Immunotherapy for rapid bone marrow conditioning and leukemia depletion that allows efficient hematopoietic stem cell transplantation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F25%3A00642439" target="_blank" >RIV/68378050:_____/25:00642439 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/25:10499306

Výsledek na webu

<a href="https://doi.org/10.1136/jitc-2025-011888" target="_blank" >https://doi.org/10.1136/jitc-2025-011888</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1136/jitc-2025-011888" target="_blank" >10.1136/jitc-2025-011888</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Immunotherapy for rapid bone marrow conditioning and leukemia depletion that allows efficient hematopoietic stem cell transplantation

Popis výsledku v původním jazyce

Hematopoietic stem cell transplantation (HSCT) is a life-saving procedure to treat hematopoietic disorders. Current bone marrow conditioning protocols create space for healthy donor stem cells by employing irradiation and/or chemotherapy, but carry severe toxicities, resulting in significant morbidity, mortality and substantial long-term complications. To develop a low-toxicity solution, we generated a bi-specific T-cell engager (BTCE) that targets CD117, an abundantly expressed receptor on hematopoietic stem and progenitor cells (HSPC) and leukemia-initiating cells (LICs). We show that the CD117xCD3 BTCE efficiently depletes in vitro and in vivo HSPCs and LICs. The CD117xCD3 BTCE was not toxic and facilitates highly efficient engraftment of human allogenic donor CD34+cells in humanized mice, thereby restoring hematopoiesis in vivo in both normal and leukemia-bearing humanized mice. We demonstrate here that a potent CD117xCD3 BTCE enables rapid HSCT in both benign and malignant conditions.

Název v anglickém jazyce

Immunotherapy for rapid bone marrow conditioning and leukemia depletion that allows efficient hematopoietic stem cell transplantation

Popis výsledku anglicky

Hematopoietic stem cell transplantation (HSCT) is a life-saving procedure to treat hematopoietic disorders. Current bone marrow conditioning protocols create space for healthy donor stem cells by employing irradiation and/or chemotherapy, but carry severe toxicities, resulting in significant morbidity, mortality and substantial long-term complications. To develop a low-toxicity solution, we generated a bi-specific T-cell engager (BTCE) that targets CD117, an abundantly expressed receptor on hematopoietic stem and progenitor cells (HSPC) and leukemia-initiating cells (LICs). We show that the CD117xCD3 BTCE efficiently depletes in vitro and in vivo HSPCs and LICs. The CD117xCD3 BTCE was not toxic and facilitates highly efficient engraftment of human allogenic donor CD34+cells in humanized mice, thereby restoring hematopoiesis in vivo in both normal and leukemia-bearing humanized mice. We demonstrate here that a potent CD117xCD3 BTCE enables rapid HSCT in both benign and malignant conditions.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

<a href="/cs/project/LX22NPO5102" target="_blank" >LX22NPO5102: Národní ústav pro výzkum rakoviny</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal for ImmunoTherapy of Cancer

ISSN

2051-1426

e-ISSN

2051-1426

Svazek periodika

13

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

13

Strana od-do

e011888

Kód UT WoS článku

001519647600001

EID výsledku v databázi Scopus

2-s2.0-105009640028