Program

Swapna Chaudhuri

Title: The Immunotherapeutic Potential of the Novel Biomolecule T11 Target Structure

Plenary

Swapna Chaudhuri

Chittaranjan National Cancer Institute, India

Abstract

T11TS is a novel bimolecular therapeutic probe, the disease relevance of which has been worked out for the first time in our laboratory. Recently a patent has been granted on this score.

Main bulk of the work has been done on experimental glioblastoma, the most fatal of all brain tumors despite therapeutic advances. T11TS was isolated, characterised and proved to ameliorate experimental glioma by multimodal mechanistic activities. Usually a specific molecular therapy acts in a specific pathway, but contrary to this T11TS acts as a multi-edged sword intervening each of the pathways like Immune Potentiation, Alteration of Cytokine Levels, Specific Apoptotic Induction, Cell Cycle Modulation, Anti-Angiogenesis. 

T11TS immunotherapy in glioma reverses immunosuppression and causes profound immunepotentiation both at the peripheral and intracranial levels. Complete downregulation of T-cell signaling in glioma was reversed by T11TS. T11TS also modulated cytokine levels favoring specific apoptotic killing of glioma cells. T11TS intervention was also studied molecularly at hematopoietic stem cell (HSC) level. 

As an Immunotherapeutic agent T11TS was effective against other cancers like Arsenic induced cancer in mouse model, canine pyoderma and canine demidocosis. Our recent studies have proved that T11TS was very effective in complete destruction of Cryptococcus neoformans in rat model, exciting both the Innate and Adoptive Immune system.

Toxicity studies with T11TS revealed that it is totally nontoxic. T11TS acting as an ideal Immunotherapeutic agent act not only as an Anti-neoplastic agent, but also against other diseases. The above studies pave the way for translational research with T11TS.

Biography

Presently working as Emeritus Medical Scientist, ICMR, Prof Swapna Chaudhuri was the former Professor and Head, Department of Laboratory Medicine, Calcutta School of Tropical Medicine. Worked as a Scientist at the Royal Institute of Cancer Research, Surrey, UK. Her research area is in the field of Immunology and Immunotherapy of Cancer; Pollen induced allergy and asthma; Fungal Infection and Hematopoietic Stem cell. Taught at both Postgraduate and Undergraduate levels. Published seventy five papers in peer reviewed journals and also reviews, monograms, book chapters. Has won many Academic laurels and Fellowships, affiliated to twelve Academic Societies, Associate Editor of International journals, Reviewer of 68 high impact factor journals, Principal Investigator of twenty one projects, Supervised 25 PhD, MD and DM students.

Charles J Malemud

Title: Tofacitinib Inhibits Interleukin-6-induced STAT Phosphorylation and Matrix Metalloproteinase Gene Expression in C28/I2 and Normal Human Chondrocytes

Charles J Malemud

Case Western Reserve University, USA

Abstract

Rheumatoid arthritis (RA) is characterized, in part, by destruction of articular cartilage by matrix metalloproteinases (MMPs) in response to pro-inflammatory cytokines, such as interleukin-6 (IL-6), a potent activator of JAK-STAT signaling. Tofacitinib a pan-Janus kinase inhibitor,and USFDA-approved for treating RA was employed to determine the extent to which inhibition of STAT protein phosphorylation was accompanied by suppression of matrix metalloproteinase (MMP) gene expression. C28/I2 chondrocytes, used as a surrogate for normal chondrocytes, or normal human chondrocytes (NHC) were grown to high-density confluencyand treated with recombinant human interleukin-6 (rhIL-6) (20ng/mL) for up to 60 min. Activation of STAT proteins was determined by quantifying anti-STAT1, -3, or -5AB immunoblots. C28/I2 chondrocytes produced STAT1, STAT3 and STAT5AB whereas NHC produced only STAT1 and STAT3. Unexpectedly treatment of NHC with rhIL-6 increased the content of total STAT1, STAT3 and, in several cases total STAT content was reduced by tofacitinib. STAT1 and STAT3 were phosphorylated following incubation of NHC with rhIL-6 after 30 min as was STAT1, STAT3 and STAT5AB by rhIL-6-treated C28/I2 chondrocytes. Pre-incubation of C28/I2 chondrocytes or NHC with tofacitinib (2.5nM-100nM) for 30 min followed by rhIL-6 andtofacitinib for an additional 30 min caused a statistically significant decrease in p-STAT1 and p-STAT3. Moreover, tofacitinib reduced MMP-3 and MMP-13gene expression, but not MMP-1, -2 or -9gene expression. These results may have relevance in the context of correcting the altered integrity of articular cartilage associated with chronic synovial joint inflammation and the elevated level of IL-6 characteristic of RA. 

Biography

Charles J. Malemud received the Ph.D. from George Washington University and did his post-doc at the State University of New York (Stony Brook, NY). He is on the faculty at Case Western Reserve University School of Medicine where he is Professor of Medicine & Anatomy in the Division of Rheumatology and Chair of the Fellowship Research Committee. He has published over 275 papers, book chapters, commentaries and, reviews primarily in the field of chondrocyte biology. Dr. Malemud is on the editorial board of several journals and is Editor-in-Chief of the Journal of Clinical and Cellular Immunology, and Current Rheumatology Reviews.

Jing H Wang

Title: MHC Class-I independent activation of virtual-memory CD8 T cells induced by chemotherapeutic agent-treated cancer cells

Jing H Wang

University of Colorado Anschutz Medical Campus, USA

Abstract

Cancer cells can evade immune recognition by losing major histocompatibility complex (MHC) class I. Hence, MHC class I-negative cancers represent the most challenging cancers to be treated.  Chemotherapeutic drugs not only directly kill tumors but also modulate tumor immune microenvironment.  However, it remains unknown whether chemo-treated cancer cells can activate CD8 T cells independent of tumor-derived MHC class I and whether such MHC class I-independent CD8 T cell activation can be exploited for cancer immunotherapy.  Here, we showed that chemo-treated cancer cells directly activated CD8 T cells in an MHC class I-independent manner and that these activated CD8 T cells exhibit virtual memory (VM) phenotypes. Consistently, in vivo chemotherapeutic treatment preferentially increased tumor infiltrating VM CD8 T cells. Mechanistically, MHC class-I-independent activation of CD8 T cells requires cell-cell contact and the activation of PI3K pathway.  VM CD8 T cells contribute to a better therapeutic effect on MHC class I-deficient tumors.  Using humanized mouse models or primary human CD8 T cells, we also demonstrated that chemo-treated human lymphomas activated VM CD8 T cells independent of tumor-derived MHC class I.  In conclusion, CD8 T cells can be directly activated in an MHC class-I-independent manner by chemo-treated cancers, and these activated CD8 T cells may be exploited for developing new strategies to treat MHC class I-deficient cancers.

Biography

Dr. Jing Hong Wang, M.D., Ph.D., is an Associate Professor in the Department of Immunology and Microbiology at the University of Colorado School of Medicine at Anschutz Medical Campus (https://medschool.cuanschutz.edu/immunology-and-microbiology/faculty/wang). Dr. Wang graduated from Beijing Medical University (now known as Peking University Health Science Center) with a M.D., Ohio State University with a M.S. and University of Chicago with a Ph.D. Dr. Wang completed postdoctoral fellowship at Children’s Hospital in Boston. Dr. Wang joined her department in 2011 as an Assistant Professor and was promoted to Associate Professor in 2016. Her research program is currently supported by multiple NIH grants.

Leitzke Marco

Title: Autonomic balance determines the severity of COVID-19 courses

Leitzke Marco

Helios Clinics Germany

Abstract

COVID-19 has left mankind desperately seeking how to manage dramatically rising infection rates associated with severe disease progressions. COVID-19 courses range from mild symptoms up to multiple organ failure and death, triggered by excessively high serum cytokine levels (IL 1β, IL6, TNF α, IL8). The vagally driven cholinergic anti-inflammatory pathway (CAP) stops the action of nuclear factor κB (NF-κB), the transcriptional factor of pro-inflammatory cytokines. Thus, well-balanced cytokine release depends on adequate vagal signaling. Coronaviruses replicate using NF-κB transcriptional factor as well. By degrading the cytoplasmatic inhibitor of NF-κBsubunits (IκB), coronaviruses induce unrestricted NF-κB expression accelerating both, virus replication and cytokine transcription.

We hypothesize that CAP detriment due to depressed vagal tone critically determines the severity of COVID-19.

 

Biography

Shyamapada Mandal

Title: Perspectives to the COVID-19 immunopathology and vaccine status

Shyamapada Mandal

University of Gour Banga, India

Abstract

The coronavirus disease 2019 (COVID-19) pandemic, since its first emergence in China in December 2019from SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection, caused more than103 million people sick with2,237,636 deaths globally, as of February3, 2021. The highly infectiousBetacoronavirus, SARS-CoV-2,replicates inthe upper respiratory system at the disease initial stage (causing mild or asymptomatic COVID-19 in most cases), followed by immunopathological stage of inflammatory response to SARS-CoV-2 infection causing severe/criticalCOVID-19 with cytokine storm (a stage with substantial elevation of serum pro-inflammatory cytokines levels) and ARDS(acute respiratory distress syndrome) and multiple organ failure (majorly lungs, as well as heart, liver and kidney). However, no specific drug or vaccine is available to effectively combat theCOVID-19 pandemicthat devastated the most vulnerable (people of old age, or with medical conditions). Vaccine is therefore urgently required to prevent SARS-CoV-2 transmission, and deaths due to COVID-19. This communication thus stands for analysis (based on the available published information) withanupdateof the vaccinesthat are in the pipeline of rapid pace of COVID-19vaccine development. 

Biography

Dr. Shyamapada Mandal, Professor, Department of Zoology, University of Gour Banga, India, is interested re-PhD, PhD, and post-PhD research under the guidance of Professor Nishith Kumar Pal at Calcutta School of Tropical Medicine, India. He has published 115 articles with seven book chapters. He is life member of IAMM and IASR, India, and fellow member of SASS, India. Eight national academic and research awards have been conferred to him. He has guided 52 post graduate students; supervised three MPhil and three PhD students, and supervising 6 PhD students. Professor Mandal is among the world’s top 2% scientists as per the survey of the Stanford University, published in PLOS (Public Library of Science) Biology (October, 2020).

Demmouche Abbassia

Title: Evaluation of The curative role, Anti-inflammatory and anti-oxidative activity of some dietary spices on carrageenan induced paw edema in albino Wistar rats

Demmouche Abbassia

University Sidi Bel Abbes, Algeria

Abstract

Background: Inflammation is a response of the immune system, guarding the individual against infection. It is a major burning problem worldwide and billions of individuals are affected. Some of the spices used daily in Algerian cuisine have been known to possess major anti-inflammatory effects. Turmeric, red pepper, ginger, cinnamon and cumin  etc. are a few of the wide spectrum of spices used in Algeria.

The aim of the study was to investigate the antiinflammatory effect  and anti actvity of some dietary spices in carrageenan induced models of inflammation on Wistar  rats.

Methods: Albino wistar rats were divided into four groups. Inflammation was induced on the animal by injecting the right hand paw with carrageenan (0.1 ml of 1%). Group 1  was fed with food and water and  treated with carrageenan (control) whereas group 2 and  3 treated with different doses (100 and 200 mg/kg/bw) of aqueous extract of some dietary spices with carrageenan, respectively. Group 4 treated with standard drug diclofenac sodium (10 mg/kg b.w., reference drug for inflammation), once for 24 hrs.

Results:

The content of total phenolic was 137.2±21.6 mg/g and flavonoids 122.3±5.8 mg/g. After 60, 120, 180, 240 and 300 min, the data indicate that  some dietary spices 100 and 200 mg/kg was significantly effective reducing paw edema volumes induced by carrageenan compared to control (p <0.01). The levels of serum pro-inflammatory white blood cells, neutrophile, lymphocyte, monocyte, eosinophile, total protein and protein c reactive and total cephalin KADIN  and platelts in the control group were significantly increased by carrageenan injection compared with the normal group. The rats pretreated with some spices 100 and 200 mg/kg had significantly lower levels of pro-inflammatory to compare control group.

The paw edema in carrageenan-induced rats was considerably reduced by treating with 100 and 200  mg/kg aqueous extract of some dietary spices when compared to the untreated rats (p<0.001).

Conclusion : The present results clearly demonstarted that carrageenan significantly increased paw edema whereas some dietary treated rats significantly decreased the paw edema. The study underlines the importance of some of the frequently used spices (Turmeric, red pepper, ginger, cinnamon and cumin)  in the treatment of inflammation.

 

Biography

Alexander Ariel Padron Gonzalez

Title: Neurolimmunological manifestations to dengue virus

Alexander Ariel Padron Gonzalez

Medicin Inmunologist, Cuba

Abstract

Introduction: Neurological manifestations associated to dengue virus are being reported more frequently.
Objective: To identify the neuroimmune response evaluated by Reibergram in patients with neurological manifestations because of dengue virus.
Material and methods: The highest levels of immunoglobulin and albumin were quantified in serum and the cerebrospinal fluid in six adult patients with neurological manifestations of dengue. Q function was calculated with the concentration values in serum and cerebrospinal fluid of these analytes. Values of immunoglobulin Q vs Q albumin were introduced in the specific Reibergrams for each immunoglobulin. Albumin was used as a marker for the evaluation of Blood-Cerebrospinal Fluid barrier.
Results: Reibergram allowed to establish the incidence of intrathecal synthesis of higher immunoglobulins (three types of patterns) in both the postinfectious and parainfectious neurological manifestations, except a patient who developed Guillain-Barre Syndrome. It also allowed to evaluate the blood-cerebrospinal fluid barrier in each patient. 

Conclusions: The use of Reibergram is important in the assessment of the immune response in patients with neurological manifestations of dengue virus.
 

Biography

Eswari Beeram

Title: Characterisation and purification of RNase A from Rat testes and long term effects of metosartan on male fertility

Eswari Beeram

Sree Vidyanikethan Degree College, India

Abstract

Ion exchange chromatography and chromatofoccusing serve as two important techniques used to isolate proteins based on the PH. RNaseA has an isoelectric PH of 9.6 where as testicular characterisation of RNase By HPLC and chromatofocussing proved to contain two RNases in which one of the RNase has similar structure and isoelectric PH similar to standard RNaseA. The molwt. of the RNase A in rat testes was found to be about 24kd determined by MALDI- TOF.Long term treatment of rats with metosartan does not shown effect on histology of rat testes but elevated apoptosis in rat testes and epididymal sperms. Affect of metosartan on weight of testes was not satisfactory but some what significant.

 

Biography

Eswari beeram is currently working as a Assistant Professor in Sree Vidyanikethan Degree College and she is engaged mainly in research on drug metosartan.

Antongiulio Demonte

Title: Hydroxichloroquine-induced Steven Johnson Syndrome. A case report

Antongiulio Demonte

Ospedale G. Da Saliceto, U.O. di Allergologia

Abstract

Background

Systemic lupus erythematosus (SLE) isan autoimmune disease with a multiple organsinvolvement. SLE pathogenesisissustained by innate and adaptive immune systemdisregulation, complementactivation, immune complexes, and tissueinflammation. The pattern of clinicalmanifestationsisheterogenous and changes over time.

Hydroxychloroquine (HCQ)isprimarydrug in the treatment of SLE. Itmodulates the immune response by inhibiting B cellreceptor and TLR signaling and activation (1).

Clinical Case

Thisis a case report of a 61 yearsoldfemaleaffected by SLE with recurrentoralaftosis, Lupus anticoagulantantibodies and previouspleuritis in remission.

The patienthad a long course treatment with low dose oralcorticosteroids (5 mg prednisone) and HCQ from three weeks.

After 20 days of treatment with HCQ shedeveloped an abruptcutaneousmanifestationconsisting in painful and infiltratingpapulesraised over the uppertrunk and limbs, rednessscaleslesions to palm and soles, lipswelling,painfulconjunctivitis and milddisphagia.

Slowly progressive improvement of cutaneous and mucosalsignswasobservedafterdrugdiscontinuation,twodaysafterappearance of clinicalmanifestations, andintroducing medium-high dose oforalcorticosteroidstherapy.

Results

Clinicalexams, performed in acute phasehighlighted a markedlymphocytopenia and raised of Reactive C Protein (RCP).Nicolskysignwasslightly positive.

Afterdiscontinuation of HCQ the patientdidnot show cutaneous or infectivesequelae due to promptidentification of Steven-Johnson Syndrome (SJS).

The patientreplaced HCQ with increasing of mainteinance dose of oralcorticosteroids.

Skintestswerenotperfomedfor therisk of SJS exacerbation and concomitantcorticosteroidstherapy. 

Conclusions

Like allmedications, HCQ has side effects and mayoccur in autoimmune diseasepatients. The mainundesirableeffectsobserved are digestive disorders and skinmanifestations.

Althoughskindisease are common side effects of HCQ severe toxidermiais a rare conditiondescribed in few case reports of DRESS and SJS (2-4).

Despite the rare occurrence of thesereactions, weobservedothercases of toxidermiaduring the pandemicbreakthrough in Italywhen HCQ waswidelyused for teratment of COVID-19.

References:

  1. Fava a, Petri M. Systemic Lupus Erythematosus: Diagnosis and Clinical Management J Autoimmun. 2019 Jan; 96: 1–13.
  2. Davoodi L, et al. Hydroxychloroquine-induced Stevens–Johnsonsyndrome in COVID-19: a rare case report. Oxford Medical Case Reports, 2020;6,193–195
  3. Idoudi S et al.Toxidermies à l’ hydroxychloroquine :à propos d’une sériehospitalière. La Revue de médecine interne 40 (2019) A105–A214
  4. Volpe A, Marchetta A, Cremaschi P et al. Hydroxychloroquine-induced DRESS syndrome. ClinRheumatol (2008) 27:537–539

Biography

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