Exploiting innate immunity for cancer immunotherapy

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Nov. 27, 2023

Abstract Immunotherapies have revolutionized the treatment paradigms of various types cancers. However, most these immunomodulatory strategies focus on harnessing adaptive immunity, mainly by inhibiting immunosuppressive signaling with immune checkpoint blockade, or enhancing immunostimulatory bispecific T cell engager and chimeric antigen receptor (CAR)-T cell. Although agents already achieved great success, only a tiny percentage patients could benefit from immunotherapies. Actually, immunotherapy efficacy is determined multiple components in tumor microenvironment beyond immunity. Cells innate arm system, such as macrophages, dendritic cells, myeloid-derived suppressor neutrophils, natural killer unconventional also participate cancer evasion surveillance. Considering that cornerstone antitumor response, utilizing immunity provides potential therapeutic options for control. Up to now, exploiting agonists stimulator interferon genes, CAR-macrophage -natural therapies, metabolic regulators, novel exhibited potent activities preclinical clinical studies. Here, we summarize latest insights into roles cells discuss advances arm-targeted strategies.

Language: Английский

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Exploring the dynamic interplay between cancer stem cells and the tumor microenvironment: implications for novel therapeutic strategies

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

Published: Oct. 2, 2023

Cancer stem cells (CSCs) have emerged as key contributors to tumor initiation, growth, and metastasis. In addition, CSCs play a significant role in inducing immune evasion, thereby compromising the effectiveness of cancer treatments. The reciprocal communication between microenvironment (TME) is observed, with TME providing supportive niche for CSC survival self-renewal, while CSCs, turn, influence polarization persistence TME, promoting an immunosuppressive state. Consequently, these interactions hinder efficacy current therapies, necessitating exploration novel therapeutic approaches modulate target CSCs. this review, we highlight intricate strategies employed by evade surveillance develop resistance therapies. Furthermore, examine dynamic interplay shedding light on how interaction impacts progression. Moreover, provide overview advanced that specifically which hold promise future clinical translational studies treatment.

Language: Английский

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Immune evasion in cell-based immunotherapy: unraveling challenges and novel strategies

Journal of Biomedical Science, Journal Year: 2024, Volume and Issue: 31(1)

Published: Jan. 12, 2024

Abstract Cell-based immunotherapies (CBIs), notably exemplified by chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy, have emerged as groundbreaking approaches for cancer therapy. Nevertheless, akin to various other therapeutic modalities, tumor cells employ counterstrategies manifest immune evasion, thereby circumventing the impact of CBIs. This phenomenon is facilitated an intricately immunosuppression entrenched within microenvironment (TME). Principal mechanisms underpinning evasion from CBIs encompass loss antigens, downregulation presentation, activation checkpoint pathways, initiation anti-apoptotic cascades, and induction dysfunction exhaustion. In this review, we delve into intrinsic underlying capacity resist proffer prospective stratagems navigate around these challenges.

Language: Английский

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Allogeneic CAR-T Therapy Technologies: Has the Promise Been Met?

Cells, Journal Year: 2024, Volume and Issue: 13(2), P. 146 - 146

Published: Jan. 12, 2024

This last decade, chimeric antigen receptor (CAR) T-cell therapy has become a real treatment option for patients with B-cell malignancies, while multiple efforts are being made to extend this other malignancies and broader patient populations. However, several limitations remain, including those associated the time-consuming highly personalized manufacturing of autologous CAR-Ts. Technologies establish "off-the-shelf" allogeneic CAR-Ts low alloreactivity currently developed, strong focus on gene-editing technologies. Although these technologies have many advantages, they also limitations, double-strand breaks in DNA safety risks as well lack modulation. As an alternative, non-gene-editing provide interesting approach support development future, possibilities fine-tuning gene expression easy development. Here, we will review different ways can be manufactured discuss which used. The biggest hurdles successful summarized, finally, overview current clinical evidence comparison its counterpart given.

Language: Английский

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Engineering allorejection-resistant CAR-NKT cells from hematopoietic stem cells for off-the-shelf cancer immunotherapy

Molecular Therapy, Journal Year: 2024, Volume and Issue: 32(6), P. 1849 - 1874

Published: April 6, 2024

The clinical potential of current FDA-approved chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy is encumbered by its autologous nature, which presents notable challenges related to manufacturing complexities, heightened costs, and limitations in patient selection. Therefore, there a growing demand for off-the-shelf universal therapies. In this study, we have generated CAR-engineered NKT (

Language: Английский

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Boosting CAR-T cell therapy through vaccine synergy

Trends in Pharmacological Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment landscape for hematological cancers. However, achieving comparable success in solid tumors remains challenging. Factors contributing to these limitations include scarcity of tumor-specific antigens (TSAs), insufficient CAR-T infiltration, and immunosuppressive tumor microenvironment (TME). Vaccine-based strategies are emerging as potential approaches address challenges, enhancing expansion, persistence, antitumor efficacy. In this review, we explore diverse vaccine modalities, including mRNA, peptide, viral vector, dendritic (DC)-based vaccines, their roles augmenting responses. Special focus is given recent clinical advancements combining mRNA-based vaccines with genitourinary addition, discuss crucial considerations optimizing dosing, scheduling, delivery maximize synergy, aiming refine combination strategy improve efficacy safety.

Language: Английский

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Advancing cell-based cancer immunotherapy through stem cell engineering

Cell stem cell, Journal Year: 2023, Volume and Issue: 30(5), P. 592 - 610

Published: March 21, 2023

Advances in cell-based therapy, particularly CAR-T cell have transformed the treatment of hematological malignancies. Although an important step forward for field, autologous therapies are hindered by high costs, manufacturing challenges, and limited efficacy against solid tumors. With ongoing progress gene editing culture techniques, engineered stem cells their application therapy poised to address some these challenges. Here, we review immunotherapy approaches, sources, engineering strategies, therapeutic platforms, clinical trials, as well challenges future directions field.

Language: Английский

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The future of affordable cancer immunotherapy

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Sept. 6, 2023

The treatment of cancer was revolutionized within the last two decades by utilizing mechanism immune system against malignant tissue in so-called immunotherapy. Two main developments boosted immunotherapy: 1) use checkpoint inhibitors, which are characterized a relatively high response rate mainly solid tumors; however, at cost serious side effects, and 2) chimeric antigen receptor (CAR)-T cells, were shown to be very efficient hematologic malignancies, but failed show clinical effectiveness tumors until now. In addition, active immunization individual is emerging, first products have reached approval. These new options cost-intensive not financially compensated health insurance many countries. Hence, strategies must developed make immunotherapy affordable improve cost-benefit ratio. this review, we discuss following strategies: leverage antigenicity “cold tumors” with reagents, microbiome-based as markers or therapeutics, 3) apply measures that adoptive cell therapy (ACT) cheaper, e.g., off-the-shelf products, 4) immunotherapies offer cheaper platforms, such RNA- peptide-based vaccines shared common antigens instead highly personal antigens, 5) small set predictive biomarkers “sequence everything” approach, 6) explore immunohistochemistry may direct therapies.

Language: Английский

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New cell sources for CAR-based immunotherapy

Biomarker Research, Journal Year: 2023, Volume and Issue: 11(1)

Published: May 6, 2023

Chimeric antigen receptor (CAR) T cell therapy, in which a patient's own lymphocytes are engineered to recognize and kill cancer cells, has achieved striking success some hematological malignancies preclinical clinical trials, resulting six FDA-approved CAR-T products currently available the market. Despite impressive outcomes, concerns about treatment failure associated with low efficacy or high cytotoxicity of cells remain. While main focus been on improving exploring alternative cellular sources for CAR generation garnered growing interest. In current review, we comprehensively evaluated other rather than conventional generation.

Language: Английский

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Biological functions and therapeutic applications of human mucosal-associated invariant T cells

Journal of Biomedical Science, Journal Year: 2025, Volume and Issue: 32(1)

Published: March 1, 2025

Abstract Mucosal-associated invariant T (MAIT) cells are a unique subset of innate-like lymphocytes that bridge innate and adaptive immunity. Characterized by their semi-invariant cell receptor (TCR) abundant localization in mucosal tissues, MAIT recognize microbial metabolites, primarily derived from the riboflavin biosynthesis pathway, presented major histocompatibility complex (MHC)-related protein 1 (MR1). This interaction, along with co-stimulatory signals, triggers rapid immune responses, including cytokine secretion cytotoxic activity, highlighting importance maintaining homeostasis combating infections. review provides an in-depth overview biology, development, activation pathways, functional diversity, protective roles immunity, contributions to diseases like cancer inflammatory bowel disease (IBD), context-dependent dual functions health pathology. also highlights emerging therapeutic potential immunotherapy. Their TCR specificity, abundance, tissue-homing properties make them ideal candidates for engineering novel therapies, such as chimeric antigen (CAR)-MAIT cells, targeting infections, cancers, autoimmune diseases. Challenges escape, exhaustion, CAR design optimization must be addressed enhance clinical efficacy. In summary, integral function, presents exciting opportunities treatment wide range Further research is essential unlock full these versatile cells.

Language: Английский

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