Specific antitumor activity of anti-CA125 CAR-T lymphocytes against CA125-positive and CA125-negative cells DOI Creative Commons
Т М Кулинич, Y.Y. Kiseleva, A. M. Shishkin

et al.

Sechenov Medical Journal, Journal Year: 2024, Volume and Issue: 15(2), P. 36 - 47

Published: July 31, 2024

Aim. To evaluate the antitumor efficacy of our developed drug based on cytotoxic T lymphocytes genetically modified with a chimeric antigen receptor (CAR) specific to CA125 in relation both CA125-positive and CA125negative cell cultures. Materials methods. We performed an vitro study human ovarian cancer cells (OVCAR-3, OVKATE) negative (breast MCF 7, embryonic kidney HEK293). Cytotoxic effects tumor were evaluated after 0, 4, 8 24 hours using 3’-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) Lactate Dehydrogenase (LDH) tests. also studied changes number “in real time” when exposed transfected RTCA iCELLIgence device (ACEA Biosciences, USA). Lymphokineactivated killer (LAK) used as specificity control. Results. The demonstrated that anti-CA125 CAR-T exhibited pronounced effect OVCAR-3 OVKATE cultures, exceeding LAK by 1.3 times. population experimental samples decreased 70 ± 4%, which exceeded 9 8.2%. With regard MCF-7 line, was minimal evidenced 25.8% decrease relative live comparison cytotoxicity 68%. Real-time monitoring proliferation viability proved high against cultures expressing CA-125, while inferior not (MCF-7, Conclusions. use lines LAK, achieved CA125-negative HEK293 cells.

Language: Английский

Nanotechnology for boosting ovarian cancer immunotherapy DOI Creative Commons
Prabhjot Kaur, Santosh Kumar Singh, Manoj K. Mishra

et al.

Journal of Ovarian Research, Journal Year: 2024, Volume and Issue: 17(1)

Published: Oct. 14, 2024

Ovarian cancer, often referred to as the "silent killer," is notoriously difficult detect in its early stages, leading a poor prognosis for many patients. Diagnosis delayed until cancer has advanced, primarily due ambiguous and frequently occurring clinical symptoms. leads more deaths than any other of female reproductive system. The main reasons high mortality rates include diagnosis resistance treatment. As result, there an urgent need improved diagnostic treatment options ovarian cancer. standard treatments typically involve debulking surgery along with platinum-based chemotherapies. Among patients advanced-stage who initially respond current therapies, 50-75% experience recurrence. Recently, immunotherapy-based approaches enhance body's immune response combat tumor growth have shown promise. Immune checkpoint inhibitors promising results treating types tumors. However, only few these been effective because tumor's environment suppresses system creates barriers This hampers effectiveness existing immunotherapies. Nonetheless, advanced immunotherapy techniques delivery systems based on nanotechnology hold promise overcoming challenges.

Language: Английский

Citations

6
Enhancing the Antitumor Effect of MUC16 CART Cells in Ovarian Cancer: The Potential of Oncolytic Adenovirus DOI

Qiuman Wang,

Wofeng Liu,

Yuanchun Fan

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217588 - 217588

Published: Feb. 1, 2025

Language: Английский

Citations

0
Mesothelin as a Signal Pathways and Epigenetic Target in Cancer Therapy DOI Open Access
Seema Kumari

Cancers, Journal Year: 2025, Volume and Issue: 17(7), P. 1118 - 1118

Published: March 26, 2025

Mesothelin (MSLN), a glycoprotein-based tumor antigen, is elevated in several malignancies and it related to poor prognosis, as enhances aggression, dissemination chemotherapy resistance. MSLN plays crucial role epigenetic signal pathway regulation can be an important biomarker. targeting particular, associated with CA125/MUC16, which offers the potential improve lung, pancreatic, colon ovarian cancer detection well therapeutic strategies. MSLNtargeted therapies have shown favorable results, such CAR NK cells, 227Th conjugate CAR-T target mesothelin. Significant advancements achieved novel techniques, mesothelin-targeting BiTEs simultaneous cells. Immunotherapies mesothelin completely transform way therapy patients limited options. To fully comprehend mechanisms of MSLN, more investigation required explore its for improved patient outcomes. The complex control, cellular functions clinical significance advancement are highlighted this review.

Language: Английский

Citations

0
Ecological and evolutionary dynamics to design and improve ovarian cancer treatment DOI Creative Commons
Grace Han, Monica Alexander,

Julia Gattozzi

et al.

Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(9)

Published: Aug. 29, 2024

Ovarian cancer ecosystems are exceedingly complex, consisting of a high heterogeneity cells. Development drugs such as poly ADP-ribose polymerase (PARP) inhibitors, targeted therapies and immunotherapies offer more options for sequential or combined treatments. Nevertheless, mortality in metastatic ovarian patients remains because cells consistently develop resistance to single combination therapies, urging need treatment designs that target the evolvability The evolutionary dynamics lead emerge from complex tumour microenvironment, heterogeneous populations, individual cell's plasticity. We propose successful management requires consideration ecological disease. Here, we review current challenges discuss principles evolution. conclude by proposing evolutionarily designed strategies cancer, with goal integrating longitudinal, quantitative data improve design drug resistance. KEY POINTS/HIGHLIGHTS: Tumours which non-cancer interact evolve dynamic ways. Conventional inevitably development they fail consider tumours' cellular Eco-evolutionarily should cell plasticity patient-specific characteristics clinical outcome prevent relapse.

Language: Английский

Citations

3
Advancing biliary tract malignancy treatment: emerging frontiers in cell-based therapies DOI Creative Commons

Jian‐Yang Ao,

Mingtai Hu,

Jinghan Wang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 12, 2025

Biliary tract malignancies, including intrahepatic cholangiocarcinoma, extrahepatic and gallbladder cancer, represent a group of aggressive cancers with poor prognosis due to late-stage diagnosis, limited treatment options, resistance conventional therapies like chemotherapy radiotherapy. These challenges emphasize the urgent need for innovative therapeutic approaches. In recent years, cell-based have emerged as promising avenue, offering potential solutions through immune modulation, genetic engineering, targeted intervention in tumor microenvironment. This Mini-review provides an overview current advancements biliary encompassing strategies such CAR-T cells, NK dendritic cell vaccines, tumor-infiltrating lymphocytes. We also examine overcome immunosuppressive microenvironment discuss integration into multimodal regimens. By synthesizing preclinical clinical findings, this review highlights key insights future directions, aiming assist researchers clinicians translating these approaches effective treatments. The transformative discussed here makes valuable resource advancing malignancy research applications.

Language: Английский

Citations

0
Transforming treatment paradigms: Focus on personalized medicine for high‐grade serous ovarian cancer DOI Open Access
Paweł Kordowitzki,

Britta Lange,

Kevin M. Elias

et al.

CA A Cancer Journal for Clinicians, Journal Year: 2025, Volume and Issue: unknown

Published: April 19, 2025

Abstract High‐grade serous ovarian cancer (HGSOC) is the most common and aggressive subtype of cancer, accounting for approximately 70% all cases contributing significantly to high mortality rates associated with this disease. Because asymptomatic nature early stage disease, patients are diagnosed at advanced stages when has already spread into abdominal cavity, requiring complex intensive surgical chemotherapeutic interventions followed by maintenance therapies. Although a minority well defined genetic syndromes, specific risk factors clear etiology in many remain elusive. HGSOC tumors characterized frequency somatic gene copy number alterations, often defects homologous recombination repair DNA. All attempts introduce an effective screening date have been unsuccessful. This review elucidates complexities surrounding encompasses its etiology, epidemiology, classification, pathogenesis, current array treatment strategies. Understanding molecular underpinnings crucial development targeted therapies personalized multimodal approaches centralized therapeutic structures. also examines importance tumor microenvironment. In addition, authors' objective underscore critical placing patient's perspective diversity forefront strategies, thereby fostering genuinely participatory decision‐making process ultimately improving patient quality life.

Language: Английский

Citations

0
Targeting Cancer Stem Cells with Radioimmunotherapy: The Case of the Ovarian Cancer Stemness-Associated Biomarker L1CAM DOI Creative Commons

Tihomir Zh. Todorov,

Roger Schibli, Martin Béhé

et al.

International Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 4(3), P. 463 - 485

Published: July 18, 2024

Cancer stem cells (CSCs) are a dynamic population of tumor characterized by long-term self-renewal, high tumorigenicity, resistance to conventional therapies such as radio- and chemotherapy, capacity recapitulate the heterogeneity. Similar other cells, CSCs need carry critical mutations epigenetic changes acquire their aberrant phenotype. Confirmed in various hematologic solid malignancies, deepen our understanding CSC biology, including identification biomarkers, develop novel CSC-targeted has been clearly recognized. Here, we review L1 cell adhesion molecule (L1CAM) CSC-associated biomarker ovarian cancer. Furthermore, inform on promising potential anti-L1CAM radioimmunotherapy with 161Tb therapeutic approach overcome radioresistance comparison 177Lu.

Language: Английский

Citations

2
Specific antitumor activity of anti-CA125 CAR-T lymphocytes against CA125-positive and CA125-negative cells DOI Creative Commons
Т М Кулинич, Y.Y. Kiseleva, A. M. Shishkin

et al.

Sechenov Medical Journal, Journal Year: 2024, Volume and Issue: 15(2), P. 36 - 47

Published: July 31, 2024

Aim. To evaluate the antitumor efficacy of our developed drug based on cytotoxic T lymphocytes genetically modified with a chimeric antigen receptor (CAR) specific to CA125 in relation both CA125-positive and CA125negative cell cultures. Materials methods. We performed an vitro study human ovarian cancer cells (OVCAR-3, OVKATE) negative (breast MCF 7, embryonic kidney HEK293). Cytotoxic effects tumor were evaluated after 0, 4, 8 24 hours using 3’-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) Lactate Dehydrogenase (LDH) tests. also studied changes number “in real time” when exposed transfected RTCA iCELLIgence device (ACEA Biosciences, USA). Lymphokineactivated killer (LAK) used as specificity control. Results. The demonstrated that anti-CA125 CAR-T exhibited pronounced effect OVCAR-3 OVKATE cultures, exceeding LAK by 1.3 times. population experimental samples decreased 70 ± 4%, which exceeded 9 8.2%. With regard MCF-7 line, was minimal evidenced 25.8% decrease relative live comparison cytotoxicity 68%. Real-time monitoring proliferation viability proved high against cultures expressing CA-125, while inferior not (MCF-7, Conclusions. use lines LAK, achieved CA125-negative HEK293 cells.

Language: Английский

Citations

0