Search Results (7)

Under physiological and pathological conditions, all cells release extracellular vesicles named exosomes, which act as transporters of lipidic, protein, and genetic material from parent to recipient cells. Neoplastic cells can secrete higher number of exosomes to exert pro-tumoral effects such as microenvironmental changes, disease progression, immunosuppression and drug-resistance. This holds true for both organ-specific cancers and hematologic malignancies. One of the most important components of exosomal cargo are microRNAs which can mediate all the abovementioned effects. More specifically, microRNAs are small non-coding RNAs, routinely detected through quantitative real-time PCR, which act as translational suppressors by regulating protein-coding genes. Considering their high stability in all body fluids and viability in circulation, research is currently focusing on this type of RNAs for the so called “liquid biopsy”, a non-invasive tool for disease diagnosis and longitudinal monitoring. However, several issues remain to be solved including the lack of standardized protocols for exosome isolation and miRNA detection. Starting with this premise, our review aims to provide a wide description of the known microRNA panels employed in the prominent hematological malignancies, which will hopefully redefine the approach to these very challenging diseases in the near future. Full article

Chimeric antigen receptor (CAR) cell therapy, encompassing CAR T, CAR NK, and CAR macrophage cells, demonstrates high efficacy in tumor treatment, conferring durable and effective responses, notably in hematologic malignancies. However, challenges persist in the manufacture of CAR cells, and treatment is associated with serious adverse events, notably cytokine release syndrome (CRS), a potentially life-threatening complication. Owing to the inherent properties of exosomes, CAR cell-derived exosomes offer distinct advantages in cancer therapeutics. CAR cells-derived exosomes retain the inherent tumor-killing function of the parent cells while also exhibiting key practical advantages, including wide availability, safety, and ease of storage and transport. Furthermore, CAR cell-derived exosomes can be combined with other tumor therapies; this combinatorial approach significantly enhances efficacy while reducing side effects. To accelerate the clinical translation of CAR cell-derived exosomes in tumor therapy, this paper reviews their biogenesis, engineering strategies, antitumor mechanisms and clinical evidence, including case studies of combination therapies with other antitumor modalities. Full article

Genetically engineered T and NK cells expressing a chimeric antigen receptor (CAR) are promising cytotoxic cells for the treatment of hematological malignancies and solid tumors. Despite the successful therapies using CAR-T cells, they have some disadvantages, such as cytokine release syndrome (CRS), neurotoxicity, or graft-versus-host-disease (GVHD). CAR-NK cells have lack or minimal cytokine release syndrome and neurotoxicity, but also multiple mechanisms of cytotoxic activity. NK cells are suitable for developing an “off the shelf” therapeutic product that causes little or no graft versus host disease (GvHD), but they are more sensitive to apoptosis and have low levels of gene expression compared to CAR-T cells. To avoid these adverse effects, further developments need to be considered to enhance the effectiveness of adoptive cellular immunotherapy. A promising approach to enhance the effectiveness of adoptive cellular immunotherapy is overcoming terminal differentiation or senescence and exhaustion of T cells. In this case, EVs derived from immune cells in combination therapy with drugs may be considered in the treatment of cancer patients, especially effector T and NK cells-derived exosomes with the cytotoxic activity of their original cells. Full article

Multiple myeloma (MM) is a hematological malignancy that is still incurable. The bone marrow microenvironment (BMM), with cellular and non-cellular components, can create a favorable environment for the survival, proliferation and migration of MM cells, which is the main reason for the failure of MM therapies. Many studies have demonstrated that exosomes play an important role in the tumor-supportive BMM. Exosomes are nanoscale vesicles that can be released by various cells. Some exosomes contribute to the pathogenesis and progression of MM. MM-derived exosomes act on different cells in the BMM, thereby creating an environment conducive to the survival and growth of MM cells. Owing to the important roles of exosomes in the BMM, targeting the secretion of exosomes may become an effective therapeutic strategy for MM. In addition, the abnormal expression of “cargos” in the exosomes of MM patients may be used to diagnose MM or used as part of a screen for the early prognoses of MM patients. Exosomes also have good biological properties, including safety, biocompatibility, stability and biodegradability. Therefore, the encapsulation of anti-cancer drugs in exosomes, along with surface modifications of exosomes with targeting molecules, are very promising strategies for cancer therapies—particularly for MM. In addition, DC-derived exosomes (DC-EXs) can express MHC-I, MHC-II and T cell costimulatory molecules. Therefore, DC-EXs may be used as a nanocarrier to deliver cancer vaccines in MM. This review summarizes the recent progress of exosome research regarding the pathogenesis of, diagnosis of, prognosis of and therapeutic strategies for MM. Full article

Cells can communicate through special “messages in the bottle”, which are recorded in the bloodstream inside vesicles, namely exosomes. The exosomes are nanovesicles of 30–100 nm in diameter that carry functionally active biological material, such as proteins, messanger RNA (mRNAs), and micro RNA (miRNAs). Therefore, they are able to transfer specific signals from a parental cell of origin to the surrounding cells in the microenvironment and to distant organs through the circulatory and lymphatic stream. More and more interest is rising for the pathological role of exosomes produced by cancer cells and for their potential use in tumor monitoring and patient follow up. In particular, the exosomes could be an appropriate index of proliferation and cancer cell communication for monitoring the minimal residual disease, which cannot be easily detectable by common diagnostic and monitoring techniques. The lack of unequivocal markers for tumor-derived exosomes calls for new strategies for exosomes profile characterization aimed at the adoption of exosomes as an official tumor biomarker for tumor progression monitoring. Full article

Small extracellular vesicles (small EVs) are commonly released by all cells, and are found in all body fluids. They are implicated in cell to cell short- and long-distance communication through the transfer of genetic material and proteins, as well as interactions between target cell membrane receptors and ligands anchored on small EV membrane. Beyond their canonical functions in healthy tissues, small EVs are strategically used by tumors to communicate with the cellular microenvironment and to establish a proper niche which would ultimately allow cancer cell proliferation, escape from the immune surveillance, and metastasis formation. In this review, we highlight the effects of hematological malignancy-derived small EVs on immune and stromal cells in the tumor microenvironment. Full article

Sarcomas are rare and heterogeneous cancers classically associated with a poor outcome. Sarcomas are 1% of the cancer but recent estimations indicate that sarcomas account for 2% of the estimated cancer-related deaths. Traditional treatment with surgery, radiotherapy, and chemotherapy has improved the outcome for some types of sarcomas. However, novel therapeutic strategies to treat sarcomas are necessary. TNF-related apoptosis-inducing ligand (TRAIL) is a death ligand initially described as capable of inducing apoptosis on tumor cell while sparing normal cells. Only few clinical trials have used TRAIL-based treatments in sarcoma, but they show only low or moderate efficacy of TRAIL. Consequently, novel TRAIL formulations with an improved TRAIL bioactivity are necessary. Our group has developed a novel TRAIL formulation based on tethering this death ligand on a lipid nanoparticle surface (LUV-TRAIL) resembling the physiological secretion of TRAIL as a trasmembrane protein inserted into the membrane of exosomes. We have already demonstrated that LUV-TRAIL shows an improved cytotoxic activity when compared to soluble recombinant TRAIL both in hematological malignancies and epithelial-derived cancers. In the present study, we have tested LUV-TRAIL in several human sarcoma tumor cell lines with different sensitivity to soluble recombinant TRAIL, finding that LUV-TRAIL was more efficient than soluble recombinant TRAIL. Moreover, combined treatment of LUV-TRAIL with distinct drugs proved to be especially effective, sensitizing even more resistant cell lines to TRAIL. Full article