Reinforcing cancer immunotherapy with engineered porous hollow mycobacterium tuberculosis loaded with tumor neoantigens

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(2), P. e010150 - e010150

Published: Feb. 1, 2025

Background Enhancing antigen cross-presentation is essential for the development of a tumor neoantigen vaccine. One approach to stimulate antigen-presenting cells (APCs) uptake neoantigens. Mycobacterium tuberculosis (MTb) contains pathogen-associated molecular patterns (PAMPs) recognized by APCs and adhesion molecules that facilitate MTb invasion APCs. Therefore, we suggest using as carrier enhance APC phagocytosis neoantigens, thereby promoting cross-presentation. Methods The successful preparation (phMTb) was confirmed through electron confocal microscopy. Fluorescence microscopy used detect PAMPs on phMTb well observe its role in aiding dendritic (DCs) into endosomes or lysosomes. Flow cytometry assess retention phMTb, investigate DCs, evaluate their activation maturation status, examine presentation analyze immune draining lymph nodes tissues. efficacy vaccine formulations combination with anti-programmed cell death protein 1 (PD-1) antibody therapy assessed MC38 mouse models. Adverse effects were evaluated H&E staining major organs, assessment reproductive capability detection biochemical indices. Results engineered porous hollow successfully encapsulated model without adjuvant CpG. retained surface, similar parental MTb, enhancing DC containing neoantigens Vaccines formulated facilitated maturation, activation, promoted migration phMTb-laden DCs nodes, effector memory CD8 + T lymphocyte function. In murine models, immunization phMTb-formulated vaccines elicited robust tumor-specific cytotoxic response minimal adverse effects. Additionally, vaccination effectively reversed tumor’s immune-suppressive microenvironment. Concurrent administration PD-1 exhibited significant synergistic therapeutic Conclusions results our study highlight potential clinical translation personalized carrier.

Language: Английский

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Exploring the immuno-nano nexus: A paradigm shift in tumor vaccines

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 184, P. 117897 - 117897

Published: Feb. 7, 2025

Language: Английский

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SNARE proteins: Core engines of membrane fusion in cancer

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: unknown, P. 189148 - 189148

Published: July 1, 2024

Language: Английский

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Vax-Innate: improving therapeutic cancer vaccines by modulating T cells and the tumour microenvironment

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 21, 2024

Language: Английский

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Recent developments in myeloid immune modulation in cancer therapy

Trends in cancer, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Tissue-specific properties of type 1 dendritic cells in lung cancer: implications for immunotherapy

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(3), P. e010547 - e010547

Published: March 1, 2025

Checkpoint inhibitors have led to remarkable benefits in non-small cell lung cancer (NSCLC), yet response rates remain below expectations. High-dimensional analysis and mechanistic experiments clinical samples relevant NSCLC models uncovered the immune composition of tissues, providing invaluable insights into functional properties tumor-infiltrating T cells myeloid cells. Among cells, type 1 conventional dendritic (cDC1s) stand out for their unique ability induce effector CD8 against neoantigens coordinate antitumoral immunity. Notably, resident cDC1 are particularly abundant long-lived express a tissue-specific gene program, underscoring central role Here, we discuss recent on induction regulation responses cancer, separating it from tissue-agnostic knowledge generated heterogeneous tumor models. We focus most studies dissecting states spatial distribution across stages impact neoantigens. Finally, highlight gaps emerging strategies harness immunostimulatory potential.

Language: Английский

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Dendritic cells instruct T cell anti-tumor immunity and immunotherapy response

The Innovation Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 100128 - 100128

Published: Jan. 1, 2025

<p>Dendritic cells (DCs) are a heterogeneous population of antigen-presenting (APCs). They play pivotal roles in orchestrating innate and adaptive immune responses, particularly cancer. In tumor-draining lymph nodes (tdLNs), <i>de novo</i> priming occurs, where DCs present antigens to naive T cells, activating them initiating their clonal expansion. the tumor microenvironment (TME), intratumoral provide survival or co-stimulatory signals shape cell differentiation. However, scarcity dysfunctional states can greatly limit anti-tumor even be hijacked by tumor-related factors promote progression. Therefore, comprehensively understanding anti- pro-tumor activities is crucial. this review, we discuss ontogeny DC lineages emerging complexity states. Importantly, emphasize significant sustaining productive immunity. light these findings, also explore promising approaches for targeting boost immunity overcome resistance cancer immunotherapies. We propose that insights into rational design DC-based immunotherapeutic strategies against hold immense, underexploited potential.</p>

Language: Английский

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Microwave Ablation Combined with Flt3L Provokes Tumor‐Specific Memory CD8⁺ T Cells‐Mediated Antitumor Immunity in Response to PD‐1 Blockade

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 4, 2024

Abstract For medically inoperable non‐small cell lung cancer, microwave ablation (MWA) represents a super minimally invasive alternative treatment. However, tumor recurrence remains concern. Here, it is demonstrated that the combination of MWA with Flt3L significantly inhibits by CD8 + central memory T (T CM )‐like cell‐dependent antitumor immune responses within tumor‐draining lymph nodes (TdLN). TdLN‐T ‐like cells encompassed both tumor‐specific TSM ) and progenitor‐exhausted PEX cells. The expansion these markedly altered differentiation exhausted microenvironment (TME). predominantly differentiated into transitory effector‐like EX ‐int). elicited combined therapy was reliant on conventional dendritic (cDCs) likely specifically dependent migratory cDC1s (Mig cDC1s) TdLN. upregulation ICOSL pivotal in initiating cell‐mediated responses. Slc38a2 may be critical gene responsible for Mig following Finally, treatment enhanced efficacy immunotherapy based PD‐1 blockade. research thereby afforded novel strategic approach to forestall after therapy, while also providing foundational proof‐of‐concept impending clinical investigations.

Language: Английский

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Applications of Intravital Imaging in Cancer Immunotherapy

Bioengineering, Journal Year: 2024, Volume and Issue: 11(3), P. 264 - 264

Published: March 8, 2024

Currently, immunotherapy is one of the most effective treatment strategies for cancer. However, efficacy any specific anti-tumor can vary based on dynamic characteristics immune cells, such as their rate migration and cell-to-cell interactions. Therefore, understanding dynamics among cells involved in response inform optimization improvement existing strategies. In vivo imaging technologies use optical microscopy techniques to visualize movement behavior vivo, including response, thereby showing great potential application field cancer immunotherapy. this review, we briefly introduce technical aspects required imaging, fluorescent protein labeling, construction transgenic mice, various window chamber models. Then, discuss elucidation new phenomena mechanisms relating tumor that has been made possible by technology. Specifically, supported characterization T during checkpoint inhibitor therapy kinetic analysis dendritic cell vaccine therapy. Finally, provide a perspective challenges future research directions technology

Language: Английский

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Advancing Cancer Therapy: The Role of KIF20A as a Target for Inhibitor Development and Immunotherapy

Cancers, Journal Year: 2024, Volume and Issue: 16(17), P. 2958 - 2958

Published: Aug. 24, 2024

The analysis begins with a detailed examination of the gene expression and protein structure KIF20A, highlighting its interaction critical cellular components that influence key processes such as Golgi membrane transport mitotic spindle assembly. primary focus is on development specific KIF20A inhibitors, detailing their roles challenges encountered in enhancing efficacy, achieving specificity, overcoming tumor resistance, optimizing delivery systems. Additionally, it delves into prognostic value across multiple cancer types, emphasizing role novel tumor-associated antigen, which lays groundwork for targeted peptide vaccines. therapeutic efficacy these vaccines demonstrated recent clinical trials discussed. Future directions are proposed, including integration precision medicine strategies to personalize treatments use combination therapies improve outcomes. By concentrating significant potential both direct target inhibitors an antigen vaccines, this review sets foundation future research aimed at harnessing effective treatment.

Language: Английский

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