Science

Hung Trinh: Adapter-CAR T-Cells Targeting CD276 – A Novel Therapy for SCLC Preventing Fratricide

Hung Trinh/LinkedIn

Aug 10, 2025, 08:27

Hung Trinh: Adapter-CAR T-Cells Targeting CD276 – A Novel Therapy for SCLC Preventing Fratricide

Hung Trinh, Senior VP of Operations at Seneca Therapeutics, shared a post on LinkedIn about recent paper published in Journal of Hematology and Oncology:

“Targeting CD276 with Adapter-CAR T-cells provides a novel therapeutic strategy in small cell lung cancer and prevents CD276-dependent fratricide

Methods

In this study, we investigated the expression of CD276 (B7-H3), an immune checkpoint molecule and promising target antigen for CAR-T therapy in SCLC, at the RNA and protein level. We further developed novel Fab-based adapter molecules (AM) targeting CD276 and optimized our previously established modular Adapter CAR-T (AdCAR-T) platform as well as AM dosing schemes.

Results

CD276 is broadly expressed across SCLC subtypes, representing a promising target for CAR-T therapy. We describe that T-cell activation and CAR-signalling induces CD276-expression on CAR-T, resulting in CD276-dependent fratricide, limiting anti-CD276-CAR-T expansion and activity. The AdCAR-T platform allows CAR-T expansion in absence of CD276 targeting.

Novel CD276 targeted AMs demonstrate potent in vitro and in vivo activity against SCLC. Intermittent AM-dosing allows functional persistence of AdCAR-T in vivo in contrast to CD276-targeted conventional CAR-T. AdCAR-T in vivo expansion and activity is further promoted by introducing activation-induced, AM remote controlled, IL-18 secretion into the AdCAR-T design.

Conclusion

We identified CD276 as a promising target antigen, uniformly expressed in SCLC and demonstrate the therapeutic potential of novel anti-CD276 Fab-based AM in combination with optimized, IL-18 armoured AdCAR-T.

Taken together, our results suggest that AdCAR-T is ideally suited to target CD276 in SCLC. Despite its expression on activated T-cells, CD276 remains a highly promising therapeutic target due to its broad and uniform expression across multiple malignancies.

Innovative strategies such as controlled adapter dosing, as demonstrated in this study, or gene editing approaches may provide effective means to overcome CD276-dependent fratricide and maximize therapeutic efficacy. We plan to test our system in a Phase I/II clinical trial evaluating CD276-targeting AdCAR-T in SCLC in patients with complete (CR1) or partial remission (PR1).”

Title: Targeting CD276 with Adapter-CAR T-cells provides a novel therapeutic strategy in small cell lung cancer and prevents CD276-dependent fratricide

Authors: Beate Kristmann, Niels Werchau, Lakshmi Suresh, Elisabeth L. Pezzuto, Sophia Scheuermann, Simon Krost, Karin Schilbach, Moustafa Moustafa-Oglou, Anna-Sophia Mast, Miriam Droste, André Felsberger, Lukas Kiefer, Pierre Abramowski, Lars Zender, Joerg Mittelstaet, Christian M. Seitz

Read The Full Article at Journal of Hematology and Oncology.

Hung Trinh: Adapter-CAR T-Cells Targeting CD276 - A Novel Therapy for SCLC Preventing Fratricide

More posts featuring Hung Trinh on OncoDaily.

André Felsberger Anna-Sophia Mast Beate Kristmann cancer CAR-T cells CD276 Christian M. Seitz Elisabeth L. Pezzuto Hung Trinh Joerg Mittelstaet Karin Schilbach Lakshmi Suresh Lars Zender Lukas Kiefer Miriam Droste Moustafa Moustafa-Oglou Niels Werchau OncoDaily Oncology Pierre Abramowski SCLC Simon Krost Sophia Scheuermann

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