Discovery and preclinical development of a therapeutically active nanobody-based chimeric antigen receptor targeting human CD22.

Chimeric antigen receptor (CAR) T cell therapies targeting B cell-restricted antigens CD19, CD20, or CD22 can produce potent clinical responses for some B cell malignancies, but relapse remains common. Camelid single-domain antibodies (sdAbs or nanobodies) are smaller, simpler, and easier to recombine than single-chain variable fragments (scFvs) used in most CARs, but fewer sdAb-CARs have been reported. Thus, we sought to identify a therapeutically active sdAb-CAR targeting human CD22.

Urine Tenofovir Levels Strongly Correlate With Virologic Suppression in Patients With Human Immunodeficiency Virus on Tenofovir Alafenamide-Based Antiretroviral Therapy.

We found that urine tenofovir (TFV) levels >1500 ng/mL strongly predict virologic suppression among people with human immunodeficiency virus taking tenofovir alafenamide (odds ratio, 5.66; 95% confidence interval, 1.59-20.

Masking terminal neo-epitopes of linear peptides through glycosylation favours immune responses towards core epitopes producing parental protein bound antibodies.

Glycosylation of hydrophobic peptides at one terminus effectively increases their water-solubility, and conjugation through the opposing end to a carrier protein, renders them more immunogenic. Moreover, the glycosylation minimizes antibody responses to potentially deleterious, non-productive terminal neo-epitope regions of the peptides, and consequently shifts peptide immunogenicity towards the core amino acid residues. As proof of concept, glycopeptide-protein conjugates related to influenza hemagglutinin (HA), neuraminidase (NA), and the dimerization loop region of human epidermal growth factor receptor 2 (Her2), demonstrated a favorable production of core peptide specific antibodies as determined by ELISA studies.

A High-Throughput Method for Characterizing Novel Chimeric Antigen Receptors in Jurkat Cells.

Chimeric antigen receptor (CAR) development involves extensive empirical characterization of antigen-binding domain (ABD)/CAR constructs for clinical suitability. Here, we present a cost-efficient and rapid method for evaluating CARs in human Jurkat T cells. Using a modular CAR plasmid, a highly efficient ABD cloning strategy, plasmid electroporation, short-term co-culture, and flow-cytometric detection of CD69, this assay (referred to as CAR-J) evaluates sensitivity and specificity for ABDs.

Evaluation of recombinant adenovirus vectors and adjuvanted protein as a heterologous prime-boost strategy using HER2 as a model antigen.

Induction of strong antigen-specific cell-mediated and humoral responses are critical to developing a successful therapeutic vaccine. Herein, using HER2 as a model antigen, we aim to evaluate a therapeutic vaccine protocol that elicits anti-tumor antibody and cytotoxic T cells to HER2/neu antigen. Replication-competent (ΔPS AdV) and non-replicating recombinant adenoviral vectors (AdV) expressing a rat HER2/neu (ErbB2) oncogene, were generated and compared for four different doses and over four time points for their ability to induce antigen-specific T and B cell responses in mice.

Modulation of Th17 and regulatory T-cell responses during murine pregnancy contributes to increased maternal susceptibility to Salmonella Typhimurium infection.

Problem: Salmonella Typhimurium (S. Tm) infection in pregnant mice results in massive placental infection, fetal loss, and exacerbated systemic infection. The Th17 host response can aid control of S.

Salmonella enterica serovar Typhimurium-induced placental inflammation and not bacterial burden correlates with pathology and fatal maternal disease.

Food-borne infections caused by Salmonella enterica species are increasing globally, and pregnancy poses a high risk. Pregnant mice rapidly succumb to S. enterica serovar Typhimurium infection.

Screening of rural children in West Bengal for fragile-X syndrome.

Background & Objective: Screening for Fragile X syndrome (FRAXA), the most common genetic cause for mental retardation (MR), has mostly been carried out among MR patients. The present study was conducted to find out prevalence of FRAXA amongst children residing in the rural areas of West Bengal.

Methods: Demographic details including age, sex, nutritional status as well as birth, medical, and developmental histories, were collected amongst rural children (n=38,803) of West Bengal, India, over three years (2004-2007).

Study on DBH genetic polymorphisms and plasma activity in attention deficit hyperactivity disorder patients from Eastern India.

Dysfunctions in the norepinephric pathway have been speculated in the etiology of attention deficit hyperactivity disorder (ADHD), a common problem for children. Synthesis of norepinephrine from dopamine is catalyzed by the enzyme dopamine beta-hydroxylase and numerous polymorphisms in the DBH gene have been found to exert their direct influence on the enzyme activity independently. In the present study association of ADHD with four genetic polymorphisms, DBH-STR, rs1611115, rs1108580, and rs2519152, was examined in subjects belonging to eastern India.

Correlation between cystathionine beta synthase gene polymorphisms, plasma homocysteine and idiopathic mental retardation in Indian individuals from Kolkata.

Deficiency in cystathionine beta synthase (CBS) enzyme sometimes leads to hyperhomocysteinemia/homocystinuria, conditions often associated with mental retardation (MR). In this investigation, association of idiopathic MR (IMR) with six CBS gene polymorphisms and fasting total plasma homocysteine (plHcy) was explored. Nuclear families with IMR probands (N=180) and control subjects (N=106) were recruited.

Screening for methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in Indian patients with idiopathic mental retardation.

Although genetic, nutritional, and environmental factors have been found to aggravate mental retardation in approximately 1% of individuals, no cause is known till date. In this study, two genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR), C677T (rs#1801133) and A1298C (rs#1801131), have been investigated in idiopathic mental retardation (IMR) subjects. Significantly higher frequency of the C677 allele was observed in IMR (n = 155; chi(2) = 5.

Lack of association between down syndrome and polymorphisms in dopamine receptor D4 and serotonin transporter genes.

Down Syndrome (DS) patients suffer from cognitive dysfunction, depression, hyperactivity, irritability etc. Dopamine (DA) and serotonin (5HT) are known to control cognitive and behavioral attributes. An increased number of the DA receptor 4 (DRD4) is detected in brain regions primarily involved in cognition.

MAOA promoter polymorphism and attention deficit hyperactivity disorder (ADHD) in indian children.

Attention deficit hyperactivity disorder (ADHD) is a highly disabling, early onset childhood neurobehavioral disorder with a higher occurrence in boys as compared to girls. Pharmacological and molecular genetic studies have revealed the influence of dopaminergic and serotonergic systems in the etiology of the disorder. Monoamine oxidase A (MAOA) is a mitochondrial enzyme that regulates the dopaminergic signals in the pre-synaptic region.

Cystathionine beta-synthase T833C/844INS68 polymorphism: a family-based study on mentally retarded children.

Background: Cystathionine beta-synthase (CBS) mediates conversion of homocysteine to cystathionine and deficiency in enzyme activity may lead to hyperhomocysteinemia/homocystinuria, which are often associated with mental retardation (MR). A large number of polymorphisms have been reported in the CBS gene, some of which impair its activity and among these, a T833C polymorphism in cis with a 68 bp insertion at 844 in the exon 8 is found to be associated with mild hyperhomocysteinemia in different ethnic groups.

Methods: The present study is aimed at investigating the association between T833C/844ins68 polymorphism and MR.

Association of dopamine D4 receptor (DRD4) polymorphisms with attention deficit hyperactivity disorder in Indian population.

Attention deficit hyperactivity disorder (ADHD) is a childhood onset neurobehavioral disorder. Several studies worldwide have implicated a possible association between ADHD and transmission of different polymorphisms of the dopamine D4 receptor gene (DRD4) in different ethnic groups. However, this is the first report on the transmission of different polymorphisms of DRD4 in Indian subjects.

Analysis of polymorphisms in the dopamine beta hydroxylase gene: association with attention deficit hyperactivity disorder in Indian children.

Objective: To study the association of Attention Deficit Hyperactivity Disorder (ADHD) and polymorphism in the dopamine beta hydroxylase (DBH) gene in Indian ADHD cases.

Subjects: Forty one ADHD cases were diagnosed as per the DSM-IV-TR criteria and evaluated by Conners Parents and Teachers Rating Scale and Wechslers Intelligence Scale for Children.

Methods: Genomic DNA was amplified for exon 2 *444g/a and intron 5 (Taq I) polymorphism in the DBH gene followed by restriction fragment length polymorphism (RFLP) analysis.