Co-infusion of high-dose haploidentical donor cells and CD19-targeted CART cells achieves complete remission, successful donor engraftment and significant CART amplification in advanced ALL

Therapeutic Advances in Medical Oncology
Changlin YuMei Guo

Abstract

Autologous CD19-targeted chimeric antigen receptor-modified T cells (CD19-CART) remarkably improved the outcome of patients with advanced B-cell acute lymphoblastic leukemia (B-ALL). However, the application and outcomes of allogeneic CART cells is still uncertain. Two patients with advanced B-ALL were enrolled to receive a co-infusion of high-dose human leukocyte antigen-haploidentical donor granulocyte colony-stimulating factor mobilized peripheral blood mononuclear cells (GPBMCs; 21.01-25.34 × 108/kg) and the same donor-derived CD19-targeted CART cells (8.44-22.19 × 106/kg) without additional in vitro gene-editing following a reinduction chemotherapy as precondition. They achieved complete remission and full donor chimerism (FDC) with ongoing 20- and 4-month leukemia-free survival. A significant amplification of donor CART cells was detected in peripheral blood and/or cerebrospinal fluid and was associated with the formation of FDC. The highest amount of copies of the donor CART cells reached 4962 per µg of genomic DNA (gDNA) and 2449 per µg of gDNA, and the longest persistence was 20 months associated with B cell aplasia. Two patients experienced Grade II or III cytokine release syndromes and developed controllable Grade II...Continue Reading

References

Dec 13, 2005·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Alexandra H FilipovichMary E D Flowers
Jan 13, 2011·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Michael R BishopSergio Giralt
Oct 16, 2014·The New England Journal of Medicine·Shannon L MaudeStephan A Grupp
Oct 21, 2015·Journal of the National Comprehensive Cancer Network : JNCCN·Joseph C AlvarnasCourtney Smith
Jan 27, 2017·Science Translational Medicine·Waseem QasimPaul Veys
Sep 20, 2017·Nature Reviews. Clinical Oncology·Sattva S NeelapuElizabeth J Shpall
Nov 17, 2017·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Marco Ruella, Saad S Kenderian
Jan 10, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shivani Srivastava, Stanley R Riddell

❮ Previous
Next ❯

Related Concepts

Related Feeds

CAR-T cells

Chimeric antigen receptor (CAR) T cells are cells that are genetically engineered to recognize and target specific proteins. The ability of these cells to recognize cancer antigens and eliminate tumor cells have transformed cancer immunotherapy approaches. Here is the latest research on CAR-T cells.

CSF & Lymphatic System

This feed focuses on Cerebral Spinal Fluid (CSF) and the lymphatic system. Discover the latest papers using imaging techniques to track CSF outflow into the lymphatic system in animal models.

B-Cell Leukemia (Keystone)

B-cell leukemia includes various types of lymphoid leukemia that affect B cells. Here is the latest research on B-cell leukemia.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.