Neoadjuvant intratumoral MBT(A) immunotherapy prevents distant metastases and recurrence in murine models

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12310%2F25%3A43909990" target="_blank" >RIV/60076658:12310/25:43909990 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/25:00140710 RIV/00216208:11110/25:10492817

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S030438352500028X?pes=vor&utm_source=clarivate&getft_integrator=clarivate" target="_blank" >https://www.sciencedirect.com/science/article/pii/S030438352500028X?pes=vor&utm_source=clarivate&getft_integrator=clarivate</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.canlet.2025.217464" target="_blank" >10.1016/j.canlet.2025.217464</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Neoadjuvant intratumoral MBT(A) immunotherapy prevents distant metastases and recurrence in murine models

Popis výsledku v původním jazyce

Neoadjuvant immunotherapy represents a pioneering approach in the preoperative treatment of cancer, providing new strategies for tumor reduction and improved patient outcomes by modulating the immune response. This study investigated neoadjuvant immunotherapy using intratumoral administration of mannanBAM, Toll-like receptor ligands, and anti-CD40 antibody (MBTA therapy) followed by surgery in murine models of MTT pheochromocytoma, B16-F10 melanoma, and 4T1 and E0771.lmb mammary carcinomas. In the MTT pheochromocytoma model, it was found that neoadjuvant MBTA therapy followed by surgery could prevent the development of distant metastases in 100% of treated animals, compared to a 60% mortality rate in the control group due to metastatic disease after surgery. These outcomes were achieved even in tumors three times larger than those in the control group. In the aggressive 4T1 model, neoadjuvant MBTA therapy resulted in slower tumor progression and a significant prolongation of survival. In the B16-F10 and E0771.lmb models, neoadjuvant MBTA therapy also protected animals from metastases development and tumor recurrence upon rechallenge with tumor cells after surgery. Transcriptomic analysis revealed enhanced effector immune cell infiltration, cytotoxicity, and antigen presentation in retransplanted tumors from MBTA-treated mice, indicating robust immune memory. Notably, the exclusion of the anti-CD40 antibody from the neoadjuvant MBTA therapy (MBT therapy) yielded comparable outcomes in protection against metastases development. These findings advocate for further investigation of intratumoral neoadjuvant MBTA therapy for immunologically &quot;cold&quot; tumors, including those at high risk of metastases or recurrence.

Název v anglickém jazyce

Neoadjuvant intratumoral MBT(A) immunotherapy prevents distant metastases and recurrence in murine models

Popis výsledku anglicky

Neoadjuvant immunotherapy represents a pioneering approach in the preoperative treatment of cancer, providing new strategies for tumor reduction and improved patient outcomes by modulating the immune response. This study investigated neoadjuvant immunotherapy using intratumoral administration of mannanBAM, Toll-like receptor ligands, and anti-CD40 antibody (MBTA therapy) followed by surgery in murine models of MTT pheochromocytoma, B16-F10 melanoma, and 4T1 and E0771.lmb mammary carcinomas. In the MTT pheochromocytoma model, it was found that neoadjuvant MBTA therapy followed by surgery could prevent the development of distant metastases in 100% of treated animals, compared to a 60% mortality rate in the control group due to metastatic disease after surgery. These outcomes were achieved even in tumors three times larger than those in the control group. In the aggressive 4T1 model, neoadjuvant MBTA therapy resulted in slower tumor progression and a significant prolongation of survival. In the B16-F10 and E0771.lmb models, neoadjuvant MBTA therapy also protected animals from metastases development and tumor recurrence upon rechallenge with tumor cells after surgery. Transcriptomic analysis revealed enhanced effector immune cell infiltration, cytotoxicity, and antigen presentation in retransplanted tumors from MBTA-treated mice, indicating robust immune memory. Notably, the exclusion of the anti-CD40 antibody from the neoadjuvant MBTA therapy (MBT therapy) yielded comparable outcomes in protection against metastases development. These findings advocate for further investigation of intratumoral neoadjuvant MBTA therapy for immunologically &quot;cold&quot; tumors, including those at high risk of metastases or recurrence.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

<a href="/cs/project/LUAUS24120" target="_blank" >LUAUS24120: Synergické cílení klíčových znaků nádorových buněk a jejich mikroprostředí</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

CANCER LETTERS

ISSN

0304-3835

e-ISSN

1872-7980

Svazek periodika

612

Číslo periodika v rámci svazku

MAR 1 2025

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

12

Strana od-do

nestránkováno

Kód UT WoS článku

001409741500001

EID výsledku v databázi Scopus

2-s2.0-85215826301