda S (2015) Generation and characterization of a bispecific diabody targeting both EPH receptor A10 and CD3. Biochem Biophys Res Commun 456(4):908–912. https://doi.org/10.1016/j.bbrc.2014.12.030
doi: 10.1016/j.bbrc.2014.12.030
pubmed: 25528586
Fisher TS, Hooper AT, Lucas J, Clark TH, Rohner AK, Peano B, Elliott MW, Tsaparikos K, Wang H, Golas J, Gavriil M, Haddish-Berhane N, Tchistiakova L, Gerber H-P, Root AR, May C (2018) A CD3-bispecific molecule targeting P-cadherin demonstrates T cell-mediated regression of established tumors in mice. Cancer Immunol Immunother 67(2):247–259. https://doi.org/10.1007/s00262-017-2081-0
doi: 10.1007/s00262-017-2081-0
pubmed: 29067496
Kubo M, Umebayashi M, Kurata K, Mori H, Kai M, Onishi H, Katao M, Nakamura M, Morisaki T (2018) Catumaxomab with activated T-cells efficiently lyses chemoresistant EpCAM-positive triple-negative breast cancer cell lines. Anticancer Res 38(7):4273–4279. https://doi.org/10.21873/anticanres.12724
doi: 10.21873/anticanres.12724
pubmed: 29970561
Del Bano J, Flores-Flores R, Josselin E, Goubard A, Ganier L, Castellano R, Chames P, Baty D, Kerfelec B (2019) A bispecific antibody-based approach for targeting mesothelin in triple negative breast cancer. Front Immunol 10:1593. https://doi.org/10.3389/fimmu.2019.01593
doi: 10.3389/fimmu.2019.01593
pubmed: 31354732
pmcid: 6636429
Berezhnoy A, Sumrow BJ, Stahl K, Shah K, Liu D, Li J, Hao S-S, De Costa A, Kaul S, Bendell J, Cote GM, Luke JJ, Sanborn RE, Sharma MR, Chen F, Li H, Diedrich G, Bonvini E, Moore PA (2020) Development and preliminary clinical activity of PD-1-guided CTLA-4 blocking bispecific DART molecule. Cell Rep Med 1(9):100163. https://doi.org/10.1016/j.xcrm.2020.100163
doi: 10.1016/j.xcrm.2020.100163
pubmed: 33377134
pmcid: 7762776
La Motte-Mohs R, Shah K, Brown JG, Smith D, Gorlatov S, Ciccarone V, Tamura JK, Li H, Rillema JR, Licea M, Shoemaker C, He L, Vasanwala F, Hill J, Whiddon A, Pascuccio M, Saini S, Chen FZ, De Costa A, Easton A, Lung P, Li J, Stahl K, Nordstrom J, Koenig S, Bonvini E, Johnshon S, Moore PA. (2017) Abstract Preclinical characterization of MGD013, a PD-1 x LAG-3 Bispecific DART molecule. Presented at the Society for Immunotherapy of Cancer 32nd Annual Meeting, November 8–12, 2017, National Harbor, MD.
Patel M, Luke J, Hamilton E, Chmielowski B, Blumenschein G, Kindler H, Bahadur S, Santa-Maria C, Koucheki J, Sun J, Kaul S, Chen F, Zhang X, Muth J, Kaminker P, Moore P, Sumrow B, Ulahannan S (2020) Abstract 313: A phase 1 evaluation of tebotelimab, a bispecific PD-1 x LAG-3 DART molecule, in combination with margetuximab in patients with advanced HER2+ neoplasms. J Immunother Cancer. https://doi.org/10.1136/jitc-2020-SITC2020.0313
doi: 10.1136/jitc-2020-SITC2020.0313
pubmed: 33219092
pmcid: 7682456
Strauss J, Heery CR, Schlom J, Madan RA, Cao L, Kang Z, Lamping E, Marte JL, Donahue RN, Grenga I, Cordes L, Christensen O, Mahnke L, Helwig C, Gulley JL (2018) Phase 1 trial of M7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGFbeta in advanced solid tumors. Clin Cancer Res 24(6):1287–1295. https://doi.org/10.1158/1078-0432.CCR-17-2653
doi: 10.1158/1078-0432.CCR-17-2653
pubmed: 29298798
pmcid: 7985967
Strauss J, Gatti-Mays ME, Cho BC, Hill A, Salas S, McClay E, Redman JM, Sater HA, Donahue RN, Jochems C, Lamping E, Burmeister A, Marte JL, Cordes LM, Bilusic M, Karzai F, Ojalvo LS, Jehl G, Rolfe PA, Hinrichs CS, Madan RA, Schlom J, Gulley JL (2020) Abstract 1395: Bintrafusp alpha, a bifunctional fusion protein targeting TGF-beta and PD-L1, in patients with human papillomavirus malignancies. J Immunother Cancer 8:e001395. https://doi.org/10.1136/jitc-2020-001395
doi: 10.1136/jitc-2020-001395
pubmed: 33323462
pmcid: 7745517
Bahreyni A, Mohamud Y, Luo H (2020) Emerging nanomedicines for effective breast cancer immunotherapy. J Nanobiotechnol 18(1):180. https://doi.org/10.1186/s12951-020-00741-z
doi: 10.1186/s12951-020-00741-z
Shao K, Singha S, Clemente-Casares X, Tsai S, Yang Y, Santamaria P (2015) Nanoparticle-based immunotherapy of cancer. ACS Nano 9(1):16–30. https://doi.org/10.1021/nn5062029
doi: 10.1021/nn5062029
pubmed: 25469470
Ramesh A, Brouillard A, Kumar S, Nandi D, Kulkarni A (2020) Dual inhibition of CSF1R and MAPK pathways using supramoleculuar nanoparticles enhances macrophage immunotherapy. Biomaterials 227:119559. https://doi.org/10.1016/j.biomaterials.2019.119559
doi: 10.1016/j.biomaterials.2019.119559
pubmed: 31670078
Buss CG, Bhatia SN (2020) Nanoparticle delivery of immunostimulatory oligonucleotides enhances response to checkpoint inhibitor therapeutics. Proc Natl Acad Sci USA 177(24):13428–13436. https://doi.org/10.1073/pnas.2001569117
doi: 10.1073/pnas.2001569117