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Flexible Aptamer-based Nucleolin-targeting Cancer Treatment Modalities: A Focus on Immunotherapy, Radiotherapy, and Phototherapy

Pouya Safarzadeh Kozani, Pooria Safarzadeh Kozani, Fatemeh Rahbarizadeh
Journal Paper , Issue In Press, 2030 December 31, {Pages }

Abstract

: Cancer radiotherapy and phototherapy are well-recognized as alternative approaches for chemotherapy-resistant malignancies. Additionally, recently cancer immunotherapy is introduced as a potential therapeutic option for cancer treatment, which has had its ups and downs despite the reported heart-warming outcomes. Nevertheless, it is proved that nanotechnology-facilitated approaches might facilitate the success of these modalities. The nucleolin-targeting aptamer, AS1411, is one of the various aptamers utilized for reducing nanocarriers carrying radiosensitizers and photosensitizers. Recently, the potential applicability of this aptamer has been investigated in cancer immunotherapy. In this review, we, firstly, discussed how aptamer-mediat

Combined transcriptional, translational and cell surface targeted gene therapy of HER2-positive breast cancer stem cells in three-dimentional cell culture

Cobra Moradian, Fatemeh Rahbarizadeh
Journal Paper , 2021 February 5, {Pages }

Abstract

PurposeBreast Cancer Stem Cells (BCSCs) resist conventional treatments and cause tumor recurrence. Almost 25% of breast cancers overexpress human epidermal growth factor receptor-2 (HER2). Here we developed a novel multi-targeted nanosystem to speci cally eradicate HER2-positive BCSCs.

CRISPR/Cas9-mediated knockout of clinically relevant alloantigenes in human primary T cells

Elahe Kamali, Fatemeh Rahbarizadeh, Zohreh Hojati, Morten Fr?din
Journal PaperBMC biotechnology , Volume 21 , Issue 1, 2021 December , {Pages 10-Jan }

Abstract

The ability of CRISPR/Cas9 to mutate any desired genomic locus is being increasingly explored in the emerging area of cancer immunotherapy. In this respect, current efforts are mostly focused on the use of autologous (i.e. patient-derived) T cells. The autologous approach, however, has drawbacks in terms of manufacturing time, cost, feasibility and scalability that can affect therapeutic outcome or wider clinical application. The use of allogeneic T cells from healthy donors may overcome these limitations. For this strategy to work, the endogenous T cell receptor (TCR) needs to be knocked out in order to reduce off-tumor, graft-versus-host-disease (GvHD). Furthermore, CD52 may be knocked out in the donor T cells, since this leaves them resi

Strategies for Dodging the Obstacles in CAR T Cell Therapy

Pooria Safarzadeh Kozani, Pouya Safarzadeh Kozani, Fatemeh Rahbarizadeh, Shahryar Khoshtinat Nikkhoi
Journal Paper , Volume 11 , 2021 January , {Pages 924 }

Abstract

Chimeric antigen receptor (CAR) T cell therapy has offered cancer patients a new alternative therapeutic choice in recent years. This novel type of therapy holds tremendous promise for the treatment of various hematologic malignancies including B-cell acute lymphoblastic leukemia (B-ALL) and lymphoma. However, CAR T cell therapy has experienced its ups and downs in terms of toxicities and efficacy shortcomings. Adverse events such as cytokine release syndrome (CRS), neurotoxicity, graft rejection, on-target off-tumor toxicities, and tumor relapse have tied the rescuing hands of CAR T cell therapies. Moreover, in the case of solid tumor treatment, CAR T cell therapies have not yielded encouraging results mainly due to challenges such as the

A novel missense variant in the LMNB2 gene causes progressive myoclonus epilepsy

Fardin Soleimanipour, Ehsan Razmara, Fatemeh Rahbarizadeh, Elnaz Fallahi, Mehrnoosh Khodaeian, Ali Reza Tavasoli, Masoud Garshasbi
Journal PaperActa Neurologica Belgica , 2021 March 30, {Pages 09-Jan }

Abstract

Progressive myoclonus epilepsies (PMEs) are a group of disorders embracing myoclonus, seizures, and neurological dysfunctions. Because of the genetic and clinical heterogeneity, a large proportion of PMEs cases have remained molecularly undiagnosed. The present study aimed to determine the underlying genetic factors that contribute to the PME phenotype in an Iranian female patient. We describe a consanguineous Iranian family with autosomal recessive PME that had remained undiagnosed despite extensive genetic and pathological tests. After performing neuroimaging and clinical examinations, due to heterogeneity of PMEs, the proband was subjected to paired-end whole-exome sequencing and the candidate variant was confirmed by Sanger sequencing.

A VHH-Based anti-MUC1 chimeric antigen receptor for specific retargeting of human primary T cells to MUC1-positive cancer cells

Alireza Rajabzadeh, D Ahmadvand, MK Salmani, F Rahbarizadeh, Amir Ali Hamidieh
Journal PaperCell journal , Volume 22 , Issue 4, 2021 January , {Pages 502-513 }

Abstract

Objective: Immunotherapy with redirected T cells that express a chimeric antigen receptor (CAR) is a promising prospect in cancer treatment. Most CARs use murine-derived single-chain variable fragments (scFvs) as an antigen targeting moiety, which may lead to host immunogenic responses and engineered T cell disappearance. It seems that development of less immunogenic CARs, such as CARs composed of the camelid variable domain of heavy chain antibodies (VHHs) may likely overcome this obstacle. Here, we improved the expression of the VHH-based anti-MUC1 CAR gene construct using a third generation lentiviral vector in primary human T cells and assessed its effect on antigen specific targeting, activation and cytotoxicity of redirected human T c

Novel antigens of CAR T cell therapy: New roads; old destination

Pooria Safarzadeh Kozani, Pouya Safarzadeh Kozani, Fatemeh Rahbarizadeh
Journal Paper , Volume 14 , Issue 7, 2021 July 1, {Pages 101079 }

Abstract

Chimeric antigen receptor T cell (CAR-T) therapy has so far proved itself as a reliable therapeutic option for the treatment of relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL), diffuse large B-cell lymphoma (DLBCL), multiple myeloma (MM), and mantle cell lymphoma (MCL). However, this picture is not as colorful when it comes to the treatment of solid tumors mainly due to the lack of definitive tumor antigens, as well as the immunosuppressive tumor microenvironments and poor CAR-T infiltration. The recent developments in bioinformatics and cell biology, such as single-cell RNA sequencing, have offered silver linings in the subject of tumor antigen discovery. In the current review, we summarize the development of some CAR

Chemotherapeutic, Toxin, and Therapeutic Protein Delivery via Nucleolin Aptamer-functionalized Nanoplatforms for Targeted Cancer Therapy

Pouya Safarzadeh Kozani, Pooria Safarzadeh Kozani, Fatemeh Rahbarizadeh
Journal Paper , Volume 1 , Issue 1, 2021 February 28, {Pages }

Abstract

Context: Nucleolin is a protein abundantly present in the nucleolus, but its expression on the surface of cells is potentially associated with various types of malignancies. Evidence Acquisition: So far, several nucleolin-targeting strategies, including nucleolin-targeting peptides, anti-nucleolin pseudopeptides, anti-nucleolin antibodies, and the anti-nucleolin aptamers, AS1411, have been developed and investigated in different types of studies. Results: The AS1411 aptamer has been known as the outstanding approach for targeting nucleolin with superior specificity and therapeutic potential in comparison with other targeting strategies. Conclusions: In this review, we highlight different nucleolin-targeting strategies for the targeted deliv

Strategies for dodging the obstacles in CAR T cell therapy

Pooria Safarzadeh Kozani, Pouya Safarzadeh Kozani, Fatemeh Rahbarizadeh, Shahryar Khoshtinat Nikkhoi
Journal Paper , Volume 11 , 2021 January , {Pages }

Abstract

Chimeric antigen receptor (CAR) T cell therapy has offered cancer patients a new alternative therapeutic choice in recent years. This novel type of therapy holds tremendous promise for the treatment of various hematologic malignancies including B-cell acute lymphoblastic leukemia (B-ALL) and lymphoma. However, CAR T cell therapy has experienced its ups and downs in terms of toxicities and efficacy shortcomings. Adverse events such as cytokine release syndrome (CRS), neurotoxicity, graft rejection, on-target off-tumor toxicities, and tumor relapse have tied the rescuing hands of CAR T cell therapies. Moreover, in the case of solid tumor treatment, CAR T cell therapies have not yielded encouraging results mainly due to challenges such as the

Chemotherapeutic, Toxin, and Therapeutic Protein Delivery via Nucleolin Aptamer-functionalized Nanoplatforms for Targeted Cancer Therapy

Pouya Safarzadeh Kozani, Pooria Safarzadeh Kozani, Fatemeh Rahbarizadeh
Journal Paper , 2021 January , {Pages }

Abstract

Nucleolin is a protein abundantly present in the nucleolus, but its expression on the surface of cells is potentially associated with various types of malignancies. So far, several nucleolin-targeting strategies, including the nucleolin-targeting peptide, anti-nucleolin pseudopeptides, anti-nucleolin antibodies, and the anti-nucleolin aptamer, AS1411, have been developed and investigated in different types of studies. The AS1411 aptamer has been known as the outstanding approach for targeting nucleolin with superior specificity and therapeutic potential in comparison with other targeting strategies. In this review, we highlight different nucleolintargeting strategies for the targeted delivery of chemotherapeutic drugs, proteins with therape

CAR-T cell therapy in T-cell malignancies: Is success a low-hanging fruit?

P Safarzadeh Kozani, P Safarzadeh Kozani, F Rahbarizadeh
Journal Paper , , {Pages }

Abstract

Liposome-based nanocarriers loaded with anthrax lethal factor and armed with anti-CD19 VHH for effectively inhibiting MAPK pathway in B cells

SR Banihashemi, F Rahbarizadeh, AZ Hosseini, D Ahmadvand, ...
Journal Paper , , {Pages }

Abstract

Aptamer-Assisted Delivery of Nucleotides with Tumor-Suppressing Properties for Targeted Cancer Therapies

P Safarzadeh Kozani, P Safarzadeh Kozani, F Rahbarizadeh
Journal Paper , , {Pages }

Abstract

Anti-HER2 VHH Targeted Fluorescent Liposome as Bimodal Nanoparticle for Drug Delivery and Optical Imaging.

S Khaleghi, F Rahbarizadeh, SK Nikkhoi
Journal Paper , , {Pages }

Abstract

PE38-based gene therapy of HER2-positive breast cancer stem cells via VHH-redirected polyamidoamine dendrimers

C Moradian, F Rahbarizadeh
Journal Paper , , {Pages }

Abstract

The Potential Applicability of Single-Domain Antibodies (VHH): From Checkpoint Blockade to Infectious Disease Therapy

P Safarzadeh Kozani, P Safarzadeh Kozani, F Rahbarizadeh
Journal Paper , , {Pages }

Abstract

Optimizing the Clinical Impact of CAR-T Cell Therapy in B-Cell Acute Lymphoblastic Leukemia: Looking Back While Moving Forward

PS Kozani, PS Kozani, F Rahbarizadeh
Journal Paper , , {Pages }

Abstract

Camelid Single-Domain Antibodies for Targeting Cancer Nanotheranostics

S Khaleghi, S Khoshtinat Nikkhoi, F Rahbarizadeh
Journal Paper , , {Pages }

Abstract

The Potential Applicability of Single-Domain Antibodies (VHH): From Checkpoint Blockade to Infectious Disease Therapy

PS Kozani, PS Kozani, F Rahbarizadeh
Journal Paper , , {Pages }

Abstract

Phospholipase-Cγ1 Signaling Protein Down-Regulation by Oligoclonal-VHHs based Immuno-Liposome: A Potent Metastasis Deterrent in HER2 Positive Breast Cancer Cells.

Ommolbanin Asadpour, Fatemeh Rahbarizadeh
Journal PaperCell Journal (Yakhteh) , Volume 22 , Issue 1, 2020 April 1, {Pages }

Abstract

Objective: The purpose of this study was to develop multivalent antibody constructs via grafting anti-HER2 antibodies, including Herceptin and oligoclonal-variable domain of heavy chain antibodies (VHHs), onto liposome membranes to enhance antibody activity and compare their effect on phospholipase C (PLC) signaling pathway with control. Materials and Methods: In this experimental study, SKBR3 and BT-474 cell lines as HER2 positive and MCF10A cell line as normal cell were screened with anti-HER2 antibodies, including constructs of multivalent liposomal antibody developed with Herceptin and anti-HER2 oligoclonal-VHHs. To confirm the accuracy of the study, immunofluorescent assay, migration assay and immuno-liposome binding ability to HER2 we

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