41BB-based and CD28-based CD123-redirected T-cells ablate human normal hematopoiesis in vivo.

Journal for Immunotherapy of Cancer
Matteo Libero BaroniPablo Menendez

Abstract

Acute myeloid leukemia (AML) is a hematopoietic malignancy which is biologically, phenotypically and genetically very heterogeneous. Outcome of patients with AML remains dismal, highlighting the need for improved, less toxic therapies. Chimeric antigen receptor T-cell (CART) immunotherapies for patients with refractory or relapse (R/R) AML are challenging because of the absence of a universal pan-AML target antigen and the shared expression of target antigens with normal hematopoietic stem/progenitor cells (HSPCs), which may lead to life-threating on-target/off-tumor cytotoxicity. CD33-redirected and CD123-redirected CARTs for AML are in advanced preclinical and clinical development, and they exhibit robust antileukemic activity. However, preclinical and clinical controversy exists on whether such CARTs are myeloablative. We set out to comparatively characterize in vitro and in vivo the efficacy and safety of 41BB-based and CD28-based CARCD123. We analyzed 97 diagnostic and relapse AML primary samples to investigate whether CD123 is a suitable immunotherapeutic target, and we used several xenograft models and in vitro assays to assess the myeloablative potential of our second-generation CD123 CARTs. Here, we show that CD123 rep...Continue Reading

References

Apr 12, 2003·Leukemia & Lymphoma·Tadeusz Robak
Dec 13, 2003·Leukemia·U TestaC Peschle
Dec 10, 2009·The Journal of Experimental Medicine·Pablo MenendezJavier García-Castro
Aug 2, 2012·Bone Marrow Research·Elisa Dorantes-Acosta, Rosana Pelayo
Aug 11, 2012·Blood·Ursula CreutzigUNKNOWN AML Committee of the International BFM Study Group
Dec 18, 2014·Blood·Gert Ossenkoppele, Bob Löwenberg
Apr 9, 2015·Blood·Felicitas TholArnold Ganser
May 10, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Daniela F AngeliniFrancesco Lo-Coco
May 11, 2016·Current Opinion in Genetics & Development·Sheng LiAri Melnick
Jul 29, 2016·Journal of Hematology & Oncology·Adhra Al-MawaliIan Lewis
Aug 23, 2016·Nature Communications·Andrew L YoungTodd E Druley
Mar 10, 2017·Annals of Translational Medicine·A John Barrett
Mar 14, 2017·Current Treatment Options in Oncology·Prithviraj BoseJorge E Cortes
Jan 13, 2018·JCI Insight·Sonia GuedanCarl H June
Feb 6, 2018·Cell Stem Cell·Robert L BowmanRoss L Levine
Mar 21, 2018·Oncoscience·Maria De GrandisMichel Aurrand-Lions
Nov 7, 2018·Journal for Immunotherapy of Cancer·Regina JitschinDimitrios Mougiakakos
Nov 20, 2018·Cytometry. Part B, Clinical Cytometry·Anne E BrasVincent H J van der Velden
May 29, 2019·Experimental Hematology·Brett M StevensEnkhtsetseg Purev
Jun 20, 2019·International Journal of Molecular Sciences·Ramona RotoloDario Sangiolo

❮ Previous
Next ❯

Citations

Jan 9, 2021·Frontiers in Oncology·Scott R GoldsmithJohn F DiPersio
Sep 4, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Samanta Romina ZanettiPablo Menéndez
Jan 12, 2022·Current Opinion in Hematology·Jan KoedamGerhard Ehninger

❮ Previous
Next ❯

Methods Mentioned

BETA
xenograft
transfection
fluorescence-activated cell sorting
ELISA
FACS
Flow cytometry

Software Mentioned

FACSDiva

Related Concepts

Related Feeds

Cancer Immunotherapy

Cancer immunotherapy is an important field of research that is looking at controlling cancer and tumor growth by activating the individuals own immune system. Recent studies have utilized chimeric antigen receptor t-cell therapy, immune checkpoint inhibitors and neoantigen vaccines. Discover the latest research on cancer immunotherapy here.

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.

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.