Therapeutic advantage of combinatorial CAR T cell and chemo-therapies DOI Creative Commons

Meghan B Ward,

Amber B. Jones, Giedre Krenciute

и другие.

Pharmacological Reviews, Год журнала: 2024, Номер 77(1), С. 100011 - 100011

Опубликована: Окт. 7, 2024

Chimeric antigen receptor (CAR) T cell therapies have transformed outcomes for many patients with hematological malignancies. However, some do not respond to CAR treatment, and adapting cells solid brain tumors has been met challenges including a hostile tumor microenvironment poor persistence. Thus, it is unlikely that therapy alone will be sufficient consistent, complete clearance across cancer patients. Combinatorial of chemotherapeutics are promising approach overcoming this as could augment improved anti-tumor activity or work in tandem clear tumors. Herein, we review efforts towards achieving successful chemical drug combination therapies. We focus on approved these more easily translated the clinic, but also non-approved screens designed reveal new combinations. Together, highlights promise chemotherapy combinations specific how combinatorial overcomes faced by either monotherapy supports potential therapeutic strategy improve Significance Statement Improving currently available products via drastically expand types cancers number benefit from when neither achieve clearance. provide thorough current studying perspectives optimal ways identify effective moving forward.

Язык: Английский

Enhancing precision in cancer treatment: the role of gene therapy and immune modulation in oncology DOI Creative Commons

Emile M. Youssef,

Brandon Fletcher,

Dannelle Palmer

и другие.

Frontiers in Medicine, Год журнала: 2025, Номер 11

Опубликована: Янв. 13, 2025

Gene therapy has long been a cornerstone in the treatment of rare diseases and genetic disorders, offering targeted solutions to conditions once considered untreatable. As field advances, its transformative potential is now expanding into oncology, where personalized therapies address immune-related complexities cancer. This review highlights innovative therapeutic strategies, including gene replacement, silencing, oncolytic virotherapy, CAR-T cell therapy, CRISPR-Cas9 editing, with focus on their application both hematologic malignancies solid tumors. CRISPR-Cas9, revolutionary tool precision medicine, enables precise editing cancer-driving mutations, enhancing immune responses disrupting tumor growth mechanisms. Additionally, emerging approaches target ferroptosis—a regulated, iron-dependent form death—offering new possibilities for selectively inducing death resistant cancers. Despite significant breakthroughs, challenges such as heterogeneity, evasion, immunosuppressive microenvironment (TME) remain. To overcome these barriers, novel like dual-targeting, armored cells, combination checkpoint inhibitors ferroptosis inducers are being explored. rise allogeneic “off-the-shelf” offers scalable more accessible options. The regulatory landscape evolving accommodate advancements, frameworks RMAT (Regenerative Medicine Advanced Therapy) U.S. ATMP (Advanced Therapy Medicinal Products) Europe fast-tracking approval therapies. However, ethical considerations surrounding CRISPR-based editing—such off-target effects, germline ensuring equitable access—remain at forefront, requiring ongoing oversight. Advances non-viral delivery systems, lipid nanoparticles (LNPs) exosomes, improving safety efficacy By integrating innovations addressing concerns, poised revolutionize cancer treatment, providing durable, effective,

Язык: Английский

Процитировано

4
Reshaping the tumor immune microenvironment to improve CAR-T cell-based cancer immunotherapy DOI Creative Commons
X. Xia, Zongxin Yang,

Qisi Lu

и другие.

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Авг. 26, 2024

In many hematologic malignancies, the adoptive transfer of chimeric antigen receptor (CAR) T cells has demonstrated notable success; nevertheless, further improvements are necessary to optimize treatment efficacy. Current CAR-T therapies particularly discouraging for solid tumor treatment. The immunosuppressive microenvironment tumors affects cells, limiting treatment's effectiveness and safety. Therefore, enhancing cell infiltration capacity resolving responses within could boost anti-tumor effect. Specific strategies include structurally altering combined with targeted therapy, radiotherapy, or chemotherapy. Overall, monitoring status is beneficial in investigating viability such advancing therapy.

Язык: Английский

Процитировано

16
The next frontier in immunotherapy: potential and challenges of CAR-macrophages DOI Creative Commons
Jing Li,

Ping Chen,

Wenxue Ma

и другие.

Experimental Hematology and Oncology, Год журнала: 2024, Номер 13(1)

Опубликована: Авг. 5, 2024

Abstract Chimeric antigen receptor macrophage (CAR-MΦ) represents a significant advancement in immunotherapy, especially for treating solid tumors where traditional CAR-T therapies face limitations. CAR-MΦ offers promising approach to target and eradicate tumor cells by utilizing macrophages’ phagocytic antigen-presenting abilities. However, challenges such as the complex microenvironment (TME), variability expression, immune suppression limit their efficacy. This review addresses these issues, exploring mechanisms of action, optimal construct designs, interactions within TME. It also delves into ex vivo manufacturing CAR-MΦ, discussing autologous allogeneic sources importance stringent quality control. The potential synergies integrating with existing cancer like checkpoint inhibitors conventional chemotherapeutics are examined highlight possible enhanced treatment outcomes. Furthermore, regulatory pathways scrutinized alongside established protocols cells, identifying unique considerations essential clinical trials market approval. Proposed safety monitoring frameworks aim manage adverse events, cytokine release syndrome, crucial patient safety. Consolidating current research insights, this seeks refine therapeutic applications, overcome barriers, suggest future directions transition from experimental platforms standard care options.

Язык: Английский

Процитировано

13
Molecular dynamics at immune synapse lipid rafts influence the cytolytic behavior of CAR T cells DOI Creative Commons
Ahmed Z. Gad, Jessica S. Morris,

Lea Godret-Miertschin

и другие.

Science Advances, Год журнала: 2025, Номер 11(2)

Опубликована: Янв. 10, 2025

Chimeric antigen receptor T cells (CART) targeting CD19 through CD28.ζ signaling induce rapid lysis of leukemic blasts, contrasting with persistent tumor control exhibited by 4-1BB.ζ-CART. We reasoned that molecular dynamics at the CART immune synapse (CARIS) could explain differences in their rejection kinetics. observed CD28.ζ-CART engaged brief highly lethal CARIS and mastered serial killing, whereas 4-1BB.ζ-CART formed lengthy relied on robust expansion cooperative killing. analyzed membrane lipid rafts (mLRs) found that, upon engagement, CD28.ζ-CAR molecules rapidly but transiently translocated into mLRs, mobilizing microtubular organizing center lytic granules to CARIS. This enabled fast recovery sensitivity low target site density. In contrast, gradual accumulation 4-1BB.ζ-CAR LFA-1 mLRs built mechanically tonic mediating chronic Fas ligand–based The CD28.ζ- 4-1BB.ζ-CARIS distinct cytolytic behavior can guide engineering more adaptive effective cellular products.

Язык: Английский

Процитировано

1
CHIMERIC ANTIGEN RECEPTOR (CAR) T-CELL THERAPY: HARNESSING EXTRACELLULAR VESICLES FOR ENHANCED EFFICACY DOI Creative Commons

Beatrice Spokeviciute,

Sharad Kholia, Maria Felice Brizzi

и другие.

Pharmacological Research, Год журнала: 2024, Номер 208, С. 107352 - 107352

Опубликована: Авг. 13, 2024

A cutting-edge approach in cell-based immunotherapy for combating resistant cancer involves genetically engineered chimeric antigen receptor T (CAR-T) lymphocytes. In recent years, these therapies have demonstrated effectiveness, leading to their commercialization and clinical application against certain types of cancer. However, CAR-T therapy faces limitations, such as the immunosuppressive tumour microenvironment (TME) that can render cells ineffective, adverse side effects therapy, including cytokine release syndrome (CRS). Extracellular vesicles (EVs) are a diverse group membrane-bound particles released into extracellular environment by virtually all cell types. They essential intercellular communication, transferring cargoes proteins, lipids, various RNAs, DNA fragments target cells, traversing biological barriers both locally systemically. EVs play roles numerous physiological processes, with those from immune non-immune capable modulating system through activation or suppression. Leveraging this capability enhance could represent significant advancement overcoming its current limitations. This review examines landscape explores potential role augmenting therapeutic efficacy.

Язык: Английский

Процитировано

3
Evolving CAR T-Cell Therapy to Overcome the Barriers in Treating Pediatric Central Nervous System Tumors DOI
Andrea Timpanaro, Edward Song, Nour Emwas

и другие.

Cancer Discovery, Год журнала: 2025, Номер 15(5), С. 890 - 902

Опубликована: Апрель 29, 2025

CNS tumors are the leading cause of cancer-related death in children, highlighting dire need for new treatment strategies. CAR T cells represent a unique approach, distinct from cytotoxic chemotherapies and small-molecule inhibitors that have dominated clinical trial space decades. Phase I T-cell trials shown feasibility possible efficacy against pediatric tumors; however, many challenges must be overcome if these therapeutics going to beneficial most affected children. Although rapid translational development early-phase quickly evolved our understanding, community now yearns critical assessments open dialogue about overcoming remaining obstacles ahead.

Язык: Английский

Процитировано

0
Complex neural-immune interactions shape glioma immunotherapy DOI Creative Commons
Kun-Wei Song, Michael Lim, Michelle Monje

и другие.

Immunity, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Rich neural-immune interactions in the central nervous system (CNS) shape its function and create a unique immunological microenvironment for immunotherapy CNS malignancies. Far from now-debunked concept of "immune privilege," it is now understood that niches constant immune surveillance brain contribute multifaceted ways to health robustly influence approaches cancers. Challenges include immune-suppressive neurotoxicity-promoting crosstalk between brain, immune, tumor cells. Developing effective immunotherapies cancers will require deeper understanding these neural-immune-malignant cell interactions. Here, we review progress challenges gliomas spinal cord light highlight future work needed optimize promising gliomas.

Язык: Английский

Процитировано

0
CAR-T cells for H3K27-altered diffuse midline gliomas: where do we stand? DOI
Erica A. Power, Elena Millesi, Julian S. Rechberger

и другие.

Immunotherapy, Год журнала: 2024, Номер 16(12), С. 775 - 778

Опубликована: Июль 3, 2024

Язык: Английский

Процитировано

0
Therapeutic advantage of combinatorial CAR T cell and chemo-therapies DOI Creative Commons

Meghan B Ward,

Amber B. Jones, Giedre Krenciute

и другие.

Pharmacological Reviews, Год журнала: 2024, Номер 77(1), С. 100011 - 100011

Опубликована: Окт. 7, 2024

Chimeric antigen receptor (CAR) T cell therapies have transformed outcomes for many patients with hematological malignancies. However, some do not respond to CAR treatment, and adapting cells solid brain tumors has been met challenges including a hostile tumor microenvironment poor persistence. Thus, it is unlikely that therapy alone will be sufficient consistent, complete clearance across cancer patients. Combinatorial of chemotherapeutics are promising approach overcoming this as could augment improved anti-tumor activity or work in tandem clear tumors. Herein, we review efforts towards achieving successful chemical drug combination therapies. We focus on approved these more easily translated the clinic, but also non-approved screens designed reveal new combinations. Together, highlights promise chemotherapy combinations specific how combinatorial overcomes faced by either monotherapy supports potential therapeutic strategy improve Significance Statement Improving currently available products via drastically expand types cancers number benefit from when neither achieve clearance. provide thorough current studying perspectives optimal ways identify effective moving forward.

Язык: Английский

Процитировано

0