CD19/CD22 CAR T-cells / National Cancer Institute - LARVOL DELTA

Single-cell metabolic profiling of post-infusion CD22 and CD19/CD22 CAR T-cells reveals a shift toward amino acid–driven oxphos informing SLC-armored CAR design (ASH 2025) - P1 | "However, the metabolic pathways that support CAR T cell persistence and functionin vivo after infusion into patients remain poorly defined.To address this gap, we developed a comprehensive immuno-metabolic pipeline combining single-cellmetabolic assays and plasma metabolomics to analyze CAR T-cells from patients enrolled in CD22 andCD19/CD22 CAR clinical trials for relapsed/refractory B-ALL (NCT02315612, NCT03448393, NCT05098613).Initial high-throughput profiling of healthy donor–derived CD19, CD22, and CD33 CAR T-cells,incorporating either CD28 or 4-1BB costimulatory domains, revealed construct-specific metabolic andfunctional phenotypes. Guidedby these results, we engineered "MetaboArm" CAR T cells co-expressing SLC transporters to enhanceamino acid uptake and improve metabolic fitness. Constructs incorporating glutamine or argininetransporters—SLC1A5, SLC7A1, or SLC38A9—significantly increased OXPHOS activity and enhanced anti-leukemic efficacy both in..."

CAR T-Cell Therapy • Hematological Malignancies • CD22 • CD33 • CD8 • IL7R • SLC1A5

Impact of Prior Chimeric Antigen Receptor T-Cell Therapy on Subsequent Treatment Lines in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (JADPRO 2025) - P1/2 | "She was referred for consideration of a phase 1/2 clinical trial of bicistronic CD19/CD22 CAR T-cell therapy ((NCT05442515)...Most notably: Patient received axi-cel approximately 1 year prior to the visit with us Patient received epcoritamab 3.5 months after axi-cel Patient then received her first bendamustine infusion 5 months after starting epcoritamab (a Bi-specific T-cell engager) and 3 months before this visit with us Disease burden PET scan showed: Involvement of R lung parenchyma, bilateral chest wall/ribs, liver, kidneys, nodal vs pancreatic body lesion at upper abdomen, and axial skeleton/bone marrow Bone marrow biopsy showed no evidence of lymphoma Tissue biopsy was obtained to right chest wall sofit tissue mass Peripheral blood and apheresis product analysis PB flow cytometry detected 50.3% residual CD19 CAR (figure 1)...What is bendamustine's (or any other lymphotoxic chemotherapy) influence CAR T-cell efficacy and outcomes? What is the impact of..."

CAR T-Cell Therapy • IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • CCR7 • CD19 • CD20 • CD22 • CD79A • CD8 • ENTPD1 • IL7R • PD-1 • PD-L1

CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22-expressing B Cell Malignancies (clinicaltrials.gov) - P1 | N=44 | Completed | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Completed | N=150 ➔ 44 | Trial completion date: Dec 2040 ➔ Jan 2025 | Trial primary completion date: Dec 2025 ➔ Jul 2024

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • CD22

Efficient manufacturing of CAR-T cells from whole blood: a scalable approach to reduce costs and enhance accessibility in cancer therapy. (PubMed, Cytotherapy) - "Therapeutically relevant doses of CD19/CD22 CAR-T cells can be successfully manufactured from whole blood. On average, 80 mL of whole blood yields enough CAR-T cells to create a single dose for a pediatric patient (50 kg) at a dosage of 1 × 106 CAR-T cells/kg. For larger patients, scaling up is straightforward by collecting a larger blood volume. This method also demonstrates a cost-effective approach to T cell activation and expansion which, alongside a more straightforward collection of whole blood, makes it more widely accessible especially for middle- and low-income countries. By reducing costs and labor, this strategy has the potential to significantly expand global access to CAR-T cell therapy."

CAR T-Cell Therapy • Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Pediatrics • CD22 • IL2

Modified Immune Cells (CD19-CD22 CAR T Cells) in Treating Patients With Recurrent or Refractory CD19 Positive, CD22 Positive Leukemia or Lymphoma (clinicaltrials.gov) - P1/2 | N=0 | Withdrawn | Sponsor: M.D. Anderson Cancer Center | N=30 ➔ 0 | Trial completion date: Aug 2023 ➔ Nov 2022 | Not yet recruiting ➔ Withdrawn | Trial primary completion date: Aug 2023 ➔ Nov 2022

CAR T-Cell Therapy • Enrollment change • Immune cell • Metastases • Trial completion date • Trial primary completion date • Trial withdrawal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD22

Investigating Whole Blood as a Starting Material for CAR-T Cell Manufacturing (ASGCT 2023) - P1 | "From a minimum of 29 mL of whole blood and 5-10x106starting CD3+ cells, we achieved a median day 7 T-cell yield of 105x106 (range 61 x106-188 x106) with 66% mean transduction efficiency, ultimately producing a median of 69.3 x106 transduced CAR-T cells (range 40.3 x106-124 x106). An ongoing clinical trial at the NIH Clinical Center utilizing the same CAR tested here (clinicaltrials.gov NCT03448393) has a safe and effective dose of 3x106 cells/ kg with an average patient weight of 60 kg. We show here that this therapeutic dose is attainable with a whole blood starting product given the scalability of the system and the fact that we can safely draw larger volumes of blood."

CAR T-Cell Therapy • IO biomarker • Oncology • Pain • Pediatrics • ANXA5 • CCR7 • CD19 • CD22 • IL2 • IL2RA • LAG3 • PD-1 • SELL • TNFA

CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22-expressing B Cell Malignancies (clinicaltrials.gov) - P1 | N=140 | Recruiting | Sponsor: National Cancer Institute (NCI) | N=87 ➔ 140

Enrollment change • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • CD22

Modified Immune Cells (CD19-CD22 CAR T Cells) in Treating Patients With Recurrent or Refractory CD19 Positive, CD22 Positive Leukemia or Lymphoma (clinicaltrials.gov) - P1/2 | N=30 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center | Trial primary completion date: Aug 2022 ➔ Aug 2023

CAR T-Cell Therapy • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • CD22

CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22-expressing B Cell Malignancies (clinicaltrials.gov) - P1; N=87; Recruiting; Sponsor: National Cancer Institute (NCI); Trial completion date: Dec 2032 ➔ Dec 2040; Trial primary completion date: Dec 2022 ➔ Dec 2025

Clinical • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • CD22 • PCR

CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22-expressing B Cell Malignancies (clinicaltrials.gov) - P1; N=87; Recruiting; Sponsor: National Cancer Institute (NCI); Trial primary completion date: Dec 2021 ➔ Dec 2022

Clinical • Trial primary completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • CD22 • PCR

Modified Immune Cells (CD19-CD22 CAR T Cells) in Treating Patients With Recurrent or Refractory CD19 Positive, CD22 Positive Leukemia or Lymphoma (clinicaltrials.gov) - P1/2; N=30; Not yet recruiting; Sponsor: M.D. Anderson Cancer Center; Initiation date: Nov 2019 ➔ Nov 2020

Clinical • Trial initiation date • Acute Lymphocytic Leukemia • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Modified Immune Cells (CD19-CD22 CAR T Cells) in Treating Patients With Recurrent or Refractory CD19 Positive, CD22 Positive Leukemia or Lymphoma (clinicaltrials.gov) - P1/2; N=30; Not yet recruiting; Sponsor: M.D. Anderson Cancer Center

Clinical • New P1/2 trial