Contact the Group
(608) 265-9721 FAX
1111 Highland Avenue
Madison, WI 53705
Our team is pursuing novel, alternative approaches to treat childhood cancer. Our research includes areas such as adoptive immunotherapies, nano-oncology and stem cell graft design for the transplant setting.
γδ T Cells for Adoptive Cancer Immunotherapies
Cancer immunotherapy uses components of the immune system to fight cancer. It is a treatment modality which attempts to harness the immune system to recognize attack and kill malignant cells. Immunotherapies can consist of the administration of tumor-specific antibodies, cytokines, or the infusion or transfer of immune cells, such as Natural Killer (NK) cells or tumor-specific, genetically modified T cells such as chimeric antigen receptor-modified T cells (CARs), to name a few approaches.
A cell population our lab is specifically interested in using in the context of cancer immunotherapy is γδ T cells. γδ T cells only comprise about 3-6% of the human peripheral lymphocytes but are important for the primary response to infectious agents. We and others have shown that γδ T cells also have potent anti-leukemic and anti-tumor effects and appear to play a crucial role in cancer immunosurveillance. They can be significantly activated and expanded by amino bisphosphonates, such as zoledronate, and are being evaluated for anti-tumor effect in various cancer trials. Interestingly, γδ T cells do not cause graft-versus-host disease and seem therefore specifically suitable for autologous or allogeneic immunotherapy approaches. Our lab is therefore pursuing research with regards to the biology of γδ T cell activation, in vivo and ex vivo expansion and activation for use in adoptive cancer immunotherapies.
The evolution of nanotechnology offers a new dimension to tumor-targeting strategies. Gold (Au) and iron-based super paramagnetic iron-oxide nanoparticles (SPIO) have gained increasing interest for medical applications due to features such as unusual optical or magnetic properties, high stability and biological compatibility, controllable morphology and size dispersion, and chemical surface functionalization. One of the greatest promises of tumor-targeted Au and SPIO nanoparticles is their multifunctionality, i.e. the possibility of simultaneous imaging, drug delivery, and other therapeutic and diagnostic applications, such as localized hyperthermia elicited by alternating magnetic fields. For cancer treatment applications this approach requires either direct injection of particles into the tumor, or more practically and elegantly, the use of molecular probes, such as antibodies, that specifically guide the nanoparticles to the cancerous cell.
However, this new scientific frontier faces many challenges and there are numerous hurdles that need to be overcome prior to clinical application. For instance, many tumors lack suitable antigenic epitopes that allow for exclusive targeting. Phagocytosis and clearance of nanoparticles by macrophages and the reticuloendothelial system impairs targeting efficacy. For many particle types there is a lack of long-term toxicity data.
Our team’s initiative is to develop a nanotechnology-based platform to treat pediatric cancers, specifically neuroblastoma, which is one of the most common pediatric solid tumors with a high mortality rate in advanced-stage disease. Our team is evaluating anti-GD2 antibody-conjugated SPIO nanoparticles to specifically target neuroblastoma. We are investigating the optimal conditions (such as particle size, particle surface modifications, antibody linking techniques) that will allow maximal targeting of the nanoconstruct to human neuroblastoma in vitro and in vivo. Together with collaborators from other disciplines, we are evaluating theranostic applications such as molecular imaging with MRI, drug delivery and hyperthermia. Our goal is to develop a novel, multipronged approach to treat neuroblastoma and develop a nanotechnological platform to treat other pediatric tumors.
Stem Cell Graft Design
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an established, successful treatment modality for a variety of malignant and nonmalignant conditions such as high-risk leukemias and lymphomas and some otherwise fatal conditions. With current allogeneic transplant regimen, the prolonged period of profound immune deficiency which occurs after transplant until the immune system has functionally recovered leaves the patient at high risk for life-threatening infections. More importantly, it likely prevents the donor-derived immune system from mediating a critical graft-versus-leukemia/tumor effect at a crucial time when minimal residual disease could potentially be eradicated, and the patient cured. Therefore, our lab is working on the pre-clinical as well as translational design of grafts and transplant regimens that lead to fast engraftment, but also provide the patient immediately with potent and activated effector cells such as NK cell or γδ T cells to deliver a strong anti-tumor benefit and protect from potentially deadly infections.
Additional Research Activities
- Clinical Cancer Immunology and Immunotherapy Research
- Hematopoietic Stem Cell Research
- Molecular imaging and cell tracking of tumor cells