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CD47 blockade enhances therapeutic activity of TCR mimic antibodies to ultra-low density cancer epitopes

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References

  1. Chang AY, Dao T, Gejman RS, Jarvis CA, Scott A, Dubrovsky L et al. A therapeutic T cell receptor mimic antibody targets tumor-associated PRAME peptide/HLA-I anigens. JCI 2017; 127: 2705–2718.

    Article  Google Scholar 

  2. Dao T, Yan S, Veomett N, Pankov D, Zhou L, Korontsvit T et al. Targeting the intracellular WT1 oncogene product with a therapeutic human antibody. Sci Transl Med 2013; 5: 176ra33.

    Article  Google Scholar 

  3. Veomett N, Dao T, Liu H, Xiang J, Pankov D, Dubrovsky L et al. Therapeutic efficacy of an Fc-enhanced TCR-like antibody to the intracellular WT1 oncoprotein. Clin Cancer Res 2014; 20: 4036–4046.

    Article  CAS  Google Scholar 

  4. Dubrovsky L, Pankov D, Brea EJ, Dao T, Scott A, Yan S et al. A TCR-mimic antibody to WT1 bypasses tyrosine kinase inhibitor resistance in human BCR-ABL+ leukemias. Blood 2014; 123: 3296–3304.

    Article  CAS  Google Scholar 

  5. Verma B, Jain R, Caseltine S, Rennels A, Bhattacharya R, Markiewski MM et al. TCR mimic monoclonal antibodies induce apoptosis of tumor cells via immune effector-independent mechanisms. J Immunol 2011; 186: 3265–3276.

    Article  CAS  Google Scholar 

  6. Petrova PS, Viller NN, Wong M, Pang X, Lin GH, Dodge K et al. TTI-621 (SIRPalphaFc): a CD47-blocking innate immune checkpoint inhibitor with broad anti-tumor activity and minimal erythrocyte binding. Clin Cancer Res 2016; 23: 1068–1079.

    Article  Google Scholar 

  7. van den Berg TK, van Bruggen R . Loss of CD47 makes dendritic cells see red. Immunity 2015; 43: 622–624.

    Article  CAS  Google Scholar 

  8. Weiskopf K, Ring AM, Ho CC, Volkmer JP, Levin AM, Volkmer AK et al. Engineered SIRPalpha variants as immunotherapeutic adjuvants to anticancer antibodies. Science 2013; 341: 88–91.

    Article  CAS  Google Scholar 

  9. Parker BS, Rautela J, Hertzog PJ . Antitumour actions of interferons: implications for cancer therapy. Nat Rev Cancer 2016; 16: 131–144.

    Article  Google Scholar 

  10. Liu X, Pu Y, Cron K, Deng L, Kline J, Frazier WA et al. CD47 blockade triggers T cell-mediated destruction of immunogenic tumors. Nat Med 2015; 21: 1209–1215.

    Article  CAS  Google Scholar 

  11. Liu Y, Buhring HJ, Zen K, Burst SL, Schnell FJ, Williams IR et al. Signal regulatory protein (SIRPalpha), a cellular ligand for CD47, regulates neutrophil transmigration. J Biol Chem 2002; 277: 10028–10036.

    Article  CAS  Google Scholar 

  12. Bruhns P . Properties of mouse and human IgG receptors and their contribution to disease models. Blood 2012; 119: 5640–5649.

    Article  CAS  Google Scholar 

  13. Shultz LD, Lyons BL, Burzenski LM, Gott B, Chen X, Chaleff S et al. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J Immunol 2005; 174: 6477–6489.

    Article  CAS  Google Scholar 

  14. Darwich L, Coma G, Pena R, Bellido R, Blanco EJ, Este JA et al. Secretion of interferon-gamma by human macrophages demonstrated at the single-cell level after costimulation with interleukin (IL)-12 plus IL-18. Immunology 2009; 126: 386–393.

    Article  CAS  Google Scholar 

  15. Tanaka S, Saito Y, Kunisawa J, Kurashima Y, Wake T, Suzuki N et al. Development of mature and functional human myeloid subsets in hematopoietic stem cell-engrafted NOD/SCID/IL2rgammaKO mice. J Immunol 2012; 188: 6145–6155.

    Article  CAS  Google Scholar 

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Acknowledgements

Author contributions

MDM—experimental design, animal experiments, drafting of manuscript; JTS—experimental design, in vitro experiments, drafting of manuscript; AYC—Pr20 characterization, biochemistry and immunology, drafting of manuscript; KST—statistical design and analysis; CL—creation and manufacturing of ESK and Pr20; KCG—experimental design, analysis, drafting of manuscript; DAS—experimental design, analysis, drafting of manuscript.

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Correspondence to K C Garcia or D A Scheinberg.

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CL: equity in Eureka; KCG: equity in Alexo Therapeutics; DAS: consultant to Eureka. The remaining authors declare no conflict of interest.

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Supplementary Information accompanies this paper on the Leukemia website

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Mathias, M., Sockolosky, J., Chang, A. et al. CD47 blockade enhances therapeutic activity of TCR mimic antibodies to ultra-low density cancer epitopes. Leukemia 31, 2254–2257 (2017). https://doi.org/10.1038/leu.2017.223

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