Nanobody-based CAR-T cells for cancer immunotherapy.

Chimeric antigen receptor T-cell (CAR-T) therapy is the result of combining genetic engineering-based cancer immunotherapy with adoptive cell therapy (ACT). CAR-T therapy has been successful in treating various types of hematological cancers. CARs are receptors made of an extracellular domain, a membrane-spanning domain, and an intracellular domain. The extracellular domain of CARs harbors an antigen-targeting domain responsible for recognizing and binding cell surface-expressed target antigens. Conventionally, the single-chain fragment variable (scFv) of a monoclonal antibody (mAb) is used as the antigen-targeting domain of CARs. However, of late, researchers have exploited nanobodies for this aim based on numerous rationales including the small size of nanobodies, their stability, specificity, and high affinity, and their easy and feasible development process. Many findings have confirmed that nanobody-based CAR-Ts can be as functional as scFv-based CAR-Ts in preclinical and clinical settings. In this review, we discuss the advantages and disadvantages of scFvs and nanobodies in regards to their application as the targeting domain of CARs. Ultimately, we discuss various CAR target antigens which have been targeted using nanobody-based CAR-T cells for the treatment of different types of malignancies.

Evaluation of trace elements pollution in deposited dust on residential areas and agricultural lands around Pb/Zn mineral areas using modified pollution indices.

Dust deposited on residential and agricultural lands can have serious consequences for the ecosystem when toxic trace elements are present. This study aimed to assess the ecological risk of the trace elements found in the deposited dust around the Mehdi Abad Pb/Zn mine, Yazd, Iran, using several modified pollution indices. The dust samples were collected by the grid method and a Marble Dust Collector (MDCO) sampler to evaluate the concentration of thirty trace elements: nickel (Ni), lead (Pb), barium (Ba), beryllium (Be), chromium (Cr), copper (Cu), dysprosium (Dy), lanthanum (La), lithium (Li), niobium (Nb), tin (Sn), neodymium (Nd), praseodymium (Pr), rubidium (Rb), Ferrum (Fe), sulfur (S), selenium (Se), strontium (Sr), tantalum (Ta), terbium (Tb), zirconium (Zr), tellurium (Te), thorium (Th), titanium (Ti), uranium (U), vanadium (V), yttrium (Y), ytterbium (Yb), thulium (Tm), and cobalt (Co). This study employed multivariate statistical techniques, including Hierarchical cluster analysis (HCA) and the IDW interpolation technique, as well as modified pollution indices such as Enrichment Factor (EF), Modified Pollution Index (MPI), Modified Potential Ecological Risk Index (MRI), and Modified Hazard Quotient (mHQ). All the statistical data analyses were performed via SPSS Statistics, version 22.00. The HCA results showed that all of these trace elements, except Fe, form a group and had similar behavior. The average levels of all elements in the dust samples except for Cr, S, Sr, Ta, Tb, and Te exceeded the background value. The results confirmed that both anthropogenic activities and natural factors were responsible for the trace elements found in the dust. The average EF value for Pb (43.26) indicated its extremely high enrichment in the study area. The MPI, mHQ, and MRI results showed that 33%, 100%, and 33.33% of the dust samples were in the heavily polluted, extreme severity, and high risk categories, respectively. The IDW analysis results revealed that the highest value of the MRI and mHQ indices was in agricultural lands and residential areas; the predominant wind direction also played a role in transferring the elements from the mine to these areas. In general, the results indicated that mining activities increased the ecological risk in Mehdi Abad due to the presence of trace elements, especially Pb.

Comparison of superantigens and attachment factors genes of Staphylococcus aureus in clinical isolates and nasal colonizers in the same patients.

BACKGROUND: Staphylococcus aureus (S. aureus) is a bacterial pathogen can cause a wide range of nosocomial infections. Nasal colonization by S.aureus plays important role both in the epidemiology and pathogenesis of infection. OBJECTIVES: The purpose of this study was to investigate the association of clinical isolates and nasal colonizers of S. aureus in the same patients by molecular methods, and their antibiotic susceptibility pattern. METHODS: A total of 181 S. aureus isolates were collected from 100 patients admitted that including 100 clinical isolates and 81 nasal swabs from the same patients (19 cases were found as noncarriers). Superantigens and adhesion genes were identified by PCR. Molecular typing of the isolates was performed by repetitive element polymerase chain reaction (Rep-PCR). Antimicrobial susceptibility pattern of the isolates was conducted by disk diffusion. MIC of the isolates to vancomycin was determined by microbroth dilution. The ability of S. aureus isolates to form biofilm was determined by microtiter plate assay. RESULTS: The most frequent adhesion gene in both clinical isolates and nasal colonizer was clfA with 93% and 76%, respectively. Staphylococcal enterotoxin A (SEA) was the most commonly superantigen (68%) in both nasal colonizers (71.6%) and clinical isolates (65%). The highest resistance rate was to erythromycin (45.3%) with 36% and 56.8% in clinical and nasal colonizer isolates, respectively. All S. aureus isolates were susceptible to linezolid and vancomycin. Multiple drug resistance (MDR) was detected in 36% (n = 65) of the isolates. Biofilm formation was identified in 160 (88.4%) isolates with 87% and 90% in clinical isolates and nasal colonizers, respectively. Repetitive element polymerase chain reaction (Rep-PCR) typing divided 181 S. aureus isolates into six clusters. Twelve isolates from clinical isolates and nasal carriers were closely related. CONCLUSION: There is a high concordance rate between colonizing and clinical isolates of S. aureus in terms of adhesion factors and superantigen genes. It is suggested that nasal decolonization could be effective in the preventing of S. aureus infections.

Role of MexAB-OprM and MexXY-OprM efflux pumps and class 1 integrons in resistance to antibiotics in burn and Intensive Care Unit isolates of Pseudomonas aeruginosa.

BACKGROUND: The overexpression of efflux pumps and existence of class 1 integrons are the most important mechanisms that contribute to antimicrobial resistance in Pseudomonas aeruginosa especially in burn and Intensive Care Units (ICUs). The present study evaluated the role of MexAB-OprM and MexXY-OprM efflux pumps and class 1 integrons in resistance to antibiotics in burn and ICU isolates of P. aeruginosa. METHODS: Fifteen burn and forty-two ICU isolates were obtained from four hospitals in Northwest Iran. The isolates were identified and evaluated by the disk diffusion and agar dilution methods for determining antibiotic resistances. The presence of class 1 integrons and associated resistance gene cassettes were detected by PCR and sequencing of the products. The expression levels of efflux pumps were evaluated by phenotypic and genotypic (Quantitative Real-time PCR) methods. The isolates were genotyped by Random Amplified Polymorphic DNA Typing (RAPD-PCR). RESULTS: All burn isolates were integron positive and Multi-drug resistant (MDR), while 78.5% and 69% of ICU isolates were found as MDR and integron positive, respectively. The aadB gene was the most prevalent gene cassette (63.6%) followed by aacA4 (47.7%). Thirty-nine (68.4%) and 43 (75.4%) isolates exhibited an overexpression of MexAB-OprM and MexXY-OprM. Among burn isolates, 80% and 86.6% of them were mexB and mexY overexpressed, while 64.2% and 71.4% of ICU isolates exhibited mexB and mexY overexpression, correspondingly. The isolates were genotyped as 24 different RAPD profiles and were grouped into 15 clusters. CONCLUSIONS: The data suggested that class 1 integron had a more significant role than efflux pumps in resistance to beta-lactams and aminoglycosides in burn and ICUs except for gentamicin in burn isolates. Based on our data, it is possible that efflux pumps were not the main cause of high-level resistance to antibiotics.