Absence of GIPSITUMABTM A Newly Discovered Bispecific Naturally Occuring IgA/IgG Heterodimer Portends the Existense of a Genetic Cancer/Infections Risk Marker Found in Two Subjects of African-American Lineage

Padmanabhan Nair

Johns Hopkins University Bloomberg School of Public Health, USA

We had previously reported the discovery of a broad-spectrum antibody generated naturally by cells lining the wall of the human large bowel that kills a variety of cancer cells. This antibody, GIPSITUMABTM is a chimeric heterodimer of IgA/IgG. This bivalent immunoglobulin has two arms, one IgG binding to a common membrane-associated tumor antigen (MATATM) resulting in osmolytic tumor cell death while the other arm (IgA) is postulated to recognize cells infected by pathogenic viruses/bacteria resulting in destruction of the infected cells.

In a cohort of about 60 normal free-living subjects, we isolated these exfoliated colonocytes from small aliquots of stool (0.5 gms) using our SCSR technology. They were then labelled with fluorescent tagged antibodies to IgA/ IgG and analyzed by flow cytometry to detect the coexpression of the chimeric GIPSITUMABTM. We found two subjects in this group without any evidence of this chimera. On further unblinding the dataset, we were surprised to find that these two subjects were of AfricanAmerican ethnicity.

We have now developed a simple two step procedure to transform these colonocytes into antibody secreting cell lineage similar to monoclonals. This process of generating this native antibody (oncolytic or therapeutic for infectious diseases such as HIV, ebola, anthrax, malaria, influenza) is superior to hybridomas and is significantly cost effective, estimated at about 12% of what is currently costing.

Proof of concept studies have shown this novel antibody to be controlled at the genomic level and therefore its absence in humans is postulated to be a germ-line deletion resulting in a genomic syndrome probably associated with increased risk of developing a malignancy or contracting an infection.

This is a first in class bispecific naturally-occurring antibody with therapeutic properties.

Supported by the National Institutes of Health, SBIR Grants, Phase I and II R44CA81799 and R44DK56567

Biography:
Padmanabhan Nair, Ph.D., FAAAS was in Singapore. His education was B.Sc. (1946) from University College, Travancore University, Trivandrum, Kerala, India. After his M.Sc, (1954) Ph.D. (1956) Royal Institute of Science, Mumbai, India. Later he started Research Officer, (1958-1960) All-India Institute of Medical Sciences, New Delhi, India; Fulbright Scholar and McCollum-Pratt Fellow,(1960-19963) The Johns Hopkins University, Baltimore, Maryland; Head of Medical Research,(1963-1983) Sinai Hospital of Baltimore, Inc; Research Scientist (1983-1998), Fellow, American Association for the Advancement of Science, Beltsville Human Nutrition Research Center, ARS, USDA, Beltsville, Maryland; Founding President and CEO, (2000) NonInvasive Technologies LLC, Elkridge, Maryland; Adjunct Professor of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, Roll of Honor, Institute of Science, Bombay declared by the Hon. V. V. Giri, President of India.

Advances in the Pathology and Genetics of Pediatric Cancer

Atif A. Ahmed

Childrenʼs Mercy Hospital and University of Missouri, USA

Recent advances in molecular diagnostics that can analyze the tumorʼs genetic make-up have provided greater understanding of pediatric cancers. Pediatric malignancies are much rarer and different from adult tumors, in their histology, molecular pathogenesis and response to treatment. They are more often induced by inherited or sporadic errors in development rather than by environmental exposure. The landscape of genomic alterations in pediatric cancer shows significant differences from adult cancers in terms of mutation frequency and type of altered genes. Childhood malignancies have a relatively high prevalence of specific structural variations (e.g., gene fusions and chromosomal rearrangements) and exhibit high specificity ofassociations with histologic tumor subtypes. Pediatric tumors have a fewer number of actionable targets than adult tumors, thus potentially limiting the utility of precision oncology in children. The use of next-generation sequencing (NGS) methods coupled with limited morphologic classification has offered better insight into the diagnosis, prognosis and practical clinical management of patients, and obviated the need for extensive immunohistochemical and molecular tests. Molecular classification of tumors has replaced extensive histologic subtyping and has provided better prognostic information for patients.

Biography:
Atif A. Ahmed is Professor of Pathology and Director of the Anatomic Pathology Division at Children's Mercy Hospitals, Kansas City, Mo, USA. Dr. Ahmed is a board-certified pathologist, graduated from Medical School in 1988, completed pathology residency and fellowship training in the U.S.A. and has been in academic practice for more than 15 years. His research interests include pediatric tumor biology and targeted biomarkers in cancer. Dr. Ahmed published more than 90 publications including peer-reviewed articles, book chapters and meeting abstracts. He is the book editor of "Gastrointestinal Stromal Tumors in Adults and Children" and “Anatomic and Clinical Pathology Board Review”. He is a Member of the Society for Pediatric Pathology, the Children's Oncology Group, and the American Association for Cancer Research; a Life Fellow of the College of American Pathologists; and an overseas fellow of the Royal College of Pathologist [UK]. He serves on the editorial board of several journals.

Psychological Correlates of Cancer Survival

Shulamith Kreitler

Tel-Aviv University, Israel

The purpose was to define psychological variables that support cancer survival. The theoretical approach was based on the cognitive orientation health model (Kreitler & Kreitler) which assumes that the chances for survival are a function of several factors in addition to medical treatment. Psychological factors are one kind of these factors that may promote survival. The methodology of identifying the relevant psychological factors will be described as well as the themes it produced that were summarized in the form of a questionnaire. The questionnaire of the cognitive orientation of survival included statements referring to beliefs about oneself, about others and reality, about rules and norms and about goals and wishes. The questionnaire was administered to cancer patients with three different diagnoses (breast, melanoma, colorectal) in the first phase of their medical treatment and they were checked again after 5 years and then again after 12 years. The dependent variables in the conducted regression analyses were disease-free survival, metastases, new cancers, no-survival. The results provided information about the relevant psychological correlates of the different kinds of survival.

Biography:
Shulamith Kreitler has graduated in psychology and psychiatry at Bern University, Switzerland. She has been a full professor of psychology at Tel Aviv University since 1986, has worked at the universities of Princeton, Harvard, Yale University, Vienna and Buenos Aires. She is a certified clinical psychologist and health psychologist. She has established the psychooncology unit (Ichilov) and the Center for Psychooncology Research (Sheba Medical Center). She has developed a new approach to meaning,to predicting and changing behaviorand identifying psychological risk factors for cancer. She has published over 200 articles and 18 scientific books and is preparing a book about psychooncology (Springer).