Trends in Research on Exosomes in Cancer Progression and Anticancer Therapy

Sinha, Dona; Roy, Sraddhya; Saha, Priyanka; Chatterjee, Nabanita; Bishayee, Anupam

doi:10.3390/cancers13020326

Cited by 78 publications

(50 citation statements)

References 207 publications

(152 reference statements)

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“…Patient-derived EVs were employed as an innovative cancer immunotherapy in several clinical trials, but this strategy did not reach sufficient efficacy [ 33 , 34 , 35 ]. Other lines of research have focused on modifying the content and function of EVs in various ways, toward the end-goal of specialized therapeutic EVs [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Long-Term Antitumor CD8+ T Cell Immunity Induced by Endogenously Engineered Extracellular Vesicles

Ferrantelli

Manfredi

Chiozzini

et al. 2021

Cancers

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We developed an innovative method to induce antigen-specific CD8+ T cytotoxic lymphocyte (CTL) immunity based on in vivo engineering of extracellular vesicles (EVs). This approach employs a DNA vector expressing a mutated HIV-1 Nef protein (Nefmut) deprived of the anti-cellular effects typical of the wild-type isoform, meanwhile showing an unusual efficiency of incorporation into EVs. This function persists even when foreign antigens are fused to its C-terminus. In this way, Nefmut traffics large amounts of antigens fused to it into EVs spontaneously released by the recipient cells. We previously provided evidence that mice injected with a DNA vector expressing the Nefmut/HPV16-E7 fusion protein developed an E7-specific CTL immune response as detected 2 weeks after the second immunization. Here, we extended and optimized the anti-HPV16 CD8+ T cell immune response induced by the endogenously engineered EVs, and evaluated the therapeutic antitumor efficacy over time. We found that the co-injection of DNA vectors expressing Nefmut fused with E6 and E7 generated a stronger anti-HPV16 immune response compared to that observed in mice injected with the single vectors. When HPV16-E6 and -E7 co-expressing tumor cells were implanted before immunization, all mice survived at day 44, whereas no mice injected with either void or Nefmut-expressing vectors survived until day 32 after tumor implantation. A substantial part of immunized mice (7 out of 12) cleared the tumor. When the cured mice were re-challenged with a second tumor cell implantation, none of them developed tumors. Both E6- and E7-specific CD8+ T immunities were still detectable at the end of the observation time. We concluded that the immunity elicited by engineered EVs, besides counteracting and curing already developed tumors, was strong enough to guarantee the resistance to additional tumor attacks. These results can be of relevance for the therapy of both metastatic and relapsing tumors.

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Section: Discussionmentioning

confidence: 99%

Long-Term Antitumor CD8+ T Cell Immunity Induced by Endogenously Engineered Extracellular Vesicles

Ferrantelli

Manfredi

Chiozzini

et al. 2021

Cancers

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“…It is interesting to note that Rab20 interacts with TPI1 in cells; yet only TPI1 but not Rab20 is detected in EVs released by MIHA cells ( Figure S10 ). Rab proteins plays crucial role in vesicular trafficking in cells and exosome biogenesis and secretion (Sinha et al., 2021 ). Rab5, an extensively studied endocytic protein, is essential for cargo packaging into clathrin‐coated pits with the assistance of clathrin and adaptor complex AP2 (Mclauchlan et al., 1998 ).…”

Section: Discussionmentioning

confidence: 99%

TPI1‐reduced extracellular vesicles mediated by Rab20 downregulation promotes aerobic glycolysis to drive hepatocarcinogenesis

Liu

Tey

Mao

et al. 2021

J of Extracellular Vesicle

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Rab GTPases are major mediators that ensure the proper spatiotemporal regulation of intracellular trafficking. Functional impairment and altered expression of Rab proteins have been revealed in various human cancers. There is an emerging evidence about the role of Rab proteins in the biogenesis of extracellular vesicles (EVs). In hepatocellular carcinoma (HCC), using RNA sequencing comparing expression profiles of adjacent non‐tumorous tissues and HCC, Rab20 is identified to be the most frequently downregulated Rab member in HCC. Functionally, restoration of Rab20 in metastatic HCC cells results in the release of EVs with a diminished activity to promote cell growth, motility and metastasis. Conversely, EVs released from normal liver cells with Rab20 knockdown loses suppressive effect on HCC cell growth and motility. Proteomic profiling revealed the level of triosephosphate isomerase 1 (TPI1), a glycolytic enzyme, in EVs to be positively associated with Rab20 expression of the releasing cells. TPI1 targeted to be expressed in EVs released by Rab20 knockdown cells compromises the oncogenic activity of EVs. Besides, EVs released by TPI1 knockdown cells recapitulates the promoting effect of EVs derived from HCC cells with Rab20 underexpression. Aerobic glycolysis is beneficial to the survival and proliferation of tumour cells. Here, we observed that the enhanced cell growth and motility are driven by the enhanced aerobic glycolysis induced by EVs with reduced TPI1. The addition of glycolytic inhibitor blocks the promoting effect of EVs with reduced TPI1. Taken together, our study provides a mechanistic link among tumour cell‐derived EVs and glucose metabolism in HCC with Rab20 deregulation.

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“…In addition, normal exosomes occur in body fluids, such as saliva, plasma, urine, milk, bile, ascites, and express diagnostic and therapeutic properties ( 13 , 91 , 92 ). Tumor exosomes are not only associated with tumor growth and metastasis, but also helps in identifying the disease conditions, thereby acting as ‘diagnostic markers’ ( 35 , 93 , 94 ).…”

Section: Methods Of Exosome Uptake By Cellsmentioning

confidence: 99%

Stem Cell-Derived Exosomes Potential Therapeutic Roles in Cardiovascular Diseases

Jayaraman

Gnanasampanthapandian

Rajasingh

et al. 2021

Front. Cardiovasc. Med.

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Owing to myocardial abnormalities, cardiac ailments are considered to be the major cause of morbidity and mortality worldwide. According to a recent study, membranous vesicles that are produced naturally, termed as “exosomes”, have emerged as the potential candidate in the field of cardiac regenerative medicine. A wide spectrum of stem cells has also been investigated in the treatment of cardiovascular diseases (CVD). Exosomes obtained from the stem cells are found to be cardioprotective and offer great hope in the treatment of CVD. The basic nature of exosomes is to deal with the intracellular delivery of both proteins and nucleic acids. This activity of exosomes helps us to rely on them as the attractive pharmaceutical delivery agents. Most importantly, exosomes derived from microRNAs (miRNAs) hold great promise in assessing the risk of CVD, as they serve as notable biomarkers of the disease. Exosomes are small, less immunogenic, and lack toxicity. These nanovesicles harbor immense potential as a therapeutic entity and would provide fruitful benefits if consequential research were focused on their upbringing and development as a useful diagnostic and therapeutic tool in the field of medicine.

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Trends in Research on Exosomes in Cancer Progression and Anticancer Therapy

Cited by 78 publications

References 207 publications

Long-Term Antitumor CD8+ T Cell Immunity Induced by Endogenously Engineered Extracellular Vesicles

Long-Term Antitumor CD8+ T Cell Immunity Induced by Endogenously Engineered Extracellular Vesicles

TPI1‐reduced extracellular vesicles mediated by Rab20 downregulation promotes aerobic glycolysis to drive hepatocarcinogenesis

Stem Cell-Derived Exosomes Potential Therapeutic Roles in Cardiovascular Diseases

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