The physicians and nurses at the Institute for Pediatric Cancer and Blood Disorders are leading participants in clinical trials and research efforts of the
Children’s Oncology Group (COG). Treatment protocols coordinated by the Children’s Oncology Group are available for most children with cancer
treated at the Tomorrows Children’s Institute. Participation in these protocols enables our patients to receive cutting-edge oncology treatment.
Summary of Basic and Translational Research Related to Pediatrics Conducted in the Alice and David Jurist Institute for Research at HackensackUMC (2014)
Robert Korngold, Ph.D., Chairman, Department of Research, HackensackUMC
Amongst the twelve scientific laboratories that currently make up the Alice and David Jurist Research Institute at HackensackUMC,
there are three major projects that may eventually have an impact on improving outcomes in pediatric patients afflicted with blood cancers, brain tumors,
Type 1 diabetes, and alopecia areata. These projects are briefly described below.
Studies on the immunobiology of graft-versus-host disease and graft-versus-tumor responses. Robert Korngold, Ph.D., Senior Scientist,
Jenny Zilberberg, Ph.D., Assistant Scientist, Rena Feinman, Ph.D., Associate Scientist.
Allogeneic blood and marrow transplantation (allo-BMT) is an important therapeutic tool for the treatment of various types of leukemia,
as well as other hematologic disorders, and has potential for providing immunotherapy for several other forms of cancer.
Every year, hundreds of children with life-threatening disease undergo the procedure. One of the major complications of allo-BMT is
the development of graft-versus-host disease (GVHD) by which donor immune T cells in the graft recognize cells and tissues of the recipient as foreign and
attack them with often dire consequences. Thus, a basic understanding of the immune interactions and mechanisms of tissue damage in GVHD is essential
to developing ways to interfere with its development and in lowering the risks associated with allo-BMT. On the other hand, some donor T cells also
specifically attack residual recipient tumor cells in a graft-versus-tumor (GVT) response that can prevent relapse of the original cancer.
We are using molecular techniques to distinguish donor T cell responses that can cause GVHD from those that can mediate GVT, potentially allowing for
selective T cell manipulation of BMT grafts to improve disease-free survival of the recipients.
Studies on developing microfluidic devices for growing primary brain tumor tissues. Jenny Zilberberg, Ph.D., Assistant Scientist.
Despite being the most frequent solid malignancy in children, brain tumors are relatively rare and it is mainly for this reason that they have been a
somewhat low priority for research. Furthermore, while some patients can be considered cured after successful tumor resection, others will succumb to their
disease despite maximal multimodal therapy including surgery, radiation and chemotherapy. Unfortunately, it is highly unlikely that further dose escalation
or modification of chemotherapy regimens using traditional agents will drastically change outcome. In addition, side effects associated with radiation and other
therapeutic agents put this young population particularly at risk for severe long-term consequences, which ultimately impacts their quality of life; hence
the need to develop faithful tumor models that can highlight the personalized biology of each patient in order to evaluate best drug regimen at front,
to minimize toxicity and improve efficacy, and to establish novel therapeutic avenues in the relapse setting using patient specific samples. To this end,
Dr. Zilberberg and her collaborators in Pediatric Neurosurgery, along with colleagues at Stevens Institute of Technology in Hoboken, have been working on
designing a novel platform that uses microfluidic technology to preserve brain tumor cells in an in vitro culture system. The successful implementation of
this technology is expected to: 1) facilitate the study of this disease; 2) aid in the design of the optimum therapeutic avenues for these pediatric patients;
and 3) minimize treatment-associated toxicity by determining tumor susceptibility to a particular drug regimen prior to subjecting the patients to damaging chemotherapy.
Studies on the use of cord blood stem cells to immunomodulate type 1 diabetes and alopecia areata. Yong Zhao, M.D., Ph.D., Associate Scientist.
Type 1 diabetes (T1D) is an autoimmune disease that usually occurs in children and reduces their pancreatic islet beta cells and thereby limits insulin production.
Millions of individuals worldwide have T1D, and the number of children with diagnosed or undiagnosed T1D is increasing annually. Insulin supplementation is
not a cure. It does not halt the persistent autoimmune response, nor can it reliably prevent devastating complications such as neuronal and cardiovascular
diseases, blindness, and kidney failure. A true cure has proven elusive despite intensive research pressure over the past 25 years. Alopecia areata (AA) is
another one of the most common T cell-mediated autoimmune skin diseases, with chronic and relapsing hair loss. AA affects both children and adults at all ages
and on hairs of all colors, with a prevalence rate at 2% of the overall population without gender predilection. Clinical evidence supports a high prevalence of
comorbid autoimmune conditions among individuals with AA, such as thyroid disease, type 1 diabetes mellitus, inflammatory bowel disease, and systemic lupus
erythematosus. The quality of life in AA patients have been significantly affected by the disappointing outcomes, side effects, and relapses with current
conventional therapies. Notably, Dr.Zhao and his team have successfully developed a groundbreaking technology termed Stem Cell Educator therapy, based on the
discovery of a particular type of stem cell found in umbilical cord blood that has the capacity to alter autoimmune cells so that they no longer can mediate
disease. To date, clinical trials in adult patients have demonstrated the safety and efficacy of the Stem Cell Educator therapy for the treatment of T1D and
alopecia areata. Here, we intend to reproduce those findings in pilot clinical studies at HackensackUMC and then evaluate the safety and efficacy of the
Stem Cell Educator therapy in children with Type 1 diabetes and alopecia areata. At the same time, Dr. Zhao and colleagues are trying to understand the
mechanism of action of the cord blood stem cells upon autoimmune cells.