A novel anti-HER2 anthracycline-based antibody-drug conjugate induces adaptive anti-tumor immunity and potentiates PD-1 blockade in breast cancer

Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235:177–82.

Dawood S, Broglio K, Buzdar AU, Hortobagyi GN, Giordano SH. Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol Proc Am Soc Clin Oncol. 2010;28:92–8.

Hudis CA. Trastuzumab--mechanism of action and use in clinical practice. N Engl J Med. 2007;357:39–51.

Lewis Phillips GD, Li G, Dugger DL, Crocker LM, Parsons KL, Mai E, et al. Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res. American Association for Cancer Research. 2008;68:9280–90.

Krop IE, Kim S-B, González-Martín A, LoRusso PM, Ferrero J-M, Smitt M, et al. Trastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15:689–99.

Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med Massachusetts Medical Society. 2012;367:1783–91.

Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A. Primary, adaptive, and acquired resistance to Cancer immunotherapy. Cell. 2017;168:707–23.

Gerber H-P, Sapra P, Loganzo F, May C. Combining antibody-drug conjugates and immune-mediated cancer therapy: what to expect? Biochem Pharmacol. 2016;102:1–6.

Müller P, Kreuzaler M, Khan T, Thommen DS, Martin K, Glatz K, et al. Trastuzumab emtansine (T-DM1) renders HER2+ breast cancer highly susceptible to CTLA-4/PD-1 blockade. Sci Transl Med. American Association for the Advancement of Science; 2015;7:315ra188–8.

Polakis P. Antibody Drug Conjugates for Cancer Therapy. Esbenshade TA, editor. Pharmacol Rev American Society for Pharmacology and Experimental Therapeutics; 2016;68:3–19.

Beerli RR, Hell T, Merkel AS, Grawunder U. Sortase Enzyme-Mediated Generation of Site-Specifically Conjugated Antibody Drug Conjugates with High In Vitro and In Vivo Potency. Hagemeyer CE, editor. PLoS ONE. 2015;10:e0131177.

Stefan N, Gébleux R, Waldmeier L, Hell T, Escher M, Wolter FI, et al. Highly Potent, Anthracycline-based Antibody-Drug Conjugates Generated by Enzymatic, Site-specific Conjugation. Mol Cancer Ther American Association for Cancer Research. 2017;16:879–92.

Yu S-F, Zheng B, Go M, Lau J, Spencer S, Raab H, et al. A Novel Anti-CD22 Anthracycline-Based Antibody-Drug Conjugate (ADC) That Overcomes Resistance to Auristatin-Based ADCs. Clin Cancer Res American Association for Cancer Research. 2015;21:3298–306.

Junttila MR, Mao W, Wang X, Wang B-E, Pham T, Flygare J, et al. Targeting LGR5+ cells with an antibody-drug conjugate for the treatment of colon cancer. Sci Transl Med American Association for the Advancement of Science; 2015;7:314ra186–6.

Orsini F, Pavelic Z, Mihich E. Increased primary cell-mediated immunity in culture subsequent to adriamycin or daunorubicin treatment of spleen donor mice. Cancer Res. 1977;37:1719–26.

Mattarollo SR, Loi S, Duret H, Ma Y, Zitvogel L, Smyth MJ. Pivotal role of innate and adaptive immunity in anthracycline chemotherapy of established tumors. Cancer Res American Association for Cancer Research. 2011;71:4809–20.

Bloy N, Garcia P, Laumont CM, Pitt JM, Sistigu A, Stoll G, et al. Immunogenic stress and death of cancer cells: contribution of antigenicity vs adjuvanticity to immunosurveillance. Immunol Rev. 2017;280:165–74.

Galluzzi L, Bravo-San Pedro JM, Demaria S, Formenti SC, Kroemer G. Activating autophagy to potentiate immunogenic chemotherapy and radiation therapy. Nat Rev Clin Oncol. 2017;14:247–58.

Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. Annu Rev Immunol Annual Reviews. 2013;31:51–72.

Krysko DV, Garg AD, Kaczmarek A, Krysko O, Agostinis P, Vandenabeele P. Immunogenic cell death and DAMPs in cancer therapy. Nat Rev Cancer Nature Publishing Group. 2012;12:860–75.

Martin K, Müller P, Schreiner J, Prince SS, Lardinois D, Heinzelmann-Schwarz VA, et al. The microtubule-depolymerizing agent ansamitocin P3 programs dendritic cells toward enhanced anti-tumor immunity. Cancer Immunol Immunother. Springer Berlin Heidelberg. 2014;63:925–38.

Müller P, Martin K, Theurich S, Schreiner J, Savic S, Terszowski G, et al. Microtubule-depolymerizing agents used in antibody-drug conjugates induce antitumor immunity by stimulation of dendritic cells. Cancer Immunol Res. 2014;2:741–55.

Waldmeier L, Hellmann I, Gutknecht CK, Wolter FI, Cook SC, Reddy ST, et al. Transpo-mAb display: Transposition-mediated B cell display and functional screening of full-length IgG antibody libraries. mAbs. Taylor & Francis. 2016;8:726–40.

Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. BioMed Central. 2014;15:550.

Huber W, Carey VJ, Gentleman R, Anders S, Carlson M, Carvalho BS, et al. Orchestrating high-throughput genomic analysis with Bioconductor. Nature Methods Nature Publishing Group. 2015;12:115–21.

Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 2015;43:e47–7.

Bolotin DA, Poslavsky S, Davydov AN, Frenkel FE, Fanchi L, Zolotareva OI, et al. Antigen receptor repertoire profiling from RNA-seq data. Nat Biotechnol. 2017;35:908–11.

Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39:1–10.

Galon J, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C, et al. Towards the introduction of the “Immunoscore” in the classification of malignant tumours. Jubb A, Koeppen H, Reis-Filho J, editors. J Pathol. John Wiley & Sons, Ltd; 2014;232:199–209.

de Melo GD, Jardim DLF, Marchesi MSP, Hortobagyi GN. Mechanisms of resistance and sensitivity to anti-HER2 therapies in HER2+ breast cancer. Oncotarget Impact Journals. 2016;7:64431–46.

Ríos-Luci C, García-Alonso S, Díaz-Rodríguez E, Nadal-Serrano M, Arribas J, Ocaña A, et al. Resistance to the Antibody-drug conjugate T-DM1 is based in a reduction in lysosomal proteolytic activity. Cancer Res. 2017;77:4639–51.

Rios-Doria J, Harper J, Rothstein R, Wetzel L, Chesebrough J, Marrero A, et al. Antibody-drug conjugates bearing Pyrrolobenzodiazepine or Tubulysin payloads are immunomodulatory and synergize with multiple immunotherapies. Cancer Res. American Association for Cancer Research. 2017;77:2686–98.

Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science. 2018;359:1350–5.

Pfirschke C, Engblom C, Rickelt S, Cortez-Retamozo V, Garris C, Pucci F, et al. Immunogenic chemotherapy sensitizes tumors to checkpoint blockade therapy. Immunity. 2016;44:343–54.