Awarded DRP Pilots

2023: Baschnagel | Galmozzi | Hu | McCarthy | Ward

2022: Hernandez | Kimple | Renewal: Gumperz

2021: Gumperz | Weaver | Renewal: Hong | Tang

2020: Bradfield | Hong | Tang | Weichert | Renewal: Welham | Kennedy/Bruce

2019: Galipeau | Kimple | McMillan/Yadav | Thibeault | Welham | Wheeler

2018: Lewis | Hong | Renewal: Beebe | Tibbetts | Weaver

2017: Beebe | Kennedy/Bruce | Tibbetts | Weaver

2023 Awards

Andrew Baschnagel, MD

Associate Professor
Department of Human Oncology

Preclinical evaluation of a novel theranostic MET binding nanobody in MET-expressing head and neck cancer

Abstract

Our project aims to develop novel therapeutic approaches for patients with head and neck cancer by evaluating a highly selective MET-binding camelid antibody for imaging and targeted radionuclide therapy. Our team will evaluate the biologic performance of the antibody, assess its utility as an imaging agent, and assess its potential as a therapeutic agent using novel patient-derived preclinical models. We will also evaluate its binding to patient tumor samples. At the completion of this project, we hope to provide robust evidence for the further development of MET-targeted theranostics for use in patients with head and neck cancer.

Andrea Galmozzi, PhD

Assistant Professor
Department of Medicine – Endocrinology

Elucidating the role of polyamines in HNC-induced cachexia

Abstract

Cancer Cachexia (CC) is a condition where individuals with cancer experience weight loss, particularly in muscle and fat tissue, and it is a leading cause of over 20% of cancer-related deaths. The prevalence of cachexia varies depending on the type of cancer, with up to 60% of patients with Head & Neck cancer (HNC) developing this condition. The current therapies used to treat CC are limited and mainly focused on nutritional supplementation. However, recent studies suggest that cachexia is not only due to malnutrition but also a result of a tumor-induced metabolic change in the body. CC progression starts with the loss of fat tissue, followed by muscle wasting, and is characterized by increased adipose tissue inflammation, insulin resistance, and adipocyte lipolysis.

In our studies, we found that cancer cells derived from highly cachectic tumors, including HNC, have elevated levels of polyamines and that these molecules can promote lipid mobilization from fat cells. In this project, we plan to characterize the effects of Head & Neck cancer cells on adipocyte function and evaluate the contribution of polyamines to cancer-induced adipocyte dysfunction and adipose tissue waste in preclinical models of Head & Neck cancer.

This work will provide a better understanding of the role of polyamines in body weight loss in HNC-induced cachexia models and set the foundation for developing more effective strategies to restore adipose tissue function in cancer patients with cachexia.

Rong Hu, MD, PhD

Associate Professor (CHS)
Department of Pathology and Laboratory Medicine

Oral Squamous Cell Carcinoma in Non-Smokers Non-Drinkers

Abstract

The incidence of oral cancer in patients who do not have any of the established risk factors (such as smoking, drinking, high-risk HPV infection) is increasing. We hypothesize there may be other risk factors involved in the development of this cancer type in non-smoker and non-drinker populations. In this study, we propose to investigate if there are other infectious agents beyond high-risk HPV that could be associated with the development of these cancers.

Danielle McCarthy, PhD

Associate Professor
Department of Medicine; Center for Tobacco Research and Intervention

Smoking cessation treatment engagement and effectiveness in head and neck cancer patients: A feasibility pilot

Abstract

Continuing to smoke after developing head and neck cancer is associated with negative outcomes. Although many people living with head and neck cancer want and try to quit smoking, relatively few receive support or smoking treatment. In addition, little is known about the best ways to help such patients quit smoking. Cancer care teams could help connect more of their patients who smoke with treatments to help them quit. The proposed project will test new ways for the University of Wisconsin Carbone Cancer Center to connect patients receiving treatment for head and neck cancer with evidence-based smoking treatments delivered remotely and at no cost to patients. The goal of the project is to identify ways to help more patients use and benefit from smoking treatment, and to reduce disparities in treatment access among historically undertreated patient groups. Eligible patients will be offered readily available and free tobacco use treatments, or to join a clinical trial. The clinical trial will compare 2 active treatments (with no placebo) to see which treatment is most effective and efficient in helping patients with head and neck cancer quit smoking. Data collected from the EHR will be analyzed, along with input from stakeholders, to assess and improve referral and treatment processes. Thus, this project will pilot test both health system changes designed to enhance the entry of patients into smoking treatment and produce evidence on how well different smoking treatments work.

Earlise Ward, PhD, MS

Professor
Department of Family Medicine and Community Health

IONA Mind Mobile Mental Health Treatment App for HNC Patients and Survivors with Depression and/or Anxiety

Abstract

Head and neck cancers (HNC) represent the 7th most common cancer worldwide. HNC usually requires multimodality treatments, and affect critical functions such as breathing, speaking, swallowing, and eating. Besides functional impairments, HNC survivors experience altered appearance due to the preparation to undergo cancer treatments (teeth extraction) and due to cancer therapies. All the changes imposed by HNC and oncological treatments, and the need to adapt to the “new normal,” often cause distress, anxiety and depression. Some researchers report HNC is the most psychologically distressing and traumatic of all cancers. The prevalence of depression among HNC survivors is as high as 48.3% after treatment. Guidelines for HNC care recommend distress screening followed by psychological support when clinically needed. Low intensity Cognitive Behavioral Therapy (LiCBT), an evidenced based depression treatment has potential to effectively treat depression and anxiety in HNC patients and survivors. Colleagues in the UK have developed the IONA Mind mobile phone app based on LiCBT. It is a self-help treatment of depression and anxiety that is delivered on a telephone app. We propose adaptation of the IONA Mind app and pilot testing the app with 30 HNC patients and survivors examining feasibility, preliminary efficacy, satisfaction and acceptability. Results of this pilot study will inform a future RCT examining efficacy of the IONA Mind app in a larger sample

2022 Awards

Reinier Hernandez, PhD

Assistant Professor
Department of Medical Physics

In situ vaccination combining IL-2 engineered extracellular vesicles and radiation therapy

Abstract

Due to the lack of effective therapies for head and neck cancer patients unresponsive to immunotherapies, novel treatment approaches must be investigated. We propose using extracellular vesicles (EVs) to carry an immune-activating treatment, interleukin-2 (IL-2), with increased potency and decreased toxicity. Using an innovative approach, we will test whether our IL-2 enriched EVs enhance immune responses when combined with radiation therapy to destroy cancerous cells. Our goal is to expand the arsenal available for cancer immunotherapy, offering non-toxic, curative opportunities for patients with cancer of any status and type.

Randy Kimple, MD, PhD

Associate Professor
Department of Human Oncology

Cetuximab augmented immune effector cell therapy using head and neck cancer patient samples

Abstract

This project seeks to develop a new approach to treat patients with head and neck cancer. This process involves first removing immune cells from the blood of a patient. These cells are then processed to remove cells we don’t want. The remaining cells are stimulated and then injected back into the patient. At the same time, the patient is given a drug, cetuximab, that is already used for head and neck cancer patients. In the first part of this grant, we want to ensure that head and neck cancer patient’s blood cells can be used in this way by collecting blood from five volunteers. We will prove that we can isolate the target cells from these patients and use these isolated cells to treat head and neck cancer cells. In the second part of the grant, we will evaluate the ability of this treatment to decrease tumor burden in a mouse model of metastatic head and neck cancer. Together, this work will provide key data to support future grant applications and a novel clinical trial testing this combination in head and neck cancer patients.

2021 Awards

Jenny Gumperz, PhD

Professor
Department of Medical Microbiology and Immunology

Activation of HNC patient T cells using a novel iNKT-DC conjugate cellular immunotherapy

Abstract

Suppression of antigen-specific T lymphocytes is now recognized as a key factor in cancer. Current immunotherapies focus on either interrupting suppressive pathways (checkpoint inhibition), or on delivering genetically-modified cytolytic effector cells (chimeric antigen receptor or CAR-T cells) to directly kill the cancer cells. The Gumperz lab has discovered an alternative strategy to activate human antigen-specific T cell responses that utilizes stable conjugates (adhered pairs) composed of invariant natural killer T cells (iNKT cells) and monocyte-derived dendritic cells (DCs). The iNKT-DC conjugates have elevated cell surface expression levels of multiple co-stimulatory ligands that are known to potently activate T lymphocytes. In preliminary studies we used a humanized mouse model to show that this therapy promotes T cell-mediated regression of human EBV-driven lymphomas in vivo. Here, we will test whether iNKT-DC conjugates promote the activation of T cells from human papilloma virus (HPV)-positive and -negative HNC cancer patients in vitro, and will use recombinant HPV antigens to investigate their ability to activate antigen-dependent T cells. These studies will provide a critical proof of principle to establish the potential of this novel cellular immunotherapy approach for treating HNC patients.

Award Renewed in 2022

Beth Weaver, PhD

Professor
Department of Cell and Regenerative Biology

A novel mechanism of radiosensitization by docetaxel in HNC

Abstract

In the United States, approximately 56,000 cases of head and neck cancer are diagnosed every year, many of which are caused by infection with human papillomavirus (HPV). Both HPV-positive and HPV-negative head and neck cancers are typically treated with radiation with or without chemotherapy. Unfortunately, 8-year overall survival is only 71% for HPV-positive and 30% for HPV-negative head and neck cancer patients. Thus, new treatment strategies are necessary. However, treatment can lead to difficulty with speech and swallowing, permanent dry mouth, neck stiffness and pain. Thus, a biomarker to distinguish patients that will respond to lower levels of treatment from those that need more aggressive therapy would provide a substantial benefit. Our evidence suggests that a characteristic of head and neck cancers known as chromosomal instability (CIN) can predict response to radiation. Additionally, our data support the idea that patients with tumors unlikely to completely respond to radiation will benefit from additional treatment with the FDA approved drug docetaxel. Here we will test our ideas about how docetaxel works in head and neck cancer and whether docetaxel does indeed sensitize head and neck cancer cells to radiation through a completely novel mechanism, which could allow us to determine which patients will benefit from this drug. Successful development of a method to identify and sensitize resistant head and neck cancers would substantially improve patient outcomes.

2020 Awards

Christopher Bradfield, PhD

Professor
Department of Oncology

Development of mouse models to study aryl hydrocarbon receptor signaling in head and neck cancer

Abstract

Animal models have played an important role in our understanding of head and neck cancer (HNC) biology. Recent advances in genome editing technologies has allowed us to create more innovative models to study cancer development and progression as well as evaluate potential therapies. The aryl hydrocarbon receptor (AHR) pathway may play a role in HNC. The AHR is a transcription factor that binds a range of compounds, including environmental chemicals. However, recent studies have suggested that AHR has other roles in biology, and altering AHR signaling may be a viable route for HNC therapeutics. We will develop new animal models that can be used to study AHR signaling in HNC. We will first build on the existing lox-stop-lox (LSL)-KrasG12D mouse model by linking a fluorescent marker, tdTomato. This model has a mutation that can be expressed and spontaneously develop tumors. In our model, we will add a fluorescent marker so that we can visually identify cells that have the mutation. We will also create a Cyp1a1-Cre mouse model which expresses Cre recombinase in all cells that express Cyp1a1, a well-established and inducible target of AHR. We will also evaluate which tissues and cell populations Cre recombinase is expressed after AHR induction. We will also evaluate our ability to control how many cells respond to AHR induction. Creation and characterization of these models is a crucial first step in our ability to study the AHR pathway in HNC.

Seungpyo Hong, PhD

Professor
Pharmaceutical Sciences

Bispecific Nanocarriers for Synergistic Effect of Immunochemotherapy

Abstract

Head and neck cancer is the sixth most common cancer. It is estimated that >50,000 Americans will be diagnosed with this disease this year. Although a few treatment options are currently available, it is still very difficult to effectively treat metastatic head and neck cancer. An emerging treatment option is to utilize patients’ own immune systems, known as immunotherapy, which can be synergistically effective when used together with conventional chemodrugs. Furthermore, considering the side effect from therapies that are not specific to cancer cells, a drug delivery system that integrates cancer targeting, immunotherapy, and chemotherapy would be a promising approach to substantially increase the treatment efficacy. We therefore aim to develop a new delivery system that carries both immuno- and chemo-drugs specifically to cancer cells only, to maximize the therapeutic efficacy while minimizing toxic effects. To realize this goal, we will engineer a nanoparticle system that contains targeting agents (peptides that are selective to tumor cells) and drug cargo (agents that boost up the immune system against tumor and a commonly used chemodrug). We will then test this nano-scale system using cancer cells and tumor-bearing mice. Upon completion of this study, we will have engineered a novel nanocarrier that is biologically validated, which will help us to successfully compete for larger federal grants to ultimately translate this technology to help head and neck cancer patients.

Award Renewed in 2021

Weiping Tang, PhD

Professor
Pharmaceutical Sciences

Development of small molecules that can selectively promote the degradation of STAT3 for the treatment of Head and Neck Cancer

Abstract

We propose to develop novel small molecule drug candidates that can engage the body’s own natural protein disposal system to remove a protein called STAT3, which promotes the growth of head and neck cancer (HNC). Many small molecule ligands have been developed for STAT3. Although these ligands can bind to STAT3, most of them only showed moderate inhibitory activity for the function of STAT3 in cells and preclinical models. Our lab recently developed a platform that can quickly generate small molecule degraders for various oncogenic proteins. These small molecules could selectively bind to the specific oncogenic protein target and promote its degradation in cell’s natural protein disposal system. These small molecule degraders showed potent anticancer activity for various cancer cell lines. We propose to apply this platform to the development of drug candidates that can remove the STAT3 protein for the treatment of HNC. We anticipate that novel STAT3 degraders with potent anticancer activity for HNC will be generated from the pilot study in year-1. We will further optimize the pharmacological properties of these molecules in year-2. These data will be used as the preliminary results for the application of major external grants to advance the preclinical development. If the preclinical data are promising, a clinical trial will be initiated with appropriate partners for the development of novel therapeutics to treat HNC patients.

Award Renewed in 2021

Jamey Weichert, PhD

Professor
Department of Radiology

Theranostic Use of Gadolinium Based Alkylphosphocholine to Overcome Radioresistance In Head and Neck Cancer

Abstract

Most patients with head and neck cancer (HNC) receive radiation therapy (RT). Although RT is very effective at causing damage to tumor cells by depositing energy (dose), it also can hurt healthy tissue around the tumor. Avoiding normal tissues is even important for HNC patients whose cancer comes back following RT because many of these patients are curable with additional treatment approaches; however, re-treatment is challenging without causing normal tissue damage. The emphasis in radiation oncology to better shape the dose to only the tumor has led to advances in image-guided RT. A way to “light up” the tumor so that it can be “seen” would make RT safer by helping to avoid normal tissue. Following intravenous injection, our tumor-targeting carrier molecule, NM600, can selectively deliver a variety of payloads to tumors in vivo. For example, Gd-NM600 has been shown by MRI to brighten a wide variety of tumors, including HNC, for up to 7 days. Gd-NM600 not only makes tumor margins more visible it also can be used to do real-time tumor tracking with MR IGRT systems, like the ViewRay. In addition, Gd-NM600 may provide a dose boost which may lead to better clinical results. The primary goal of this proposal will be to test whether Gd-NM600 can “light up” HNC using MRI. A secondary goal of this proposal will be to test if the dose boost from Gd-NM600 improves HNC survival. Future work will entail testing in larger animals on the clinical ViewRay system.

2019 Awards

Jacques Galipeau, PhD

Professor
Department of Medicine

Intra-salivary gland autotransplantation of marrow mesenchymal stromal cells for treatment of radiation induced xerostomia – FDA IND enabling studies

Abstract

Dry mouth is a significant toxicity for the 80% of head and neck cancer patients treated with radiation therapy. To address the lack of effective therapies for this problem, in this grant we will establish the preliminary data needed to apply for FDA approval to test a cellular therapy (injection of specialized cells called mesenchymal stromal cells or MSCs) to treat radiation-induced xerostomia. We will demonstrate that MSCs from patients treated for head and neck cancer have the ability to expand and produce the factors that are important to improve salivary function, that we can quantitative and qualitative measures of salivary production that will be tracked in a clinical trial, and that by using a mouse model of radiation-induced salivary dysfunction we can identify the specific factors made by MSCs that are critical for improving salivary gland function.