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Immunotherapy


Figure 1


attack, a wider range of cancer cells than adaptive immune cells and antibodies. Second, innate immune cells can help the adaptive immune system better discover and destroy its specific targets in a variety of ways. These include: l Macrophages and DCs, which can attract and activate cells of the adaptive immune system, including B- and T-lymphocytes, that, in turn, kill cancer cells. l Macrophages and NK cells, which kill cells marked by antibodies produced by B-cells.


Drug Discovery World Spring 2019


l Macrophages and DCs, which present antigens from cancer cells they kill that then activate T-cells against those cancer cells Evidence suggests combining innate immune


modulators with established adaptive immunother- apies, such as tumour-targeted antibodies and T- cell checkpoint inhibitors, enhances the activity and longevity of treatments and may expand the population of patients who respond to immunotherapy (Figure 1). As our understanding of the innate immune


References 1 Liu, J, Wang, L, Zhao, F et al. Pre-Clinical Development of a Humanized Anti-CD47 Antibody with Anti-Cancer Therapeutic Potential. PLoS One 2015; 10: e0137345. 2 Majeti, R, Chao, MP, Alizadeh, AA et al. CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell 2009; 138: 286-299. 3Willingham, SB, Volkmer, JP, Gentles, AJ et al. The CD47- signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors. Proc Natl Acad Sci U S A 2012; 109: 6662- 6667. 4 Chao, MP, Alizadeh, AA, Tang, C et al. Anti-CD47 antibody synergizes with rituximab to promote phagocytosis and eradicate non-Hodgkin lymphoma. Cell 2010; 142: 699-713. 5 Sikic, BI, Lakhani, NJ, Patnaik, A et al. A first-in-class, first-in- human phase 1 pharmacokinetic (PK) and pharmacodynamic (PD) study of Hu5F9-G4, an anti-CD47 monoclonal antibody (mAb), in patients with advanced solid tumors. J Clin Oncol 2018; 36: 3002-3002. 6Vyas, P, Knapper, S, Kelly, R et al. Initial Phase 1 Results Of The First-In-Class Anti-CD47 Antibody Hu5F9-G4 In Relapsed/Refractory Acute Myeloid Leukemia Patients. EHA Learning Center 2018; 214718. 7 Advani, RH, Flinn, I, Popplewell, L et al. CD47 Blockade by Hu5F9 and Rituximab in Non-Hodgkin’s Lymphoma. N Engl J Med, 2018; 379: 1711-1721. 8 Crump, M, Neelapu, SS, Farooq, U et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood 2017; 130: 1800- 1808.


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