In a univariate analysis, there were ten factors associated with infection, including tumor load, lymphodepleting chemotherapy, neutrophil deficiency and lymphocyte reduction, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), etc. In a multivariate analysis, CRS ≥ grade 3 was identified as a risk factor for infection (hazard ratio = 2.41, 95% confidence interval: 1.08-5.36, P = 0.031). Therefore, actively reducing the CRS grade may decrease the risk of infection and improve the long-term quality of life of these patients.

pH has potential to serve as an informative factor in predicting CAR T-cell quality and clinical outcomes. Thus, its active monitoring during manufacturing may ensure a more effective CAR T-cell product.

No abstract available

P=N/A, N=353, Recruiting, Beijing GoBroad Hospital | Not yet recruiting --> Recruiting

P1/2, N=42, Recruiting, Seattle Children's Hospital | Trial completion date: Feb 2039 --> Feb 2040 | Trial primary completion date: Jun 2024 --> Jun 2025

P=N/A, N=353, Not yet recruiting, Beijing GoBroad Hospital

P1, N=120, Recruiting, Stanford University | Not yet recruiting --> Recruiting

P1, N=120, Not yet recruiting, Stanford University

Duration of response was overall limited (median 77 days), and CD22 expression was downregulated in 4/12 (33%) available samples at relapse. In summary, we demonstrate that closed-loop manufacturing of CD22-CAR T cells is feasible and is associated with a favorable safety profile and high CR rates in pediatric and adult r/r B-ALL, a cohort with limited CD22-CAR reporting.

P1/2, N=50, Not yet recruiting, Juventas Cell Therapy Ltd. | Initiation date: Oct 2023 --> Aug 2024

P1/2, N=80, Not yet recruiting, Juventas Cell Therapy Ltd. | Initiation date: Oct 2023 --> Aug 2024

P1, N=36, Recruiting, Sumithira Vasu | Trial primary completion date: Dec 2023 --> Dec 2024

P1, N=52, Active, not recruiting, Stanford University | Trial completion date: Dec 2024 --> Dec 2037

P1, N=35, Not yet recruiting, Sana Biotechnology

P1, N=56, Active, not recruiting, Crystal Mackall, MD | Recruiting --> Active, not recruiting

P1, N=10, Active, not recruiting, Stanford University | Suspended --> Active, not recruiting | N=52 --> 10 | Trial completion date: Aug 2035 --> Sep 2036 | Trial primary completion date: Aug 2025 --> Oct 2023

Notably, though, CD22 CART generated from both selection protocols efficiently eradicated leukemia in NSG mice, with negatively selected cells exhibiting a significant enrichment in γδ CD22 CART. Thus, our study demonstrates the importance of the initial T cell selection process in clinical CART manufacturing.

P1, N=123, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting

P1, N=52, Active, not recruiting, Stanford University | Recruiting --> Active, not recruiting | N=92 --> 52 | Trial completion date: Sep 2034 --> Dec 2024 | Trial primary completion date: Apr 2023 --> Dec 2024

P1/2, N=73, Completed, Autolus Limited | Active, not recruiting --> Completed | Trial completion date: Nov 2024 --> Dec 2023 | Trial primary completion date: Nov 2024 --> Dec 2023

P1, N=52, Suspended, Stanford University

P1/2, N=24, Recruiting, Shanxi Province Cancer Hospital | Trial completion date: Dec 2023 --> Oct 2025 | Trial primary completion date: Dec 2021 --> Oct 2024

P1/2, N=93, Recruiting, Stephan Grupp MD PhD | Trial completion date: Jan 2026 --> Jan 2029 | Trial primary completion date: Jan 2025 --> Jan 2027

This information can provide real-time guidance to patients, families, and providers on expectations. Additionally, CD4+CD127+ cells in the starting material appear to be necessary to overcome high disease burden, suggesting the importance of optimized manufacturing to expand this favorable cell subset.

Conclusion While different expansion patterns were observed, CD22 CAR T-cells manufactured in the Prodigy were as safe and effective as those made by bag culture. As commercial CAR T-cells move to automated manufacture, CAR T-cell phenotype, expansion, and functionality especially in patients with EMD may require further study.

P1, N=19, Completed, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine | Recruiting --> Completed | Trial completion date: Aug 2022 --> Nov 2023 | Trial primary completion date: Aug 2022 --> Nov 2023

All patients received lymphodepletion with fludarabine (30 mg/m2 /d) and cyclophosphamide (300 mg/m2 /d) -based conditioning regimens on day −5 to −3...Among them, 8 patients with CML-LBC and 92 ph+ ALL patients received single CD19 CAR T therapy, others received tandem CD19/CD22 CAR T. The baseline characteristics of all patients were shown in Table 1... Worser sustained antitumor efficacy and long-term survival with CAR T-cells therapy in patients with CML-LBC compared to ph+ ALL patients, and ABL kinase region mutation is an independent risk factor for CR and LFS.

The median age of the Targeted drugs group is older than that of the other two groups, 73. 3%, 100% and 41. 2% patients were secondary CNS lymphoma in ASCT+CAR-T group, CAR-T group and Targeted drugs group, respectively.

P1/2, N=20, Recruiting, Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd | Trial completion date: Jan 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=123, Recruiting, CARGO Therapeutics | Not yet recruiting --> Recruiting

P1, N=123, Suspended, National Cancer Institute (NCI) | N=208 --> 123 | Recruiting --> Suspended

This sequential strategy induced deep and sustained responses with an acceptable toxicity profile, and thus potentially provides long-term benefits for children with this condition.

The fludarabine, cyclophosphamide, and alemtuzumab (FCA) LD regimen was also shown to extend host lymphocyte suppression and improve UCART22 expansion versus fludarabine and cyclophosphamide (FC) alone (Boissel N, et al...Cytokine release syndrome (CRS) occurred in 2/3 (67%) pts, with one G1 that resolved without treatment and one G2 that resolved after tocilizumab x1...Pt 3 was refractory to treatment, however this pt received bridging therapy with dasatinib for his ABL2 fusion, and on Day -1, only 47% of the leukemic cells expressed CD22 (down from 88% at screening)... As of 01 July 2023, 3 pts were enrolled into the first UCART22 P2 cohort at DL2. Pt 1 is a 17yo female with B-ALL with a hypodiploid karyotype and a germline TP53 mutation whose disease had previously failed to respond to multiagent chemotherapy, blinatumomab (blina), inotuzumab (ino), venetoclax (ven), allogeneic hematopoietic stem cell transplantation (HSCT), and autologous CD19 CAR T-cell therapy (CAR19) x2. Pt 2 is a 68yo female with Ph-negative B-ALL who relapsed with CD19-low disease after multiagent chemotherapy, ino, and blina.

Patients most commonly received high-dose glucocorticoids, tocilizumab and anakinra. Additional agents for grade 4 IEC-HS included anti-thymoglobulin, dasatanib and emapalumab...The observed IFN-γ cytokine signature is consistent with myeloid cell activation and Th1 T-cell skewing that likely contributes to IEC-HS pathogenesis. These cytokines may be amenable to therapeutic intervention and further study of approaches targeting JAK/STAT and IFN-γ are warranted.

A total of 5 patients with severe cytokine release syndrome (Grade ≥ 3) were observed, including 2 patients in the single CD19 CAR-T group, 2 patients in the tandem CD19/CD22 CAR-T group, and 1 patient in the sequential CD19 and CD22 CAR-T group. Of the 23 patients who achieved CR, 4 patients bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 3 patients received decitabine (DAC) consolidation.With the median follow-up of 25.5 months (range, 1.1 to 33.5), the 2-year overall survival, leukemia-free survival (LFS) and cumulative incidence of relapse rates were 23.7%, 30.5% and 69.5%, respectively. Multivariate Cox regression analyses showed that a better LFS related to the absence of high-risk cytogenetics and genetic characteristics, DAC combination with fludarabine and cyclophosphamide lymphodepletion regimen, and bridging allo-HSCT or DAC consolidation. Our study showed that the second infusion of tandem CD19/CD22 CAR-T therapy obtains a better response than other infusion strategies. Bridging allo-HSCT or DAC consolidation had a significant survival benefit in patients with CR after the second CAR-T therapy.

Serial serum samples from pts enrolled on two clinical trials of the murine CART19 CTL019 (NCT01626495 & NCT02906371) and CART22 (NCT02650414) were examined...All pts who received CART22 had previously received CD19 directed immunotherapy (CART19 N=16, blinatumomab N=1)... Comparing comprehensive serum proteomic profiling between CART19 and CART22 pts we make several novel observations. First, IL-10 levels are significantly higher in CART22 pts at pre-infusion, suggesting that previous immunotherapy has caused an upregulation of this anti-inflammatory cytokine. Second, we show that IL-10 levels have a differential impact on IFNγ levels in CART19 vs CART22 cells.

Results also demonstrate that the HIP approach to generate allogeneic CAR T cells that evade innate and adaptive immune rejection can be expanded as a platform to generate CAR T cells against target antigens alternative to CD19. Collectively, the data suggest that CD22 HIP CAR T cells display a combination of antigen-specific pharmacologic activity and immune evasion that support their progression into human clinical studies for the treatment of CD19 CAR T cell-refractory patients.

TALEN® gene editing technology is used to inactivate the TRAC and CD52 genes to minimize graft-versus-host disease (GvHD) and allow for the use of alemtuzumab (CLLS52, an anti-CD52 monoclonal antibody) in the lymphodepletion (LD) regimen, respectively...After LD with FCA (fludarabine 30 mg/m2 × 3d, cyclophosphamide 0.5g/m2 × 3d, CLLS52 12 mg on D1, 24 mg on D2, D3), a single infusion of UCART20x22 is administered at a flat dose level ([DL1] 50 x 106 cells; [DL2] 150 x 106 cells; and [DL3] 450 x 106 cells)...Pt 3 is an 18yo female with R/R DLBCL transformed from marginal zone lymphoma who previously received chemoimmunotherapy, venetoclax, ibrutinib, BR, CAR19, obinutuzumab, glofitamab, tafasitamab, lenalidomide, and an experimental epigenetic modifier...Pt 1 had G1 CRS and received tocilizumab (toci) x3 and dexamethasone (dex) x1... As of 01 July 2023, 3 pts were enrolled and treated at DL1. Pt 1 is a 76yo female with double-expressor diffuse large B-cell lymphoma (DLBCL) relapsed after R-CHOP, radiation therapy, and polatuzumab vedotin with bendamustine/rituximab (BR) and was considered ineligible for CAR19 due to recent high dose bendamustine. Pt 2 is a 65yo female with R/R triple-hit lymphoma transformed from follicular lymphoma who was previously treated with radiation therapy, BR, dose-adjusted R-EPOCH, and two separate CAR19 treatments.

P1, N=78, Active, not recruiting, Seattle Children's Hospital | Recruiting --> Active, not recruiting

P1/2, N=40, Recruiting, Cellectis S.A. | Trial primary completion date: Jul 2023 --> Dec 2023

The utilization of CRISPR/ Cas9 technology facilitated highly efficient and precise gene editing, resulting in the production of universal CAR-T cells. No genotoxicity or chromosomal translocation associated with gene editing was observed. Six patients received infusions of CTA101 at doses of 1 (3 patients) and 3 (3 patients) × 106 CAR+ T cells per kilogram of body weight.

P1, N=48, Active, not recruiting, Medical College of Wisconsin | Recruiting --> Active, not recruiting