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Since the dawn of life, bacteria and phages are locked in a constant battle and both are perpetually changing their tactics to overcome each other. Bacteria use various strategies to overcome the invading phages, including adsorption inhibition, restriction-modification (R/E) systems, CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) systems, abortive infection (Abi), etc. To counteract, phages employ intelligent tactics for the nullification of bacterial defense systems, such as accessing host receptors, evading R/E systems, and anti-CRISPR proteins. Intense knowledge about the details of these defense pathways is the basis for their broad utilities in various fields of research from microbiology to biotechnology. Hence, in this review, we discuss some strategies used by bacteria to inhibit phage infections as well as phage tactics to circumvent bacterial defense systems. In addition, the application of these strategies will be described as a lesson learned from bacteria and phage combats. The ecological factors that affect the evolution of bacterial immune systems is the other issue represented in this review.

Introduction: Rheumatoid arthritis (RA), as one of the most disabling autoimmune diseases, is a common health problem that progressively reduces the life quality of patients. Although various biologics have been introduced for RA, attempts to establish an efficient long-term therapies failed due to the heterogeneity of this disease., Methods: In the last decade, immunomodulatory approaches such as T cell adoptive therapy have been developed for controlling autoimmunity. Regulatory T cells (Tregs), the major self-tolerance mediator, are crucial for down-regulation of aberrant immune stimulations. Hence, recruiting ex vivo Tregs emerged as a promising therapy for a variety of autoimmune diseases., Results: The major bottleneck of the Treg adoptive therapy is maintaining the in vivo stability and plasticity of these fascinating cells. Recent progress in genome editing technology clustered regularly interspaced short palindromic repeats (CRISPR) in combination with CRISPR-associated (Cas) 9 system provided a new solution for this bottleneck., Conclusions: The present paper discusses RA pathogenesis and the potential application of new developments in CRISPR-mediated Treg genome editing in personalized therapy of RA.

Immunotoxins are a novel class of cancer therapeutics that contains a cytotoxic agent fused to a targeting moiety. Various toxic agents from different sources are used in immunotoxin development, including bacterial, plant and human origin cytotoxic elements. Although bacterial and plant-derived toxins are highly toxic and commonly used in immunotoxins, their immunogenicity for human restricted their application in cancer therapy. Here, we discuss the advantages and limitations of bacterial toxins such as Pseudomonas and Diphtheria toxins, plant toxins such as ricin and gelonin, and some endogenous protein of human origin such as RNases and Granzymes. This article will also review different generations of immunotoxins with special focus on immunotoxins which are under clinical trials or approved for clinical use. Finally, current deimmunization strategies for development of new less-immunogenic recombinant immunotoxins will be discussed., Abbreviations: mAbs: Monoclonal antibodies; EF2: elongation factor 2; ITs: Immunotoxins; DT: Diphtheria toxin; PE: Pseudomonas exotoxin; dgA: de-glycosylated A-chain of ricin; rGel: recombinant de-glycosylated form of gelonin; NKC: natural killer cells; HTR: human transferrin receptor; EGF: epidermal growth factor; GM-CSF: granulocyte-macrophage colony-stimulating factor; DAB389: truncated Diphtheria toxin; B-CCL: B-cell chronic lymphocytic leukemia; RCC: renal cell carcinoma; GVHD: Graft-versus-host disease; EGFR: epidermal growth factor receptor; AML: acute myeloid leukemia; Fab: fragment antigen-binding; dsFv: disulfide-stabilized fragment variable; scFv: single-chain fragment variable; B-ALL: B-lineage Acute Lymphoblastic Leukemia; Fv: fragment variable; HCL: hairy cell leukemia; IL-2R: Interleukin-2 receptor; CR: complete response; CLL: chronic lymphocytic leukemia; ATL: adult T-cell leukemia; DARPins: designed Ankyrin repeat proteins; pmol: picomolar; HAMA: human-anti mouse antibody.

Phage display technology as a selection-based system is an attractive method for evolution of new biological drugs. Unique ability of phage libraries for displaying proteins on bacteriophage surfaces enable them to make a major contribution in diverse fields of researches related to the diagnosis and therapy of diseases. One of the great challenges facing researchers is the modification of phage display technology and the development of new applications. This article reviews the molecular basis of phage display library, and summarizes the novel and specific applications of this technique in the field of biological drugs development including therapeutic antibodies, peptides, vaccines, and catalytic antibodies.

Most B-cell-related disorders can be cured with conventional agents; however, relapse is common, creating a need for additional therapeutic options. In agreement, recent biomarker studies corroborate the role played by functional crosstalk between malignant B cells and microenvironment which have added texture to clinical outcome. Here we outline the essential role of the tumor-associated niche in B-cell Lymphoma/Leukemia pathogenesis, in an attempt to optimize the use of microenvironment-targeted drugs and anti-CD20 antibodies in the various subsets.

Objective: Rapid detection of mycobacterium tuberculosis (MTB) resistance is a key step in the control of disease. This study aimed to identify the prevalence and accuracy of isoniazid (INH) and rifampin (RMP) resistance and their risk factors using multiplex allele-specific polymerase chain reaction (MAS-PCR) to detect such mutations., Materials and Methods: In this cross-sectional study (2012-2013), 257 MTB patients from five frontier border provinces of Iran were selected and after divulging a full clinical history and undergoing a physical evaluation, the accuracy of drug resistance detection was carried out using the standard proportion test, sequencing, and GeneXpert/rifampicin (RIF) technique. Full demographic and environmental histories were evaluated., Results: The overall frequency of mutations was 34. Frequency of patients with mutations in KatG315 and at least one rpoB codon (of 516, 526, and 531 codons) were seven cases (2.7%). In comparison to the standard proportion test, the sensitivity and specificity of MAS-PCR in detecting common INH-resistant mutations were 68.75 and 100%, and in the detection of common RMP-resistant mutation were 81.8 and 100%, respectively. Also, 88.89% of KatG 315 mutations and 100% of rpoB mutations were diagnosed and compared with DNA sequencings. Compared to GeneXpert/RIF, 100% of RMP common point mutation was determined by MAS-PCR. Mutation odds were higher in males and greater in those with a history of anti-tuberculosis treatment., Conclusion: The results of this study indicated that MAS-PCR is an efficient method for rapid detection of mutations leading to RMP resistance but merely to KatG it is not satisfactory for the detection of INH resistance. Accurate and rapid detection of drug resistance is crucial in males and patients with a history of tuberculosis.

Recombinant antibodies are increasingly being employed as therapeutic agents especially in combination with anti-cancer drugs. The single-chain antibody fragments are small antigen-binding proteins which provide the most commonly used antibody formats for diagnostic and therapeutic purposes. These antibody fragments have more rapid tumor penetration and clearance from the serum relative to full-length monoclonal antibodies. There are in vitro antibody-display technologies such as phage display, cell surface display, ribosome display and mRNA display that can be used to isolate high specificity and affinity single-chain antibodies against a wide variety of targets. We review these strategies for generation of stable and active antibody fragments in the present article.