CD7-directed chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising cellular immunotherapy for patients with relapsed or refractory T-cell acute lymphoblastic leukemia and lymphoma (T-ALL/LBL), a population with limited treatment options and poor prognosis. While early clinical outcomes have demonstrated strong antitumor activity, the process of immune reconstitution following CD7 CAR-T therapy remains insufficiently understood, particularly in relation to infection risk and disease relapse.

To address this knowledge gap, GoBroad Healthcare Group investigators conducted an open-label phase I CAR-T clinical trial to evaluate the safety, efficacy, and immune recovery dynamics of donor-derived CD7 CAR-T cells in patients with relapsed or refractory T-ALL/LBL. This study represents an important step toward optimizing CAR-T treatment strategies for aggressive T-cell malignancies.

All treated patients achieved complete remission within 28 days after CD7 CAR-T infusion, highlighting the potent antileukemic efficacy of CD7-targeted CAR-T therapy in this high-risk setting. Robust in vivo expansion of CAR-T cells was observed in all patients, confirming effective target engagement and cellular persistence. As expected, CD7-positive T cells were rapidly eliminated following infusion, while CD7-negative T cells expanded markedly in peripheral blood, becoming a dominant component of post-treatment T-cell immunity.

To better characterize post–CAR-T immune reconstitution, single-cell RNA sequencing was used to profile immune cell populations at high resolution. The analysis revealed that CD7-negative T cells exhibited enhanced immunologic activity compared with pre-infusion T cells, with upregulation of T-cell functional pathways and immune activation signatures. Notably, autoimmune-related pathways were also enriched, suggesting that immune homeostasis after CD7 CAR-T therapy is reshaped rather than simply restored.

Despite encouraging efficacy, infectious complications remained a significant clinical concern. Hematologic toxicities such as leukopenia, neutropenia, and thrombocytopenia were common, and infections occurred in the majority of patients. Importantly, loss of monocytes was identified in patients who developed fatal infections, indicating that impairment of innate immunity may be a key driver of infection risk after CAR-T therapy. These findings underscore the importance of close immune monitoring and supportive care during immune recovery following cellular immunotherapy.

In addition to immune reconstitution, this study provided insights into relapse biology after CD7 CAR-T treatment. The inflammatory proteins S100A8 and S100A9 were found to be significantly upregulated in leukocyte populations from patients who experienced relapse, suggesting their potential role as biomarkers for early relapse detection. Identification of such biomarkers may improve post–CAR-T surveillance and guide timely therapeutic intervention.

Overall, this study delineates the cellular and molecular dynamics of immune recovery after CD7 CAR-T therapy for relapsed or refractory T-ALL/LBL. By integrating clinical outcomes with single-cell immune profiling, the findings offer valuable guidance for improving CAR-T therapy safety, managing infection risk, and refining long-term disease monitoring. This work highlights GoBroad Healthcare Group’s commitment to advancing innovative CAR-T research and translating cutting-edge immunotherapy into meaningful clinical benefit for patients with aggressive T-cell leukemias and lymphomas.

 

Refer to the original:https://doi.org/10.1158/1078-0432.CCR-22-2924