Enhancing Cancer Immunotherapeutic Efficacy with Sonotheranostic Strategies

Author(s):  
Ayesha Zafar ◽  
Murtaza Hasan ◽  
Tuba Tariq ◽  
Zhifei Dai
2021 ◽  
Vol 22 (15) ◽  
pp. 8037
Author(s):  
Akshita Chauhan ◽  
Tabassum Khan ◽  
Abdelwahab Omri

The aim of cancer immunotherapy is to reactivate autoimmune responses to combat cancer cells. To stimulate the immune system, immunomodulators, such as adjuvants, cytokines, vaccines, and checkpoint inhibitors, are extensively designed and studied. Immunomodulators have several drawbacks, such as drug instability, limited half-life, rapid drug clearance, and uncontrolled immune responses when used directly in cancer immunotherapy. Several strategies have been used to overcome these limitations. A simple and effective approach is the loading of immunomodulators onto gold-based nanoparticles (GNPs). As gold is highly biocompatible, GNPs can be administered intravenously, which aids in increasing cancer cell permeability and retention time. Various gold nanoplatforms, including nanospheres, nanoshells, nanorods, nanocages, and nanostars have been effectively used in cancer immunotherapy. Gold nanostars (GNS) are one of the most promising GNP platforms because of their unusual star-shaped geometry, which significantly increases light absorption and provides high photon-to-heat conversion efficiency due to the plasmonic effect. As a result, GNPs are a useful vehicle for delivering antigens and adjuvants that support the immune system in killing tumor cells by facilitating or activating cytotoxic T lymphocytes. This review represents recent progress in encapsulating immunomodulators into GNPs for utility in a cancer immunotherapeutic regimen.


2020 ◽  
Author(s):  
Dan Liu ◽  
Jiale Liu ◽  
Bing Ma ◽  
Bo Deng ◽  
Haiyan Xu ◽  
...  

Abstract Background: Biomimetic nanoparticles have potential applications in many fields for their favorable properties. Results: Here, we developed a self-adjuvanting biomimetic anti-tumor nanovaccine, which was self-assembled with an amphiphilic conjugate synthetized with phospholipids of 1, 2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and hydrophilic Toll-like receptor (TLR9) agonists CpG ODN. The nanovaccine could not only provide effective initial antigens stimulation and sustained long-term antigen supply with a controlled release, but also induce antigens cross-presentation via MHC-I pathway initiating CD8+ T-cell responses. Moreover, the dense nucleotides shell around the nanovaccine could promote antigens endocytosis via various receptor-mediated pathways into dendritic cells. And CpG ODN interacted with TLR9 triggering the cytokines secretion of TNF-α and IL-10 further boosted the anti-tumor humoral and cellular immune responses, which led to significant tumor suppressive effect and remarkable survival prolongation. Conclusions: So, this nanovaccine self-assembled with phospholipid-nucleotide amphiphiles can serve as a safe, simple and efficient approach for anti-tumor immunotherapy.


Biomedicines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 105 ◽  
Author(s):  
Marta Martinez-Lage ◽  
Pilar Puig-Serra ◽  
Pablo Menendez ◽  
Raul Torres-Ruiz ◽  
Sandra Rodriguez-Perales

Cancer is the second leading cause of death globally and remains a major economic and social burden. Although our understanding of cancer at the molecular level continues to improve, more effort is needed to develop new therapeutic tools and approaches exploiting these advances. Because of its high efficiency and accuracy, the CRISPR-Cas9 genome editing technique has recently emerged as a potentially powerful tool in the arsenal of cancer therapy. Among its many applications, CRISPR-Cas9 has shown an unprecedented clinical potential to discover novel targets for cancer therapy and to dissect chemical-genetic interactions, providing insight into how tumours respond to drug treatment. Moreover, CRISPR-Cas9 can be employed to rapidly engineer immune cells and oncolytic viruses for cancer immunotherapeutic applications. Perhaps more importantly, the ability of CRISPR-Cas9 to accurately edit genes, not only in cell culture models and model organisms but also in humans, allows its use in therapeutic explorations. In this review, we discuss important considerations for the use of CRISPR/Cas9 in therapeutic settings and major challenges that will need to be addressed prior to its clinical translation for a complex and polygenic disease such as cancer.


2021 ◽  
Vol 9 (1) ◽  
pp. 84-92
Author(s):  
Dan Liu ◽  
Jiale Liu ◽  
Bing Ma ◽  
Bo Deng ◽  
Xigang Leng ◽  
...  

The biomimetic nanovaccines not only promoted antigens endocytosis into dendritic cells via receptor-mediated pathways but also induced antigens cross-presentation eliciting CD8+ T-cell responses. CPG-ODN as an adjuvant further enhanced the anti-tumor immune responses.


2020 ◽  
Vol 69 (6) ◽  
pp. 1057-1069 ◽  
Author(s):  
Yu-Jie Zhou ◽  
Gui-Qi Zhu ◽  
Xiao-Fan Lu ◽  
Kenneth I. Zheng ◽  
Qi-Wen Wang ◽  
...  

2020 ◽  
Vol 21 (12) ◽  
pp. 4317 ◽  
Author(s):  
Nishant P. Patel ◽  
Peng Guan ◽  
Devika Bahal ◽  
Tanwir Hashem ◽  
Felix Scheuplein ◽  
...  

Invariant natural killer T cells (iNKTs) directly kill tumor cells and trans-activate the anti-tumor functions of dendritic cells (DC), natural killer (NK) cells, and T and B cells. As such, iNKTs serve as a powerful tool for use in cell-based cancer immunotherapy. iNKT cell activation commonly requires engagement of the invariant T cell receptor (iTCR) by CD1d presenting glycolipid antigens. However, transformed cells often down-regulate CD1d expression, which results in a reduction of iNKT cell anti-tumor functions. One approach to circumvent this critical barrier to iNKT cell activation is to develop an agonistic antibody that binds directly to the iTCR without the requirement for CD1d-mediated antigen presentation. To this end, we have characterized the iNKT cell stimulatory properties of NKTT320, a novel, recombinant, humanized, monoclonal antibody that binds selectively and with high affinity to human iTCRs. Strikingly, immobilized NKTT320 mediated robust iNKT cell activation (upregulation of CD25 and CD69) and proliferation (carboxyfluorescein succinimidyl ester (CFSE) dilution), as well as Th1 and Th2 cytokine production. Additionally, iNKTs stimulated by plate-bound NKTT320 exhibited increased intracellular levels of granzyme B and degranulation (exposure of CD107 on the cell surface). Furthermore, both soluble and immobilized NKTT320 induced iNKT cell-mediated activation of bystander immune cells, suggesting that this novel anti-iTCR antibody facilitates both direct and indirect iNKT cell cytotoxicity. These studies are significant, as they provide a framework by which iNKT cell anti-cancer functions could be enhanced for therapeutic purposes.


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