Cyclooxygenase-2-Prostaglandin E2 pathway: A key player in tumor-associated immune cells DOI Creative Commons

Kaipeng Jin,

Chao Qian, Jinti Lin

et al.

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: Jan. 27, 2023

Cyclooxygenases-2 (COX-2) and Prostaglandin E2 (PGE2), which are important in chronic inflammatory diseases, can increase tumor incidence promote growth metastasis. PGE2 binds to various prostaglandin E receptors activate specific downstream signaling pathways such as PKA pathway, β-catenin NF-κB pathway PI3K/AKT all of play roles biological pathological behavior. Nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors, EP antagonists anti-tumor immune evasion. The COX-2-PGE2 promotes evasion by regulating myeloid-derived suppressor cells, lymphocytes (CD8+ T CD4+ cells natural killer cells), antigen presenting (macrophages dendritic cells). Based on conventional treatment, the addition inhibitors or may enhance immunotherapy response escape. However, there still a lot challenges cancer immunotherapy. In this review, we focus how affects tumor-associated cells.

Language: Английский

Drug discovery is an eternal challenge for the biomedical sciences DOI Creative Commons
Hua Li, Wenyi Wei, Hong‐Xi Xu

et al.

Acta Materia Medica, Journal Year: 2022, Volume and Issue: 1(1)

Published: Jan. 1, 2022

In this inaugural Editorial the Co-Editors-in-Chief and Executive Editor of Acta Materia Medica Hua Li Wenyi Wei Hongxi Xu discuss how drug discovery is an eternal challenge for biomedical sciences. The new drugs among humanity’s most sophisticated cutting-edge intellectual activities. This process requires not only […]

Language: Английский

Citations

103
Harnessing the potential of CAR-T cell therapy: progress, challenges, and future directions in hematological and solid tumor treatments DOI Creative Commons

Gunjan Dagar,

Ashna Gupta,

Tariq Masoodi

et al.

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: July 7, 2023

Abstract Traditional cancer treatments use nonspecific drugs and monoclonal antibodies to target tumor cells. Chimeric antigen receptor (CAR)-T cell therapy, however, leverages the immune system's T-cells recognize attack are isolated from patients modified tumor-associated antigens. CAR-T therapy has achieved FDA approval for treating blood cancers like B-cell acute lymphoblastic leukemia, large lymphoma, multiple myeloma by targeting CD-19 maturation Bi-specific chimeric receptors may contribute mitigating escape, but their efficacy could be limited in cases where certain cells do not express targeted Despite success cancers, technology faces challenges solid tumors, including lack of reliable antigens, hypoxic cores, immunosuppressive environments, enhanced reactive oxygen species, decreased T-cell infiltration. To overcome these challenges, current research aims identify antigens develop cost-effective, microenvironment-specific This review covers evolution against various hematological highlights faced suggests strategies obstacles, such as utilizing single-cell RNA sequencing artificial intelligence optimize clinical-grade

Language: Английский

Citations

102
Unveiling the mechanisms and challenges of cancer drug resistance DOI Creative Commons
Sameer Ullah Khan, Kaneez Fatima,

Shariqa Aisha

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 12, 2024

Abstract Cancer treatment faces many hurdles and resistance is one among them. Anti-cancer strategies are evolving due to innate acquired capacity, governed by genetic, epigenetic, proteomic, metabolic, or microenvironmental cues that ultimately enable selected cancer cells survive progress under unfavorable conditions. Although the mechanism of drug being widely studied generate new target-based drugs with better potency than existing ones. However, broader flexibility in resistance, advanced therapeutic options efficacy need be explored. Combination therapy an alternative a success rate though risk amplified side effects commonplace. Moreover, recent groundbreaking precision immune ways overcome has revolutionized anticancer greater extent only limitation individual-specific needs further attention. This review will focus on challenges opted withstand current therapies at molecular level also highlights emerging -like immunological, stem cell-based may prove have potential challenge problem resistance.

Language: Английский

Citations

101
Cancer treatments: Past, present, and future DOI
Dmitriy Sonkin, Anish Thomas, Beverly A. Teicher

et al.

Cancer Genetics, Journal Year: 2024, Volume and Issue: 286-287, P. 18 - 24

Published: June 17, 2024

Language: Английский

Citations

98
Pharmacotherapy of Generalized Myasthenia Gravis with Special Emphasis on Newer Biologicals DOI Open Access
Deepak Menon, Vera Bril

Drugs, Journal Year: 2022, Volume and Issue: 82(8), P. 865 - 887

Published: May 31, 2022

Language: Английский

Citations

88
Recent Progress and Future Perspectives of Immunotherapy in Advanced Gastric Cancer DOI Creative Commons
Xin Jin, Zhaorui Liu,

Dongxiao Yang

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: July 1, 2022

As one of the most common forms solid tumours, gastric carcinoma has been revealed as third leading cause death worldwide. The symptom cancer is usually not obvious and thus difficult to detect at earlier stages. Therefore, already in advanced stage once detected patients, which a poor prognosis due ineffective therapies multiple resistance. Recent advance understanding microenvironment significantly promoted development immunotherapy for cancer. Immunotherapy can induce immune responses patients leads destruction cells. In comparison traditional therapy, demonstrated robust efficacy tolerable toxicity. this novel strategy treatment gain increasingly popularity. review, we summarize recent progress cancer, such check point inhibitors, adoptive cell VEGF vaccines CAR-T therapy. We highlight immunotherapies involved clinical applications discuss existing challenges current promising strategies overcome these limitations.

Language: Английский

Citations

88
Immunosuppression in tumor immune microenvironment and its optimization from CAR-T cell therapy DOI Creative Commons

Zaoqu Liu,

Zhaokai Zhou, Qin Dang

et al.

Theranostics, Journal Year: 2022, Volume and Issue: 12(14), P. 6273 - 6290

Published: Jan. 1, 2022

Chimeric antigen receptor (CAR)-T cell therapy represents a landmark advance in personalized cancer treatment.CAR-T strategy generally engineers T cells from specific patient with new antigen-specificity, which has achieved considerable success hematological malignancies, but scarce benefits solid tumors.Recent studies have demonstrated that tumor immune microenvironment (TIME) cast profound impact on the immunotherapeutic response.The immunosuppressive landscape of TIME is critical obstacle to effector activity CAR-T cells.Nevertheless, every cloud silver lining.The components also shed inspiration reshaping friendly by targeting them engineered CARs.Herein, we summarize recent advances disincentives and discuss approaches technologies enhance efficacy via addressing current hindrances.Simultaneously, firmly believe parsing TIME, rationally manipulating complex interactions components, optimizing for each patient, immunotherapy responsiveness malignancies will be substantially enhanced, novel therapeutic targets revealed.

Language: Английский

Citations

87
Next generations of CAR-T cells - new therapeutic opportunities in hematology? DOI Creative Commons
Jaromir Tomasik, Marcin Jasiński, Grzegorz Basak

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 28, 2022

In recent years, the introduction of chimeric antigen receptor (CAR) T-cell therapies into clinics has been a breakthrough in treating relapsed or refractory malignancies hematology and oncology. To date, Food Drug Administration (FDA) approved six CAR-T for specific non-Hodgkin lymphomas, B-cell acute lymphoblastic leukemia, multiple myeloma. All registered treatments most clinical trials are based on so-called 2nd generation CARs, which consist an extracellular antigen-binding region, one costimulatory domain, CD3z signaling domain. Unfortunately, despite remarkable overall treatment outcomes, relatively high percentage patients do not benefit from therapy (overall response rate varies between 50 100%, with following relapse rates as 66% due to limited durability response). Moreover, it is associated adverse effects such cytokine release syndrome neurotoxicity. Advances immunology molecular engineering have facilitated construction next cells equipped various mechanisms. These include additional domains (3rd generation), safety switches, immune-checkpoint modulation, expression, knockout therapy-interfering molecules, name just few. Implementation next-generation CAR T-cells may allow overcoming current limitations therapies, decreasing unwanted side effects, targeting other hematological malignancies. Accordingly, some currently evaluating efficacy novel therapies. This review describes cell constructs concerning application, summarizes completed ongoing presents future perspectives.

Language: Английский

Citations

87
iPSC-Derived Natural Killer Cell Therapies - Expansion and Targeting DOI Creative Commons
Benjamin Goldenson, Pooja Hor, Dan S. Kaufman

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Feb. 3, 2022

Treatment of cancer with allogeneic natural killer (NK) cell therapies has seen rapid development, especially use against hematologic malignancies. Clinical trials NK cell-based adoptive transfer to treat relapsed or refractory malignancies have used peripheral blood, umbilical cord blood and pluripotent stem cell-derived cells, each approach undergoing continued clinical development. Improving the potency these relies on genetic modifications improve tumor targeting enhance expansion persistence cells. Induced (iPSC)-derived cells allow for routine targeted introduction resulting derived from a clonal starting population. In this review, we discuss summarize recent important advances in development new iPSC-derived therapies, focus improved cancer. We then improvements methods expand how iPSC-NK can be enhanced. Finally, describe may combine future therapy products treatment both solid tumors.

Language: Английский

Citations

86
Chemokines expressed by engineered bacteria recruit and orchestrate antitumor immunity DOI Creative Commons
Thomas Savage, Rosa L. Vincent,

Sarah S. Rae

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(10)

Published: March 8, 2023

Tumors use multiple mechanisms to actively exclude immune cells involved in antitumor immunity. Strategies overcome these exclusion signals remain limited due an inability target therapeutics specifically the tumor. Synthetic biology enables engineering of and microbes for tumor-localized delivery therapeutic candidates previously unavailable using conventional systemic administration techniques. Here, we engineer bacteria intratumorally release chemokines attract adaptive into tumor environment. Bacteria expressing activating mutant human chemokine CXCL16 (hCXCL16K42A) offer benefit mouse models, effect mediated via recruitment CD8+ T cells. Furthermore, presentation tumor-derived antigens by dendritic cells, a second engineered bacterial strain CCL20. This led type 1 cell synergized with hCXCL16K42A-induced provide additional benefit. In summary, recruit activate innate responses, offering new cancer immunotherapy strategy.

Language: Английский

Citations

84