More than 50 publications
Our research has been showcased at prestigious conferences like the European Hematology Association and the American Society of Hematology, and over 50 clinical trial-related manuscripts have been published in top-tier journals.
The company's scientific achievements have been acknowledged with First Prizes in Zhejiang Provincial Science and Technology Progress Awards in 2020 and 2023.
Check below some of our published papers.
Sequential CD7 CAR T-Cell Therapy and Allogeneic HSCT without GVHD Prophylaxis
After CAR T-cell therapy, all 10 patients had complete remission with incomplete hematologic recovery and grade 4 pancytopenia. After haploidentical HSCT, 1 patient died on day 13 of septic shock and encephalitis, 8 patients had full donor chimerism, and 1 patient had autologous hematopoiesis.
Three patients had grade 2 HSCT-associated acute GVHD. The median follow-up was 15.1 months (range, 3.1 to 24.0) after CAR T-cell therapy. Six patients remained in minimal residual disease-negative complete remission; 2 had a relapse of CD7-negative leukemia, and 1 died of septic shock at 3.7 months.
The estimated 1-year overall survival was 68% (95% confidence interval [CI], 43 to 100), and the estimated 1-year disease-free survival was 54% (95% CI, 29 to 100).
Donor-Derived CD7 Chimeric Antigen Receptor T Cells for T-Cell Acute Lymphoblastic Leukemia: First-in-Human, Phase I Trial
Twenty participants received infusions. Adverse events including cytokine release syndrome grade 1-2 occurred in 90% (n = 18) and grade 3-4 in 10% (n = 2), cytopenia grade 3-4 in 100% (n = 20), neurotoxicity grade 1-2 in 15% (n = 3), graft-versus-host disease grade 1-2 in 60% (n = 12), and viral activation grade 1-2 in 20% (n = 4).
All adverse events were reversible, except in one patient who died through pulmonary hemorrhage related to fungal pneumonia, which occurred at 5.5 months postinfusion. Ninety percent (n = 18) achieved complete remission of 6.3 months (range, 4.0-9.2), and 15 remained in remission. CAR T cells were still detectable in five of five patients assessed in month 6, postinfusion.
Although patients' CD7-positive normal T cells were depleted, CD7-negative T cells expanded and likely alleviated treatment-related T-cell immunodeficiency.
Allogenic and autologous anti-CD7 CAR-T cell therapies in relapsed or refractory T-cell malignancies
Ten patients were treated, and 5 received autologous CAR-T therapies. No dose-limiting toxicity or neurotoxicity was observed. Grade 1-2 cytokine release syndrome occurred in 7 patients, and grade 3 in 1 patient. Grade 1-2 graft-versus-host diseases were observed in 2 patients.
Seven patients had bone marrow infiltration, and 100% of them achieved complete remission with negative minimal residual disease within one month. Two-fifths of patients achieved extramedullary or extranodular remission.
The median follow-up was 6 (range, 2.7-14) months, and bridging transplantation was not administered. Patients treated with allogeneic CAR-T cells had a higher remission rate, less recurrence, and more durable CAR-T survival than those receiving autologous products. Allogeneic CAR-T cells appeared to be a better option for patients with T-cell malignancies.
Long-term follow-up of donor-derived CD7 CAR T-cell therapy in patients with T-cell acute lymphoblastic leukemia
Twenty participants were enrolled and received infusions with CD7 CAR T cells. After a median follow-up time of 27.0 (range, 24.0-29.3) months, the overall response rate and complete response rate were 95% (19/20 patients) and 85% (17/20 patients), respectively, and 35% (7/20) of patients proceeded to SCT. Six patients experienced disease relapse with a median time-to-relapse of 6 (range, 4.0-10.9) months, and 4 of these 6 patients were found to have lost CD7 expression on tumor cells.
Progression-free survival (PFS) and overall survival (OS) rates 24 months after treatment were respectively 36.8% (95% CI, 13.8-59.8%) and 42.3% (95% CI, 18.8-65.8%), with median PFS and OS of respectively 11.0 (95% CI, 6.7-12.5) months and 18.3 (95% CI, 12.5-20.8) months. Previously reported short-term adverse events (< 30 days after treatment) included grade 3-4 cytokine release syndrome (CRS; 10%) and grade 1-2 graft-versus-host disease (GVHD; 60%).
Serious adverse events reported > 30 days after treatment included five infections and one grade 4 intestinal GVHD. Despite good CD7 CAR T-cell persistence, non-CAR T and natural killer cells were predominantly CD7-negative and eventually returned to normal levels in about half of the participants.
Single-Cell Transcriptomic Analysis Reveals BCMA CAR-T Cell Dynamics in a Patient with Refractory Primary Plasma Cell Leukemia
Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized the clinical treatment of hematological malignancies due to the prominent anti-tumor effects. B cell maturation antigen (BCMA) CAR-T cells have demonstrated promising effects in patients with relapsed/refractory multiple myeloma. However, the dynamics of CAR-T cell proliferation and cytotoxicity in clinical patients remains unexplored.
Here, we longitudinally profiled the transcriptomes of 55,488 T cells, including CAR-T products, CAR-T cells, and endogenous T cells at the peak and remission phases in a plasma cell leukemia (PCL) patient treated with BCMA CAR-T cells by single-cell transcriptomic analysis. Our results showed distinct CAR-T and endogenous T cell subsets indicating stage-specific expression in proliferation, cytotoxicity, and intercellular signaling pathways.
Anti-G Protein-Coupled Receptor, Class C Group 5 Member D Chimeric Antigen Receptor T Cells in Patients With Relapsed or Refractory Multiple Myeloma: A Single-Arm, Phase Ⅱ Trial
From September 1, 2021, to March 23, 2022, 33 patients were infused with anti-GPRC5D CAR T cells. At a median follow-up of 5.2 months (range, 3.2-8.9), the overall response rate was 91% (95% CI, 76 to 98; 30 of 33 patients), including 11 (33%) stringent complete responses, 10 (30%) complete responses, four (12%) very good partial responses, and five (15%) partial responses.
Partial responses or better were observed in nine (100%) of nine patients with previous anti-B-cell maturation antigen (BCMA) CAR T-cell therapy, including two patients who had received repeated anti-BCMA CAR T-cell infusions with no responses at the last time. Grade 3 or higher hematologic toxicities were neutropenia (33 [100%]), anemia (17 [52%]), and thrombocytopenia (15 [45%]).
Cytokine release syndrome occurred in 25 (76%) of 33 patients (all were grade 1 or 2), and neurotoxicities in three patients (one grade 2 and one grade 3 ICANSs and one grade 3 headache).