3D Microphysiological Tumor Model for Dual-Targeting CAR T Cell Immunotherapy DOI Open Access
Xuan Peng, Željko Janićijević, Liliana R. Loureiro

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 16, 2024

Abstract The efficiency of immunotherapy stays limited for solid tumors. It is mainly caused by the tumoral structural heterogeneity and its complex microenvironment, which impede infiltration immune cells into malignant tissues. Mimicking this environment in frames microphysiological models remains a challenge, significantly increasing costs clinical translation new therapies. Here, we study 3D multi-spheroid model incorporating prostate stem cell antigen (PSCA) modified PC3 human cancer fibroblast activation protein (FAP) expressing fibrosarcoma HT1080 embedded within soft hydrogel microbeads. We use to trial based on universal chimeric receptor (UniCAR) T cells, better understand impact FAP immunotherapeutic treatment First, demonstrate successful chemoattraction UniCAR area tumors, as well ability navigate through artificial extracellular matrix barriers. further observe synergistic efficacy dual-targeting approach against PSCA antigens, represent tumor microenvironment tumor, respectively. results our studies offer valuable methodologies insights engineering different studying immunotargeting small-sized tumors (e.g., metastases residual tumors). developed system has great potential advance research efforts aiming elucidate pivotal role development, enabling therapy trials more precise prognosis patients.

Language: Английский

Investigating the complex interplay between fibroblast activation protein α-positive cancer associated fibroblasts and the tumor microenvironment in the context of cancer immunotherapy DOI Creative Commons
Anton Kraxner, Franziska Braun, Wei‐Yi Cheng

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: July 5, 2024

Introduction This study investigates the role of Fibroblast Activation Protein (FAP)-positive cancer-associated fibroblasts (FAP+CAF) in shaping tumor immune microenvironment, focusing on its association with cell functionality and cytokine expression patterns. Methods Utilizing immunohistochemistry, we observed elevated FAP+CAF density metastatic versus primary renal carcinoma (RCC) tumors, higher correlating increased T infiltration RCC, a unique phenomenon illustrating complex interplay between progression, density, response. Results Analysis subsets FAP+CAF-rich stromal areas further revealed significant correlations FAP+ stroma various types, particularly RCC non-small lung cancer (NSCLC). was complemented by transcriptomic analyses, expanding range interrogated, as well to additional types. enabled evaluating these infiltration, vascularization other components microenvironment. Our comprehensive also encompassed cytokine, angiogenesis, inflammation gene signatures across different revealing heterogeneous cellular composition, expressions angiogenic profiles. Through pathway profiling, explored relationship states, uncovering potential immunosuppressive circuits that limit anti-tumor activity tumor-resident cells. Conclusions These findings underscore complexity biology necessity for personalized therapeutic patient enrichment approaches. The insights gathered from prevalence, provide valuable perspectives microenvironments, aiding future research clinical strategy development.

Language: Английский

Citations

3
3D Microphysiological Tumor Model for Dual-Targeting CAR T Cell Immunotherapy DOI Open Access
Xuan Peng, Željko Janićijević, Liliana R. Loureiro

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 16, 2024

Abstract The efficiency of immunotherapy stays limited for solid tumors. It is mainly caused by the tumoral structural heterogeneity and its complex microenvironment, which impede infiltration immune cells into malignant tissues. Mimicking this environment in frames microphysiological models remains a challenge, significantly increasing costs clinical translation new therapies. Here, we study 3D multi-spheroid model incorporating prostate stem cell antigen (PSCA) modified PC3 human cancer fibroblast activation protein (FAP) expressing fibrosarcoma HT1080 embedded within soft hydrogel microbeads. We use to trial based on universal chimeric receptor (UniCAR) T cells, better understand impact FAP immunotherapeutic treatment First, demonstrate successful chemoattraction UniCAR area tumors, as well ability navigate through artificial extracellular matrix barriers. further observe synergistic efficacy dual-targeting approach against PSCA antigens, represent tumor microenvironment tumor, respectively. results our studies offer valuable methodologies insights engineering different studying immunotargeting small-sized tumors (e.g., metastases residual tumors). developed system has great potential advance research efforts aiming elucidate pivotal role development, enabling therapy trials more precise prognosis patients.

Language: Английский

Citations

1