Preclinical findings presented in the Plenary Session at EHA 2026 suggest that CD5 inhibition may serve as a broadly applicable sensitization strategy for T-cell engager therapies, with activity observed across leukemia, lymphoma, myeloma, and solid tumor models
“Maybe we should shift our focus from tumor cells to T cells. If we can identify ways to improve T-cell function, that could apply across many different tumor types.”
touchHEMATOLOGY coverage from EHA 2026
Abstract EHA-4564: Wang W, Zhao H, Yang X, et al. CD5 INHIBITION AS A GENERALIZABLE STRATEGY TO AMPLIFY T CELL-MEDIATED ANTI-TUMOR EFFECTS OF BISPECIFIC T-CELL ENGAGERS. Presented at: EHA 2026, Stockholm, Sweden. June 11–14th, 2026.
New data presented at the European Hematology Association (EHA) 2026 Congress by Prof Yizhen Li (Children’s Hospital of Soochow University, Suzhou, China) identify CD5 as a key intrinsic regulator of T-cell engager (TCE) efficacy, with potential implications across both hematologic malignancies and solid tumors. In the plenary abstract, investigators used genome-wide and targeted CRISPR knockout screens in primary human CD8+ T cells exposed to the CD19×CD3 bispecific Blinatumomab to identify T cell–intrinsic mechanisms limiting response.
CD5 emerged as a negative regulator of T-cell activation. Genetic deletion or antibody blockade of CD5 enhanced blinatumomab-mediated cytotoxicity, increased proliferation, and augmented cytokine production, including IFNγ and TNFα. Mechanistically, CD5 inhibition enriched IL2–STAT5, TNFα–NF-κB, and MTORC1 signaling and increased ERK and S6 phosphorylation. Importantly, the effect extended beyond B-ALL to multiple CD3-engaging bispecifics targeting CD20, BCMA, GPRC5D, DLL3, and GD2, supporting CD5 as a potentially generalizable therapeutic target for amplifying TCE efficacy.
Following her presentation, Li spoke about the translational implications of the findings.
What are the biggest takeaways from this research?
The biggest takeaway message is that inhibition of CD5 is a way to increase the sensitivity of multiple T-cell engagers. These TCEs target multiple tumor types and multiple tumor surface antigens.
CD5 is a very important negative regulator of T cells. This means we should pay more attention to the T cell itself. With T-cell engagers, CAR T-cell therapies, and other immunotherapies, T-cell function is critical. Maybe we should shift our focus from tumor cells to T cells. If we can identify ways to improve T-cell function, that could apply across many different tumor types.
Which tumor types have you explored beyond B-ALL?
We tested other tumor types including multiple myeloma, lymphoma, and neuroblastoma. We also tested lung cancer, although we did not include those data in the presentation because it is outside hematologic malignancies. Across multiple models, the cytotoxicity of TCEs could be increased by CD5 inhibition, either through CD5 knockout or antibody blockade. We used leukemia as a model to identify mechanisms that could increase the efficacy of TCEs. But because TCE function depends on T cells, if we can enhance T-cell activity against leukemia cells, we can apply the same principle to T cells targeting solid tumors. That is why I think targeting CD5 could be useful not only for leukemia but also for other solid tumors.
What unanswered questions remain, and what are the next steps?
One of our next goals is to generate a monoclonal antibody against CD5. However, because CD5 is expressed on T cells, antibody binding could trigger side effects such as antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). That could result in T cells being killed by NK cells. The main challenge will be modifying the Fc fragment of the CD5 antibody to reduce ADCC and CDC while preserving the ability to enhance T-cell function.
The next step is generating a monoclonal CD5 antibody. We want to combine this antibody with multiple T-cell engagers and test whether this can improve responses across different tumor types.
The findings position CD5 as a potentially broad immunomodulatory target capable of augmenting multiple T-cell–dependent therapeutic platforms. While the work remains preclinical, the concept of targeting T cell–intrinsic inhibitory pathways rather than tumor-specific resistance mechanisms may represent a notable shift in the development of next-generation bispecifics and cellular therapies. Future studies will need to establish whether this strategy can preserve tolerability while maintaining enhanced anti-tumor activity in clinical settings.
This content has been developed independently by Touch Medical Media for touchHEMATOLOGY. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media. This article was created by the editorial team utilizing AI as an editorial tool (ChatGPT 5.5 [Large language model]. https://chat.openai.com/chat.) The content was developed and edited by human editors. No funding was received in the publication of this article.
Cite: EHA 2026 news: Could releasing the ‘brake’ on T cells improve bispecific efficacy? touchHEMATOLOGY. 24th June 2026.
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