CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Янв. 30, 2023

In the last decade, Chimeric Antigen Receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach to fight cancers. This consists of genetically engineered immune cells expressing surface receptor, called CAR, that specifically targets antigens expressed on tumor cells. hematological malignancies like leukemias, myeloma, and non-Hodgkin B-cell lymphomas, adoptive CAR-T shown efficacy in treating chemotherapy refractory patients. However, value this remains inconclusive context solid tumors is restrained by several obstacles including limited trafficking infiltration, presence an immunosuppressive microenvironment, well adverse events associated with such therapy. Recently, CAR-Natural Killer (CAR-NK) CAR-macrophages (CAR-M) were introduced complement/alternative for tumors. CAR-NK could be favorable substitute since they do not require HLA compatibility have toxicity. Additionally, might generated large scale from sources which would suggest them off-the-shelf product. CAR-M immunotherapy its capabilities phagocytosis, tumor-antigen presentation, broad currently being investigated. Here, we discuss emerging role CAR-T, CAR-NK, We also highlight advantages drawbacks compared Finally, prospective solutions potential combination therapies enhance CAR-cells immunotherapy.

Язык: Английский

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Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Сен. 19, 2022

Abstract Cancers are highly complex diseases that characterized by not only the overgrowth of malignant cells but also an altered immune response. The inhibition and reprogramming system play critical roles in tumor initiation progression. Immunotherapy aims to reactivate antitumor overcome escape mechanisms tumors. Represented checkpoint blockade adoptive cell transfer, immunotherapy has seen tremendous success clinic, with capability induce long-term regression some tumors refractory all other treatments. Among them, blocking therapy, represented PD-1/PD-L1 inhibitors (nivolumab) CTLA-4 (ipilimumab), shown encouraging therapeutic effects treatment various tumors, such as non-small lung cancer (NSCLC) melanoma. In addition, advent CAR-T, CAR-M novel methods, entered a new era. At present, evidence indicates combination multiple methods may be one way improve effect. However, overall clinical response rate still needs improvement, which warrants development designs well discovery biomarkers can guide prescription these agents. Learning from past failure both basic research is for rational design studies future. this article, we describe efforts manipulate against discuss different targets types exploited promote

Язык: Английский

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Metastatic colorectal cancer: mechanisms and emerging therapeutics

Trends in Pharmacological Sciences, Год журнала: 2023, Номер 44(4), С. 222 - 236

Опубликована: Фев. 23, 2023

Язык: Английский

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Recent advances and applications of CRISPR-Cas9 in cancer immunotherapy

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Фев. 16, 2023

Abstract The incidence and mortality of cancer are the major health issue worldwide. Apart from treatments developed to date, unsatisfactory therapeutic effects cancers have not been addressed by broadening toolbox. advent immunotherapy has ushered in a new era solid tumors, but remains limited requires breaking adverse effects. Meanwhile, development advanced technologies can be further boosted gene analysis manipulation at molecular level. cutting-edge genome editing technology, especially clustered regularly interspaced short palindromic repeats (CRISPR-Cas9), demonstrated its potential break limits cancers. In this review, mechanism CRISPR-Cas9-mediated powerful CRISPR toolbox introduced. Furthermore, we focus on reviewing impact CRISPR-induced double-strand breaks (DSBs) (knockout or knockin). Finally, discuss CRISPR-Cas9-based genome-wide screening for target identification, emphasis spatial genomics, present comprehensive application challenges basic research, translational medicine clinics CRISPR-Cas9.

Язык: Английский

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Current and future concepts for the generation and application of genetically engineered CAR-T and TCR-T cells

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Март 6, 2023

Adoptive cell therapy (ACT) has seen a steep rise of new therapeutic approaches in its immune-oncology pipeline over the last years. This is great part due to recent approvals chimeric antigen receptor (CAR)-T therapies and their remarkable efficacy certain soluble tumors. A big focus ACT lies on T cells how genetically modify them target kill tumor cells. Genetically modified that are currently utilized either equipped with an engineered CAR or (TCR) for this purpose. Both strategies have advantages limitations. While CAR-T already used clinic, these face challenges when it comes treatment solid New designs next-generation might be able overcome hurdles. Moreover, CARs restricted surface antigens. TCR-T targeting intracellular antigens provide necessary qualities In review, we will summarize major advancements technology. cover ongoing clinical trials, discuss current challenges, assessment future directions within field.

Язык: Английский

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Adoptive cell therapy for cancer treatment

Exploration, Год журнала: 2023, Номер 3(4)

Опубликована: Июль 2, 2023

Abstract Adoptive cell therapy (ACT) is a rapidly growing anti‐cancer strategy that has shown promise in treating various cancer types. The concept of ACT involves activating patients’ own immune cells ex vivo and then transferring them back to the patients recognize eliminate cells. Currently, commonly used includes tumor‐infiltrating lymphocytes (TILs), genetically engineered cells, dendritic (DCs) vaccines. With advancement culture genetic engineering techniques, been clinics treat malignant hematological diseases many new ACT‐based regimens are different stages clinical trials. Here, representative approaches introduced opportunities challenges for translation discussed.

Язык: Английский

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CRISPR/Cas9: A Powerful Strategy to Improve CAR-T Cell Persistence

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(15), С. 12317 - 12317

Опубликована: Авг. 1, 2023

As an emerging treatment strategy for malignant tumors, chimeric antigen receptor T (CAR-T) cell therapy has been widely used in clinical practice, and its efficacy markedly improved the past decade. However, effect of CAR-T is not so satisfying, especially solid tumors. Even hematologic malignancies, a proportion patients eventually relapse after receiving infusions, owing to poor expansion persistence cells. Recently, CRISPR/Cas9 technology provided effective approach promoting proliferation cells body. This utilized generate memory phenotype, reduce exhaustion, screen new targets improve anti-tumor potential. In this review, we aim describe major causes limiting discuss application function. Finally, investigate trials CRISPR/Cas9-engineered cancer.

Язык: Английский

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Nucleic Acid Therapeutics: Successes, Milestones, and Upcoming Innovation

Nucleic Acid Therapeutics, Год журнала: 2024, Номер 34(2), С. 52 - 72

Опубликована: Март 20, 2024

Nucleic acid-based therapies have become the third major drug class after small molecules and antibodies. The role of nucleic has been strengthened by recent regulatory approvals tremendous clinical success. In this review, we look at obstacles that hindered field, historical milestones achieved, what is yet to be resolved anticipated soon. This review provides a view key innovations are expanding acid capabilities, setting stage for future therapeutics.

Язык: Английский

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Advancements and challenges in developing in vivo CAR T cell therapies for cancer treatment

EBioMedicine, Год журнала: 2024, Номер 106, С. 105266 - 105266

Опубликована: Авг. 1, 2024

The Chimeric Antigen Receptor (CAR) T cell therapy has emerged as a ground-breaking immunotherapeutic approach in cancer treatment. To overcome the complexity and high manufacturing cost associated with current ex vivo CAR products, alternative strategies to produce cells directly body have been developed recent years. These involve direct infusion of genes via engineered nanocarriers or viral vectors generate situ. This review offers comprehensive overview advancements development cell-targeted generation Additionally, it identifies challenges method potential these issues.

Язык: Английский

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Leveraging CRISPR gene editing technology to optimize the efficacy, safety and accessibility of CAR T-cell therapy

Leukemia, Год журнала: 2024, Номер unknown

Опубликована: Окт. 25, 2024

Язык: Английский

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