Emerging Collaborations and Future Plans
Tissue Engineering and Regenerative Medicine
In 2004, Anthony Atala, MD, an internationally recognized pioneer in tissue engineering and regenerative medicine, was recruited to Wake Forest as Chairman of the Department of Urology and Director of the Wake Forest Institute of Regenerative Medicine. The oncologic applications of this novel and exciting area of science was a primary motivator for Dr. Atala’s recruitment. The following section summarizes the Cancer Center’s future plans for tissue and cellular engineering and regenerative medicine in oncology, with the major areas of interest being organ reconstruction, tumor microenvironment, and angiogenesis.
Unfortunately, multidisciplinary cancer treatment often leads to organ damage or loss, requiring eventual reconstruction. The potential of regenerative medicine focuses on new approaches to repairing and replacing cells, tissues and organs. Technologies for engineering tissues are developing rapidly, with the ultimate goal of delivering new therapies as safely and efficiently as possible. As a cancer therapy, we propose to use tissue engineering to engineer tissue and organs such as bladder, vessel, cartilage, skin, bone, kidney, muscle, and salivary gland for replacement in cancer patients. We aim to create more efficient ways to enhance cell growth and function in vitro, and to develop ideal three-dimensional scaffolds that will allow engineered tissues to mimic tissue and organ function while ensuring long-term survival of the engineered tissues. The projects will be performed by interactions between scientists in the fields of biomedical and chemical engineering, cell and molecular biology, biochemistry, physiology, materials science, nanotechnology, genomics, proteomics, drug delivery, surgery and medicine.
Tumor microenvironment and angiogenesis represent yet another linkage between the Cancer Center and Institute for Regenerative Medicine at Wake Forest. Implantation into tumors of microencapsulated engineered cells that secrete molecules with a therapeutic index is a novel approach to cancer gene therapy. For the treatment of cancer, we propose a cell-based cancer therapy where encapsulated genetically modified cells overexpress therapeutic proteins when implanted near solid tumors. The proteins secreted by cells are diffused through the microcapsule membrane to exert therapeutic effect in vivo. We have shown that microencapsulated engineered cells by alginate based polymers released endostatin for an extended period and successfully inhibited tumor vessel formation. In anticipation of clinical application for therapy of a variety of tumor types, we aim to construct a cell microencapsulation system to enable cell transplantation without major invasive surgery.
Nanotechnology and Molecular Materials
The National Cancer Institute has recently established the application of nanotechnology to cancer imaging and therapeutics as an important priority. The presence of a Nanotechnology Center at Wake Forest University under the direction of Dr. David Carroll, a member of the Clinical Research Program as well as the Cancer Center’s IAB, facilitated the entry of the CCCWFU into this field in late 2004. Dr. Carroll, with Dr. Steve Akman, Director of the Breast Center of Excellence, are starting a number of cancer nanotechnology initiatives, first in breast cancer, but expanding to the other major foci of our Center including prostate and brain cancer. Future plans for nanotechnology and molecular materials research includes the following:
- Creation of iron and nitrogen-doped carbon nanorods to efficiently capture long wavelength electromagnetic radiation, dissipating the energy as tumoricidal heat
- Identification of iron-doped carbon nanorods as MRI imaging agents, since iron couples to protons to affectT2 weighted images
- Covalent coupling of antitumor agents such as doxorubicin, to fullerenes and carbon nanorods as a novel drug delivery system
- Study of interaction between hydrophobic fullerenes and carbon nanorods with apolipoprotein B-HER2protein fusion constructs for the targeted delivery of nanostructures to cancer cells.
We expect that these projects will mature with respect to grant funding and publications over the next few years. The Cancer Center, and in particular the Clinical Research Program (therapeutic modulation and bioanatomic imaging themes) will play a key role in facilitating research in these exciting areas.
The Virginia Tech – Wake Forest Collaboration in Cancer
In 2002, Wake Forest University and the Virginia Polytechnic Institute (Virginia Tech) formed a School of Biomedical Engineering. Shortly thereafter, several faculty exchanges took place between the two Institutions. In his Director's overview, Dr. Torti has described the emerging collaborations between the Cancer Center and Virginia Tech. Among them is a collaboration between the Cancer Center's Clinical Research Program and the Virginia Tech School of Veterinary Medicine's Center for Comparative Oncology (CeCO). Their particular area of mutual interest is in two solid tumors of neuroectodermal origin, malignant glioma and cutaneous melanoma, both of which spontaneously occur in humans and animals. Through the use of Cancer Center pilot funds, three joint projects are ongoing: 1) Histologic, genetic, and molecular similarities between human and canine malignant astrocytoma, 2) Treatment of canine malignant astrocytoma with surgical resection followed by recombinant cytotoxin therapy with IL13-PE, utilizing convection enhanced delivery, and 3) Treatment of equine cutaneous melanoma with frankincense, an essential plant oil. Participants in these collaborations include John Robertson, D.V.M, Ph.D., Director of the CeCO and John Rossmeisel, D.V.M, veterinary neurosurgeon from Virginia Tech, and from Wake Forest, Waldemar Debinski, M.D., Ph.D. and Edward Shaw, M.D., (Clinical Research Program), Jianfeng Xu, Ph.D., (Cancer Control Program), and Costas Koumenis, Ph.D., (Cell Growth and Survival Program). As pilot data are generated from the Cancer Center funded pilot studies, joint Virginia Tech – Wake Forest NCI grants will be submitted.