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. 2020 Aug 28;6:28. doi: 10.1038/s41540-020-00145-7

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — The QSP model describes the in vivo dynamics of B and T-cells and their interactions in the presence of mosunetuzumab and blinatumomab interactions in the following compartments: a peripheral blood PB, b bone marrow BM, c separate lymph node and spleen compartments, and d an optional NHL tumor compartment. The key biological interactions are labeled in the diagram as follows: (1) migration of newly generated B-cells from BM to PB, (2) Homeostatic thymic generation of new CD8+ T-cells (only when PB T-cells are diminished), (3) homeostatic apoptosis/loss of B-cells (only in BM) and T-cells (only when in excess), (4) T-cell activation due to interaction of bispecific drugs with B and T-cells; for mosunetuzumab, this requires CD20+ B-cells, (5) B-cell death due to T-cell cytolytic activity; for mosunetuzumab, this applies only to CD20+ B-cells, (6) activated T-cell induction of cytokine release, (7) activated T-cell proliferation, (8) interconversion of activated and post-activated T-cells, (9) conversion of post-activated to resting T-cells (e.g., memory cells), (10) activation-related apoptosis of activated and post-activated T-cells, (11) PB T-cell traffic to/from tissues, (12) PB B-cell traffic to replenish normal tissues (only when tissue B-cells are diminished), (13) proliferation of tumor B-cells (constitutive) and normal tissue B-cells (only when diminished), (14) Generation of pro-B-cells from stem cell precursors (15) maturation of CD20- pro-B-cells to CD20+ B-cells. Dotted lines represent mechanisms that do not alter cell states.