CAR-T Cell Therapy: The Limitation and Solution DOI

S Y Wang

Highlights in Science Engineering and Technology, Journal Year: 2024, Volume and Issue: 102, P. 444 - 450

Published: July 11, 2024

Driven by breakthroughs in biomedical research, chimeric antigen receptor (CAR) T cell therapy has been a potential new class of the that is now being explored field biology with regard to cancer treatment.These genetically engineered immune cells are designed selectively target antigens expressed on tumour cells, presenting novel avenue immunotherapy. Particularly liquid tumours such as acute lymphoblastic leukaemia (ALL), noteworthy therapeutic performance CAR-T highlights their promise treatment research.Nevertheless, despite remarkable achievements, considerable challenges persist. Issues an immunosuppressive microenvironment (TME), loss, and restricted trafficking, especially solid tumours, present formidable obstacles. Researchers have proposed strategies aimed at surmounting these challenges, including dual-targeted design TME modification, which offer promising avenues for advancement. However, unresolved questions linger, emphasizing ongoing need innovative solutions.

Language: Английский

Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition DOI Creative Commons
Antonino Glaviano,

Hannah Lau,

Lukas M. Carter

et al.

Journal of Hematology & Oncology, Journal Year: 2025, Volume and Issue: 18(1)

Published: Jan. 13, 2025

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, signaling molecules that interact promote growth therapeutic resistance. Elucidating the intricate interactions between cells TME crucial in understanding progression challenges. A critical process induced by epithelial-mesenchymal transition (EMT), wherein epithelial acquire mesenchymal traits, which enhance their motility invasiveness progression. By targeting various components TME, novel investigational strategies aim disrupt TME's contribution EMT, thereby improving efficacy, addressing resistance, offering a nuanced approach therapy. This review scrutinizes key players emphasizing avenues therapeutically components. Moreover, article discusses implications for resistance mechanisms highlights current toward modulation along with potential caveats.

Language: Английский

Citations

16
Chimeric Antigen Receptor (CAR) T-Cell Therapy in Hematologic Malignancies: Clinical Implications and Limitations DOI Open Access
Philipp Blüm, Sabine Käyser

Cancers, Journal Year: 2024, Volume and Issue: 16(8), P. 1599 - 1599

Published: April 22, 2024

Chimeric antigen receptor (CAR) T-cell therapy has become a powerful treatment option in B-cell and plasma cell malignancies, many patients have benefited from its use. To date, six CAR products been approved by the FDA EMA, more are being developed investigated clinical trials. The whole field of adoptive transfer experienced an unbelievable development process, we now at edge new era immune therapies that will impact beyond hematologic malignancies. Areas interest are, e.g., solid oncology, autoimmune diseases, infectious others. Although much achieved so far, there is still huge effort needed to overcome significant challenges difficulties. We witnessing rapid expansion knowledge, induced biomedical technologies designs. just begun, widen therapeutic landscape future. This review provides comprehensive overview applications T-cells, focusing on emphasizing their benefits but also indicating limitations challenges.

Language: Английский

Citations

10
How the Western Diet Thwarts the Epigenetic Efforts of Gut Microbes in Ulcerative Colitis and Its Association with Colorectal Cancer DOI Creative Commons
Avisek Majumder,

Shabana Bano

Biomolecules, Journal Year: 2024, Volume and Issue: 14(6), P. 633 - 633

Published: May 29, 2024

Ulcerative colitis (UC) is an autoimmune disease in which the immune system attacks colon, leading to ulcer development, loss of colon function, and bloody diarrhea. The human gut ecosystem consists almost 2000 different species bacteria, forming a bioreactor fueled by dietary micronutrients produce bioreactive compounds, are absorbed our body signal distant organs. Studies have shown that Western diet, with fewer short-chain fatty acids (SCFAs), can alter microbiome composition cause host's epigenetic reprogramming. Additionally, overproduction H

Language: Английский

Citations

5
Targeting refractory diffuse large B cell lymphoma by CAR-WEE1 T-cells: In vitro evaluation DOI Creative Commons

Hadeer Mohamed Ahmed,

Said S. Moselhy, Magda I. Mohamad

et al.

Annals of Hematology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Abstract Refractory Diffuse Large B-cell Lymphoma (DLBCL) presents a major therapeutic challenge due to its resistance standard treatments. Engineered T-cells, especially Chimeric Antigen Receptor (CAR) have shown promise in overcoming drug resistance. This study investigates the effectiveness of WEE1-engineered T-cells targeting and eliminating refractory DLBCL vitro. CAR were created by transducing 5th-generation construct designed recognize WEE1, surface antigen commonly found on cells. The cytotoxic effect engineered was tested against Rituximab-resistant cells (RR-NU-DUL-1). Apoptosis cell cycle evaluated using flow cytometry. Quantitative Real-time PCR (RT-PCR) used measure expression BCL2, CDK2. results showed significant increase target lysis, apoptosis, necrosis, reduction percentage G2M phase cycle, as well decrease gene level, indicating strong anti-tumor activity. These findings suggest that T-cell therapy holds great for treating DLBCL, offering potential path clinical application. vitro evaluation highlights targeted treatment strategy emphasizing their applicability ability overcome mechanisms this aggressive lymphoma subtype.

Language: Английский

Citations

0
Selective JAK2 pathway inhibition enhances anti-leukemic functionality in CD19 CAR-T cells DOI Creative Commons

Kohei Mitsuno,

Masaya Suematsu, Yuki Naito

et al.

Cancer Immunology Immunotherapy, Journal Year: 2025, Volume and Issue: 74(3)

Published: Feb. 1, 2025

Language: Английский

Citations

0
Targeting the Immune Microenvironment in Chronic Lymphocytic Leukemia: An Evolving Therapeutic Strategy DOI Open Access
Clement Chung,

Duc Hoang Doan

European Journal Of Haematology, Journal Year: 2025, Volume and Issue: unknown

Published: March 11, 2025

ABSTRACT Although small molecule inhibitors that target the aberrant signaling pathways and molecular defects of chronic lymphocytic leukemia (CLL) result in improved survival benefits vs. traditional chemoimmunotherapy or chemotherapy, treatment resistance may later, reflecting intrinsic tumor heterogeneity, persistence leukemic clone, presence microenvironment, which supports disease clone. Patients with CLL have immune‐related abnormalities T lymphocyte subset composition, immune synapse formation, other dysregulations. Cellular interactions between clone its microenvironment provide therapeutic opportunities to these pathogenesis pathways, potentially improving patient's functions clinical outcomes targeted therapies. At present, despite lack response checkpoint CLL, they showed promising efficacy patients Richter transformation. Together CD19‐targeted chimeric antigen receptor–modified cell (CAR‐T) therapy, novel bispecific antibodies immunotherapies are being investigated improve for relapsed refractory (R/R) as exemplified by epcoritamab, a antibody recently demonstrated initial R/R high‐risk subgroups, including those TP53 aberrations unmutated genes encode immunoglobulin variable heavy chain region ( IGHV ). Furthermore, address escape cancer cells issues impact durability single‐targeted cell‐redirected therapies, strategies such trispecific combination therapies increase specificity activation. In summary, there is emerging evidence counteract immunosuppressive responses, decrease risk infection, overcome resistance.

Language: Английский

Citations

0
A Comprehensive Review About the Use of Monoclonal Antibodies in Cancer Therapy DOI Creative Commons
Angel A Justiz-Vaillant, Bijay Raj Pandit, Chandrashekhar Unakal

et al.

Antibodies, Journal Year: 2025, Volume and Issue: 14(2), P. 35 - 35

Published: April 11, 2025

Monoclonal antibodies (mAbs) targeting various pathways in cancer therapy play crucial roles enhancing the immune system's ability to recognise and eliminate tumour cells. These therapies are designed either block inhibitory checkpoint or target specific cell markers for direct destruction. Additionally, mAbs can modulate microenvironment, enhance antibody-dependent cellular cytotoxicity, inhibit angiogenesis, further amplifying their therapeutic impact. Below is a summary of monoclonal key pathways, along with indications mechanisms action, which reviewed based on mechanisms.

Language: Английский

Citations

0
State of the art in CAR-based therapy: In vivo CAR production as a revolution in cell-based cancer treatment DOI Creative Commons
Abdolreza Esmaeilzadeh, Kaveh Hadiloo,

Sara Yaghoubi

et al.

Cellular Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Chimeric antigen receptor (CAR) therapy has successfully treated relapsed/refractory hematological cancers. This strategy can effectively target tumor cells. However, despite positive outcomes in clinical applications, challenges remain to overcome. These hurdles pertain the production of drugs, solid resistance, and side effects related treatment. Some cases have been missed during drug preparation due manufacturing issues, prolonged times, high costs. mainly arise from vitro process, so reevaluating this process could minimize number patients. The immune cells are traditionally collected sent laboratory; after several steps, modified express CAR gene before being injected back into patient's body. During vivo method, is introduced inside allows for treatment begin sooner, avoiding potential failures associated In review, we will elaborate on using CAR, examine benefits approach, ultimately present available solutions incorporating practice.

Language: Английский

Citations

0
Deciphering the Potentials of Cardamom in Cancer Prevention and Therapy: From Kitchen to Clinic DOI Creative Commons

Shabana Bano,

Avisek Majumder, Ayush Srivastava

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(9), P. 1166 - 1166

Published: Sept. 18, 2024

Cardamom (cardamum) is a spice produced from the seeds of several Elettaria and Amomum plants Zingiberaceae family. has been demonstrated to offer numerous benefits, including its antioxidant, antimicrobial, anti-inflammatory, other metabolic (anti-diabetic) properties, potential reduce cancer risk. Recently, researchers have extracted tested multiple phytochemicals cardamom assess their effectiveness against various types human malignancy. These studies indicated that can help overcome drug resistance standard chemotherapy protect chemotherapy-induced toxicity due scavenging properties. Furthermore, chemical compounds in cardamom, limonene, cymene, pinene, linalool, borneol, cardamonin, indole-3-carbinol, diindolylmethane, primarily target programmed cell death lignin-1 gene, which more prevalent cells than healthy cells. This review provides medicinal properties pharmacological uses cellular effects, therapeutic prevention treatment, as well use reducing improving overall health patients. Based on previous preclinical studies, shows significant an anti-cancer agent, but further exploration for clinical warranted diverse mechanisms action.

Language: Английский

Citations

3
Design and development of dual targeting CAR protein for the development of CAR T-cell therapy against KRAS mutated pancreatic ductal adenocarcinoma using computational approaches DOI Creative Commons
Prasanna Srinivasan Ramalingam,

T. Premkumar,

Vino Sundararajan

et al.

Discover Oncology, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 25, 2024

Mutant KRAS promotes the proliferation, metastasis, and aggressiveness of various cancers including pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), colorectal (CRC) respectively. therapeutics are limited, while Sotorasib Adagrasib were only FDA-approved drugs for treatment

Language: Английский

Citations

3