Shah, Kavina;
Leandro, Maria;
Cragg, Mark;
Kollert, Florian;
Schuler, Franz;
Klein, Christian;
Reddy, Venkat;
(2024)
Disrupting B and T cell Collaboration in Autoimmune Disease: T cell engagers versus CAR T cell therapy?
Clinical and Experimental Immunology
, Article uxae031. 10.1093/cei/uxae031.
(In press).
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Abstract
B and T cells collaborate to drive autoimmune disease (AID). Historically, B and T cell (B-T cell) co-interaction was targeted through different pathways such as alemtuzumab, abatacept, and dapirolizumab with variable impact on B cell depletion (BCD), whereas the majority of patients with AID including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and organ transplantation benefit from targeted BCD with anti-CD20 monoclonal antibodies such as rituximab, ocrelizumab or ofatumumab. Refractory AID is a significant problem for patients with incomplete BCD with a greater frequency of IgD-CD27+ switched memory B cells, CD19+CD20- B cells and plasma cells that are not directly targeted by anti-CD20 antibodies, whereas most lymphoid tissue plasma cells express CD19. Furthermore, B-T cell collaboration is predominant in lymphoid tissues and at sites of inflammation such as the joint and kidney, where BCD may be inefficient, due to limited access to key effector cells. In the treatment of cancer, chimeric antigen receptor (CAR) T cell therapy and T cell engagers (TCE) that recruit T cells to induce B cell cytotoxicity have delivered promising results for anti-CD19 CAR T cell therapies, the CD19 TCE blinatumomab and CD20 TCE such as mosunetuzumab, glofitamab or epcoritamab. Limited evidence suggests that anti-CD19 CAR T cell therapy may be effective in managing refractory AID whereas we await evaluation of TCE for use in non-oncological indications. Therefore, here, we discuss the potential mechanistic advantages of novel therapies that rely on T cells as effector cells to disrupt B-T cell collaboration toward overcoming rituximab-resistant AID.
| Type: | Article |
|---|---|
| Title: | Disrupting B and T cell Collaboration in Autoimmune Disease: T cell engagers versus CAR T cell therapy? |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/cei/uxae031 |
| Publisher version: | http://dx.doi.org/10.1093/cei/uxae031 |
| Language: | English |
| Additional information: | © The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com |
| Keywords: | CAR T-cell therapy, Systemic lupus erythematosus, T cell engagers, rheumatoid arthritis, rituximab |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10191307 |
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