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Fundamental differences exist in the disease phenotype of haematological malignancies and solid cancers, an obvious one being the highly immunosuppressive TME that is a characteristic feature of solid tumours. Major components of the TME of solid tumours include anti-tumour immune cells together with stromal cells, such as cancer-associated fibroblasts (CAFs), T REG cells, myeloid-derived suppressor cells (MDSCs) and tumour-associated macrophages (TAMs), that function in suppressing anti-tumour immunity. 55, 56, 57 Immunosuppressive cytokines and soluble factors including adenosine, IL-10, transforming growth factor β (TGF-β), and indoleamine 2,3-dioxygenase (IDO) also reside in the hostile TME. Targeting the hostile TME in conjunction with CD3+ bispecific T-cell redirection None of these terms affect your legal rights and these are not diminished in any way. If any term is held to be invalid under any applicable statute or rule of law, that term is automatically omitted from the terms to minimum extent necessary to comply with the law and without affecting the validity or enforceability of the remainder Long, J.S.; Ryan, K.M. New frontiers in promoting tumour cell death: Targeting apoptosis, necroptosis and autophagy. Oncogene 2012, 31, 5045–5060. [ Google Scholar] [ CrossRef] [ PubMed]Banaszek, A., Bumm, T. G. P., Nowotny, B., Geis, M., Jacob, K., Wolfl, M. et al. On target restoration of a split T cell-engaging antibody for precision immunotherapy. Nat. Commun. 10, 5387 (2019). Runcie, K., Budman, D. R., John, V. & Seetharamu, N. Bi-specific and tri-specific antibodies—the next big thing in solid tumor therapeutics. Mol. Med. 24, 50 (2018).

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