scholarly journals Disrupting tumour vasculature and recruitment of aPDL1-loaded platelets control tumour metastasis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hongjun Li ◽  
Zejun Wang ◽  
Zhaowei Chen ◽  
Tianyuan Ci ◽  
Guojun Chen ◽  
...  
Keyword(s):  
Cell Death ◽  
Immune Responses ◽  
Lung Metastases ◽  
Tumour Metastasis ◽  
Metastatic Lesions ◽  
Activated Platelets ◽  
Tumour Vasculature ◽  
Antitumour Effects ◽  
Tumour Blood

AbstractAlthough therapies of cancer are advancing, it remains challenging for therapeutics to reach the sites of metastasis, which accounts for majority of cancer associated death. In this study, we have developed a strategy that guides an anti-programmed cell death-ligand 1 (aPDL1) antibody to accumulate in metastatic lesions to promote anti-tumour immune responses. Briefly, we have developed a combination in which Vadimezan disrupts tumour blood vessels of tumour metastases and facilitates the recruitment and activation of adoptively transferred aPDL1-conjugated platelets. In situ activated platelets generate aPDL1-decorated platelet-derived microparticles (PMP) that diffuse within the tumour and elicit immune responses. The proposed combination increases 10-fold aPDL1 antibody accumulation in lung metastases as compared to the intravenous administration of the antibody and enhances the magnitude of immune responses leading to improved antitumour effects.

Tumor Microenvironment-Triggered In-Situ Cancer Vaccines with Dual Immunogenic Cell Death Inductions for Elevated Antitumor and Antimetastatic Therapy

Nanoscale ◽  
2021 ◽  
Author(s):  
Jun Lin ◽  
Binbin Ding ◽  
Pan Zheng ◽  
Dong Li ◽  
Meifang Wang ◽  
...  
Keyword(s):  
Cell Death ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Cancer Immunotherapy ◽  
Cancer Vaccines ◽  
High Specificity ◽  
The Body ◽  
Immunogenic Cell Death ◽  
Specific Antigens

Cancer vaccine is to make tumor-specific antigens into vaccines, which then are injected back into the body to activate immune responses for cancer immunotherapy. Despite the high specificity and therapeutic...

scholarly journals Localized cocktail chemoimmunotherapy after in situ gelation to trigger robust systemic antitumor immune responses

2020 ◽  
Vol 6 (10) ◽  
pp. eaaz4204 ◽  
Author(s):  
Yu Chao ◽  
Chao Liang ◽  
Huiquan Tao ◽  
Yaran Du ◽  
Di Wu ◽  
...  
Keyword(s):  
Cell Death ◽  
Immune Responses ◽  
Cancer Recurrence ◽  
Immune Checkpoint Blockade ◽  
Systemic Toxicity ◽  
Immunogenic Cell Death ◽  
In Situ Gelation ◽  
Immune Adjuvants ◽  
Immune Adjuvant

Currently, there is a huge demand to develop chemoimmunotherapy with reduced systemic toxicity and potent efficacy to combat late-stage cancers with spreading metastases. Here, we report several “cocktail” therapeutic formulations by mixing immunogenic cell death (ICD)–inducing chemotherapeutics and immune adjuvants together with alginate (ALG) for localized chemoimmunotherapy. Immune checkpoint blockade (ICB) antibody may be either included into this cocktail for local injection or used via conventional intravenous injection. After injection of such cocktail into a solid tumor, in-situ gelation of ALG would lead to local retention and sustained release of therapeutics to reduce systemic toxicity. The chemotherapy-induced ICD with the help of immune adjuvant would trigger tumor-specific immune responses, which are further amplified by ICB to elicit potent systemic antitumor immune responses in destructing local tumors, eliminating metastases and inhibiting cancer recurrence. Our strategy of combining clinically used agents for tumor-localized cocktail chemoimmunotherapy possesses great potential for clinical translation.

scholarly journals NIR responsive tumor vaccine in situ for photothermal ablation and chemotherapy to trigger robust antitumor immune responses

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lirong Zhang ◽  
Jingjing Zhang ◽  
Lixia Xu ◽  
Zijian Zhuang ◽  
Jingjin Liu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Tumor Vaccine ◽  
Oxidative Polymerization ◽  
Delivery Mode ◽  
Tumor Treatment ◽  
One Pot ◽  
Photothermal Ablation ◽  
Prolonged Retention ◽  
The One

Abstract Background Therapeutic tumor vaccine (TTV) that induces tumor-specific immunity has enormous potentials in tumor treatment, but high heterogeneity and poor immunogenicity of tumor seriously impair its clinical efficacy. Herein, a novel NIR responsive tumor vaccine in situ (HA-PDA@IQ/DOX HG) was prepared by integrating hyaluronic acid functionalized polydopamine nanoparticles (HA-PDA NPs) with immune adjuvants (Imiquimod, IQ) and doxorubicin (DOX) into thermal-sensitive hydrogel. Results HA-PDA@IQ NPs with high photothermal conversion efficiency (41.2%) and T1-relaxation efficiency were using HA as stabilizer by the one-pot oxidative polymerization. Then, HA-PDA@IQ loaded DOX via π-π stacking and mixed with thermal-sensitive hydrogel to form the HA-PDA@IQ/DOX HG. The hydrogel-confined delivery mode endowed HA-PDA@IQ/DOX NPs with multiple photothermal ablation performance once injection upon NIR irradiation due to the prolonged retention in tumor site. More importantly, this mode enabled HA-PDA@IQ/DOX NPs to promote the DC maturation, memory T cells in lymphatic node as well as cytotoxic T lymphocytes in spleen. Conclusion Taken together, the HA-PDA@IQ/DOX HG could be served as a theranostic tumor vaccine for complete photothermal ablation to trigger robust antitumor immune responses.

scholarly journals Biomarkers of Radiotherapy-Induced Immunogenic Cell Death

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 930
Author(s):  
Rianne D. W. Vaes ◽  
Lizza E. L. Hendriks ◽  
Marc Vooijs ◽  
Dirk De Ruysscher
Keyword(s):  
Cell Death ◽  
Immune Responses ◽  
Tumor Cells ◽  
Immunogenic Cell Death ◽  
Type I ◽  
Future Studies ◽  
Regulated Cell Death ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Potential Biomarkers

Radiation therapy (RT) can induce an immunogenic variant of regulated cell death that can initiate clinically relevant tumor-targeting immune responses. Immunogenic cell death (ICD) is accompanied by the exposure and release of damage-associated molecular patterns (DAMPs), chemokine release, and stimulation of type I interferon (IFN-I) responses. In recent years, intensive research has unraveled major mechanistic aspects of RT-induced ICD and has resulted in the identification of immunogenic factors that are released by irradiated tumor cells. However, so far, only a limited number of studies have searched for potential biomarkers that can be used to predict if irradiated tumor cells undergo ICD that can elicit an effective immunogenic anti-tumor response. In this article, we summarize the available literature on potential biomarkers of RT-induced ICD that have been evaluated in cancer patients. Additionally, we discuss the clinical relevance of these findings and important aspects that should be considered in future studies.

Combining PD-L1 Inhibitors with Immunogenic Cell Death Triggered by Chemo-Photothermal therapy via a Thermosensitive Liposome System to Stimulate Tumor-specific Immunological Response

Nanoscale ◽  
2021 ◽  
Author(s):  
Jie Yu ◽  
Xidong He ◽  
Zigui Wang ◽  
Yu Peng Wang ◽  
Sha Liu ◽  
...  
Keyword(s):  
Cell Death ◽  
Immune Responses ◽  
Photothermal Therapy ◽  
Immunological Response ◽  
Immune Checkpoint Blockade ◽  
Immunogenic Cell Death ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Thermosensitive Liposome ◽  
Liposome System

Immune checkpoint blockade (ICB) therapy in combination with immunogenic death (ICD) triggered by photothermal therapy (PTT) and oxaliplatin (OXA) treatment was expected to elicit both innate and adaptive immune responses...

The effect of polysaccharide-based hydrogels on the response of antigen presenting cell lines to immunomodulators

2021 ◽  
Author(s):  
Jin Teng, Melody Chung ◽  
Chi Ming Laurence Lau ◽  
Ying Chau
Keyword(s):  
Immune Responses ◽  
Cell Lines ◽  
Foreign Material ◽  
Antigen Presenting Cell ◽  
Antigen Presenting

Hydrogel presents as foreign material to the host and participates in immune responses which would skew the biofunctions of immunologic loads (antigen and adjuvants) for in-situ DC priming. This study...

scholarly journals An amphiphilic dendrimer as a light-activable immunological adjuvant for in situ cancer vaccination

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yongchao Wang ◽  
Ningqiang Gong ◽  
Chi Ma ◽  
Yuxuan Zhang ◽  
Hong Tan ◽  
...  
Keyword(s):  
Near Infrared ◽  
Infrared Light ◽  
Immune Memory ◽  
Toll Like Receptor ◽  
Tumour Site ◽  
Adjuvant Effect ◽  
Cancer Vaccination ◽  
Tumour Metastasis

AbstractImmunological adjuvants are essential for successful cancer vaccination. However, traditional adjuvants have some limitations, such as lack of controllability and induction of systemic toxicity, which restrict their broad application. Here, we present a light-activable immunological adjuvant (LIA), which is composed of a hypoxia-responsive amphiphilic dendrimer nanoparticle loaded with chlorin e6. Under irradiation with near-infrared light, the LIA not only induces tumour cell lysis and tumour antigen release, but also promotes the structural transformation of 2-nitroimidazole containing dendrimer to 2-aminoimidazole containing dendrimer which can activate dendritic cells via the Toll-like receptor 7-mediated signaling pathway. The LIA efficiently inhibits both primary and abscopal tumour growth and induces strong antigen-specific immune memory effect to prevent tumour metastasis and recurrence in vivo. Furthermore, LIA localizes the immunological adjuvant effect at the tumour site. We demonstrate this light-activable immunological adjuvant offers a safe and potent platform for in situ cancer vaccination.

scholarly journals Inhibition of B-cell death does not restore T-cell-dependent immune responses in CD40-deficient mice

Immunology ◽  
2003 ◽  
Vol 109 (4) ◽  
pp. 504-509
Author(s):  
Jesus Merino ◽  
Miguel A. Diez ◽  
Maria Muniz ◽  
Luis Buelta ◽  
Gabriel Nunez ◽  
...  
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Deficient Mice
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