Blockade of TGF-β and PD-L1 by bintrafusp alfa promotes survival in preclinical ovarian cancer models by promoting T effector and NK cell responses DOI Creative Commons

Jacob Kment,

Daniel Newsted,

Stephanie Young

et al.

British Journal of Cancer, Journal Year: 2024, Volume and Issue: 130(12), P. 2003 - 2015

Published: April 15, 2024

Abstract Background Failure of immunotherapy in high-grade serous ovarian cancer (HGSC) may be due to high levels transforming growth factor-β (TGF-β) ascites or tumour immune microenvironment (TIME). Here, we test whether coordinated blockade TGF-β and PD-L1 with bintrafusp alfa (BA) can provoke anti-tumour responses preclinical HGSC models. Methods BA is a first-in-class bifunctional inhibitor PD-L1, was tested for effects on overall survival altered TIME syngeneic Results Using mouse ID8-derived model IFNγ-inducible expression, treatments significantly reduced development burden. depleted VEGF ascites, skewed the towards cytotoxicity compared control. In BR5 model, increased tumour-infiltrating CD8 T cells effector memory cytotoxic markers, as well cytolytic NK cells. Extended produced ∼50% BA-cured mice that were protected from re-challenge. These had peritoneal T-effector controls. Conclusions Our studies advanced models support further testing an improved option patients cancer.

Language: Английский

Nivolumab plus ipilimumab combination therapy in cancer: Current evidence to date DOI

Marzieh Nikoo,

Fatemeh Rabiee,

Hossein Mohebbi

et al.

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 117, P. 109881 - 109881

Published: March 2, 2023

Language: Английский

Citations

17
Breaking Barriers: The Promise and Challenges of Immune Checkpoint Inhibitors in Triple-Negative Breast Cancer DOI Creative Commons

Sawsan Sudqi Said,

Wisam Nabeel Ibrahim

Biomedicines, Journal Year: 2024, Volume and Issue: 12(2), P. 369 - 369

Published: Feb. 5, 2024

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with pronounced immunogenicity, exhibiting rapid proliferation and immune cell infiltration into the tumor microenvironment. TNBC’s heterogeneity poses challenges to immunological treatments, inducing resistance mechanisms in Therapeutic modalities, including checkpoint inhibitors (ICIs) targeting PD-1, PD-L1, CTLA-4, are explored preclinical clinical trials. Promising results emerge from combining ICIs anti-TGF-β VISTA, hindering TNBC growth. cells employ complex evasion strategies involving interactions stromal cells, suppressing recognition through various cytokines, chemokines, metabolites. The recent focus on unraveling humoral cellular components aims disrupt crosstalk within This review identifies latest mechanisms, exploring potential targets for trials overcome enhance patient survival rates.

Language: Английский

Citations

8
Advances in reprogramming of energy metabolism in tumor T cells DOI Creative Commons

Liu Xuekai,

Yan Song, Jian Chu

et al.

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

Published: Feb. 13, 2024

Cancer is a leading cause of human death worldwide, and the modulation metabolic properties T cells employed in cancer immunotherapy holds great promise for combating cancer. As crucial factor, energy metabolism influences activation, proliferation, function cells, thus reprogramming unique research perspective immunology. Special conditions within tumor microenvironment high-energy demands lead to alterations cells. In-depth on can reveal mechanisms underlying immune tolerance provide important clues development new strategies as well. Therefore, study cell has clinical significance potential applications. In study, current achievements were reviewed. Then, influencing factors associated with introduced. addition, was summarized, which highlighted its enhancing therapeutic outcomes. summary, exhaustion leads functional exhaustion, resulting evasion by A better understanding may enable combat optimizing existing approaches.

Language: Английский

Citations

7
Oral probiotics microgel plus Galunisertib reduced TGF-β blockade resistance and enhanced anti-tumor immune responses in colorectal cancer DOI
Lili Niu, Yao Liu,

Nannan Li

et al.

International Journal of Pharmaceutics, Journal Year: 2024, Volume and Issue: 652, P. 123810 - 123810

Published: Jan. 18, 2024

Language: Английский

Citations

6
Blockade of TGF-β and PD-L1 by bintrafusp alfa promotes survival in preclinical ovarian cancer models by promoting T effector and NK cell responses DOI Creative Commons

Jacob Kment,

Daniel Newsted,

Stephanie Young

et al.

British Journal of Cancer, Journal Year: 2024, Volume and Issue: 130(12), P. 2003 - 2015

Published: April 15, 2024

Abstract Background Failure of immunotherapy in high-grade serous ovarian cancer (HGSC) may be due to high levels transforming growth factor-β (TGF-β) ascites or tumour immune microenvironment (TIME). Here, we test whether coordinated blockade TGF-β and PD-L1 with bintrafusp alfa (BA) can provoke anti-tumour responses preclinical HGSC models. Methods BA is a first-in-class bifunctional inhibitor PD-L1, was tested for effects on overall survival altered TIME syngeneic Results Using mouse ID8-derived model IFNγ-inducible expression, treatments significantly reduced development burden. depleted VEGF ascites, skewed the towards cytotoxicity compared control. In BR5 model, increased tumour-infiltrating CD8 T cells effector memory cytotoxic markers, as well cytolytic NK cells. Extended produced ∼50% BA-cured mice that were protected from re-challenge. These had peritoneal T-effector controls. Conclusions Our studies advanced models support further testing an improved option patients cancer.

Language: Английский

Citations

6