4.4 Article

Potent preclinical activity of FLT3-directed chimeric antigen receptor T-cell immunotherapy against FLT3-mutant acute myeloid leukemia and KMT2A-rearranged acute lymphoblastic leukemia

Related references

Note: Only part of the references are listed.
Article Hematology

Impact of high-risk cytogenetics on outcomes for children and young adults receiving CD19-directed CAR T-cell therapy

Allison Barz Leahy et al.

Summary: Chimeric antigen receptor (CAR) T-cell therapy is effective in treating relapsed/refractory B-acute lymphoblastic leukemia (ALL), regardless of different cytogenetic characteristics. High-risk patients, including those with KMT2A-rearranged infant ALL, showed high probabilities of relapse-free survival and overall survival at 2 years.

BLOOD (2022)

Article Oncology

CD123 Expression Is Associated With High-Risk Disease Characteristics in Childhood Acute Myeloid Leukemia: A Report From the Children's Oncology Group

Adam J. Lamble et al.

Summary: The expression of CD123 is closely associated with disease-relevant cytogenetic and molecular alterations in childhood AML. Patients with high CD123 expression have higher relapse risk and inferior clinical outcomes compared to conventional therapy. Therefore, CD123 may serve as a critical biomarker and promising immunotherapeutic target for children with relapsed or refractory AML.

JOURNAL OF CLINICAL ONCOLOGY (2022)

Article Oncology

Phase II Trial of Inotuzumab Ozogamicin in Children and Adolescents With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia: Children's Oncology Group Protocol AALL1621

Maureen M. O'Brien et al.

Summary: The study aims to evaluate the efficacy and safety of inotuzumab ozogamicin in pediatric and adolescent patients with relapsed or refractory B-cell acute lymphoblastic leukemia. The results show that inotuzumab ozogamicin is effective and well tolerated in CD22-positive B-ALL patients. Side effects include sinusoidal obstruction syndrome and cytopenias. Partial CD22 expression and lower CD22 site density are associated with decreased response to inotuzumab ozogamicin.

JOURNAL OF CLINICAL ONCOLOGY (2022)

Article Oncology

Sorafenib in Combination With Standard Chemotherapy for Children With High Allelic Ratio FLT3/ITD+ Acute Myeloid Leukemia: A Report From the Children's Oncology Group Protocol AAML1031

Jessica A. Pollard et al.

Summary: The study investigated the feasibility and efficacy of adding sorafenib, a multikinase tyrosine kinase inhibitor, to standard chemotherapy and as single-agent maintenance therapy in pediatric acute myeloid leukemia (AML) with high allelic ratio (HAR) FLT3/ITD mutations. The results showed that sorafenib can be safely added to conventional AML chemotherapy and may improve outcomes in this population. Patients treated with sorafenib had higher survival rates and disease-free survival rates compared to those who did not receive sorafenib.

JOURNAL OF CLINICAL ONCOLOGY (2022)

Article Oncology

A novel IgG-based FLT3xCD3 bispecific antibody for the treatment of AML and B-ALL

Naveen K. Mehta et al.

Summary: Immunotherapeutic strategies using CAR-T cells and bsAbs have achieved remarkable clinical success in lymphoid malignancies but not in acute myeloid leukemia (AML). This study developed a bsAb, CLN-049, targeting FLT3 and demonstrated its favorable efficacy and safety profile in preclinical models, indicating its potential as a treatment option for AML.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2022)

Article Hematology

Combinatorial efficacy of entospletinib and chemotherapy in patient-derived xenograft models of infant acute lymphoblastic leukemia

Joseph P. Loftus et al.

Summary: Constitutive activation of SYK and associated signaling is observed in KMT2A-rearranged ALL with sensitivity to entospletinib both in vitro and in vivo. Combination therapy with vincristine or selumetinib enhances the treatment effects of SYK inhibition.

HAEMATOLOGICA (2021)

Article Hematology

CLEC12A and CD33 coexpression as a preferential target for pediatric AML combinatorial immunotherapy

Semjon Willier et al.

Summary: Emerging immunotherapies like chimeric antigen receptor T cells have shown progress in treating acute lymphoblastic leukemia, but controlling acute myeloid leukemia poses challenges due to differences in clinical and biological characteristics across age groups.

BLOOD (2021)

Article Oncology

Clinical Implications of Minimal Residual Disease Detection in Infants With KMT2A-Rearranged Acute Lymphoblastic Leukemia Treated on the Interfant-06 Protocol

Janine Stutterheim et al.

Summary: MRD levels are predictive of outcomes in infant acute lymphoblastic leukemia, helping to guide treatment interventions.

JOURNAL OF CLINICAL ONCOLOGY (2021)

Article Biochemistry & Molecular Biology

CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial

Shaun Cordoba et al.

Summary: Bicistronic CAR T cells targeting CD19 and CD22 (AUTO3) show clinical activity and low toxicity in patients with B cell acute lymphoblastic leukemia, but relapses may be due to limited CAR T cell persistence, highlighting the need to improve CAR T cell persistence for better efficacy.

NATURE MEDICINE (2021)

Article Oncology

FLT3 inhibitor lestaurtinib plus chemotherapy for newly diagnosed KMT2A-rearranged infant acute lymphoblastic leukemia: Children's Oncology Group trial AALL0631

Patrick A. Brown et al.

Summary: Adding lestaurtinib did not improve event-free survival overall for infants with KMT2A-rearranged acute lymphoblastic leukemia, but patients who achieved potent FLT3 inhibition and had leukemia blasts sensitive to FLT3 inhibition ex vivo did benefit from the addition of lestaurtinib. Patient selection and pharmacodynamics-guided dose escalation may enhance the efficacy of FLT3 inhibition for this subtype of infant ALL.

LEUKEMIA (2021)

Article Biochemistry & Molecular Biology

CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial

Jay Y. Spiegel et al.

Summary: Despite impressive progress in CAR-T cell therapy, more than 50% of patients treated with CD19-targeting CAR-T cells experience disease progression, often associated with antigen loss. To address this issue, researchers tested a bispecific CAR targeting CD19 and/or CD22, which showed high efficacy in preventing relapse in patients with B-ALL and LBCL. Antigen loss was identified as a major cause of CAR T cell resistance, emphasizing the importance of engineering multi-specific CAR T cells with equivalent potency and cytokine production as a quality indicator for potency.

NATURE MEDICINE (2021)

Review Oncology

A comparison of chimeric antigen receptors containing CD28 versus 4-1BB costimulatory domains

Kathryn M. Cappell et al.

Summary: CAR T cell therapies targeting haematological malignancies show promising efficacy, with CD28- and 4-1BB-derived costimulatory domains demonstrating potentially different cellular and clinical effects. Further research is needed to compare their effectiveness and toxicity profiles.

NATURE REVIEWS CLINICAL ONCOLOGY (2021)

Article Oncology

Systematic preclinical evaluation of CD33-directed chimeric antigen receptor T cell immunotherapy for acute myeloid leukemia defines optimized construct design

Haiying Qin et al.

Summary: The development of CAR T cell immunotherapy for AML patients is crucial. Through rigorous preclinical evaluation of CD33 CAR T cells, the best lintuzumab-CD28/CD3 zeta CAR construct was selected for clinical translation, showing potent anti-leukemia activity.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2021)

Article Oncology

Patterns of Resistance Differ in Patients with Acute Myeloid Leukemia Treated with Type I versus Type II FLT3 Inhibitors

Ahmad S. Alotaibi et al.

Summary: The study revealed distinct emergent mutations in FLT3-mutated AML patients treated with FLT3 inhibitors, indicating different pathways of secondary resistance. Furthermore, pretreatment RAS/MAPK mutations may be associated with primary resistance in patients.

BLOOD CANCER DISCOVERY (2021)

Article Oncology

Tuning the Antigen Density Requirement for CAR T-cell Activity

Robbie G. Majzner et al.

CANCER DISCOVERY (2020)

Article Oncology

Characterization of a Novel FLT3 BITE Molecule for the Treatment of Acute Myeloid Leukemia

Bettina Brauchle et al.

MOLECULAR CANCER THERAPEUTICS (2020)

Article Oncology

Modulation of Target Antigen Density Improves CAR T-cell Functionality and Persistence

Sneha Ramakrishna et al.

CLINICAL CANCER RESEARCH (2019)

Review Oncology

Multi-Specific CAR Targeting to Prevent Antigen Escape

Zachary Walsh et al.

CURRENT HEMATOLOGIC MALIGNANCY REPORTS (2019)

Article Education, Scientific Disciplines

Opportunities for immunotherapy in childhood acute myeloid leukemia

Adam J. Lamble et al.

Hematology-American Society of Hematology Education Program (2019)

Article Medicine, General & Internal

Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia

S. L. Maude et al.

NEW ENGLAND JOURNAL OF MEDICINE (2018)

Article Biochemistry & Molecular Biology

Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia

Elena J. Orlando et al.

NATURE MEDICINE (2018)

Article Cardiac & Cardiovascular Systems

FLT3 Activation Improves Post-Myocardial Infarction Remodeling Involving a Cytoprotective Effect on Cardiomyocytes

Otmar Pfister et al.

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY (2014)

Article Hematology

MLL-rearranged leukemias:: Insights from gene expression profiling

SA Armstrong et al.

SEMINARS IN HEMATOLOGY (2003)