Exploring the use of a Virus Based Anticancer Strategy for Lymphoma

A Clinical Trial of VSV-cIFNbeta-NIS Oncolytic Virotherapy for Canine B-Cell Lymphoma

Summary: This study explores the safety and effectiveness of a new virus-based therapy, developed at Mayo Clinic, for dogs with B-cell lymphoma.

Description: Lymphoma is one of the most commonly occurring malignant tumors in dogs. Though treatable, the disease often recurs and spreads. This study will determine the safety, efficacy and prognostic factors of a cancer-killing virus developed by researchers at the Mayo Clinic. Researchers at the University of Tennessee have already determined a safe dosing protocol for this virus in healthy dogs, and this clinical trial will test the dosing in dogs with B-cell lymphoma.

Using state-of-the-art cancer imaging, the study team will determine how successfully the virus spreads to sites of cancer. They will also study the dogs’ immune responses to the virus. This study provides the first robust assessment of a new anticancer strategy that has the potential to significantly improve quality of life and outcomes for dogs suffering from lymphoma.

Co-sponsored with the Morris Animal Foundation, Grant Number: D14CA-002

RESEARCHERS

Dr. Amy K. LeBlanc
University of Tennessee

Developing Ways to Improve Cancer Treatments

Methods of predicting tumor response to a given chemotherapy protocol have historically focused on a few traits that could be measured in biopsy samples. Recent approaches have looked at the activity of genes within tumors to predict a tumor’s sensitivity to a given drug. Because many dogs with osteosarcoma eventually succumb to it in spite of treatment, a method to optimize chemotherapy selection could improve outcomes for dogs with this type of cancer.

Funded by Morris Animal Foundation, researchers from Colorado State University are developing a model to determine whether an osteosarcoma tumor from an individual dog is sensitive to a specific chemotherapy drug. This project is based on the idea that the genetics of human and canine cancers are similar enough that the wealth of data on human cancer genes and drug sensitivity can be mined and applied to canine cancers to aid in chemotherapy selection for dogs.

So far, researchers have collected genetic and drug-sensitivity data from canine cancer cell lines to compare with human data used to evaluate an individual tumor’s likely response to specific chemotherapy drugs. Currently, the researchers are looking at several commonly used drugs—doxorubicin, carboplatin and cisplatin—to determine if the human models will be accurate in predicting canine cancer responses to these drugs. Results are promising, and the next step is to use the gene expression–based models to search drug databases for drugs that could be more effective in treating canine osteosarcoma patients than the drugs that are the current standard of care.

If the study is successful, canine patients could be treated with the drug that would be most effective for their particular cancer. Data from this study could also lead to new treatment options for osteosarcoma. This type of approach, known as precision medicine, allows for tailored therapy that better controls cancer growth and spread and minimizes the possibility of using an ineffective drug that may cause unwanted side effects.

Co-sponsored with the Morris Animal Foundation, Grant Number: D13CA-044

RESEARCHERS

Daniel L. Gustafson, PhD
Colorado State University

Assessing How a Protein Helps Hemangiosarcoma Cells Survive

Canine hemangiosarcoma is a common and highly fatal cancer in dogs. Recent evidence suggests that populations of cancer stem cells give rise to tumors, promote tumor growth and are the main culprits behind drug resistance and disease recurrence.

This study examines how a protein expressed by stem cells contributes to the maintenance and survival of hemangiosarcoma stem cells.

Co-sponsored with the Morris Animal Foundation, Grant Number: D13CA-062

RESEARCHERS

Dr. Erin B. Dickerson, PhD
University of Minnesota

Determining a More Effective Treatment for Canine Lymphoma

This study evaluates the efficacy of two antibodies that could treat canine B-cell lymphoma. The investigators theorize that either antibody alone will kill lymphoma cells and delay tumor progression but that the combined effect of the two antibodies will be more effective as a treatment for dogs with lymphoma.

Co-sponsored with the Morris Animal Foundation, Grant Number: D13CA-033

RESEARCHERS

Jaime F. Modiano, VMD, PhD
University of Minnesota

Evaluating a Novel Drug for Lymphoma

Lymphoma accounts for an estimated 25 percent of all canine cancers. This study investigates a new therapeutic antibody that appears to effectively kill canine lymphoma cells but does not appear to result in serious side effects. Researchers will work to find the best dosage and evaluate the drug’s safety and effectiveness in dogs with B-cell lymphoma.

Co-sponsored with the Morris Animal Foundation, Grant Number: D12CA-033

RESEARCHERS

Barbara Biller, DVM, PhD
Diplomate ACVIM (Oncology)
Colorado State University

Searching for Ways to Control Hemangiosarcoma Cancer Cells in Dogs

Hemangiosarcoma is a highly metastatic and incurable cancer that can affect dogs at any age. It is particularly prevalent in certain breeds such as Golden Retrievers, German Shepherds and Portuguese Water Dogs. Unfortunately, hemangiosarcoma is a disease that is poorly understood and for which there are currently no good treatment options.

One of the main reasons why therapies fail may be due to the existence of cancer stem cells. These cells are responsible for initiating and maintaining the cells within the tumor and they are also highly resistant to most chemotherapy. Researchers at University of Minnesota, funded by Morris Animal Foundation, are examining the role of small molecules that may serve as signals in the regeneration of hemangiosarcoma stem cells. Specifically, investigators are evaluating the potential to control the activity of hemangiosarcoma stem cells by altering these molecular signals in a way that stops stem cell regeneration and enhances sensitivity to chemotherapy.

So far, preliminary data show that one signaling pathway under study has distinct effects on the regeneration of hemangiosarcoma cancer stem cells in the lab. This signaling pathway seems to affect the stem cells’ efficiency in forming a sphere as part of the self-renewal process. If this signal can be altered, it may reduce the stem cells’ ability to renew and maintain the tumor. Further research is needed to confirm the results.

This study is providing valuable insight into the properties of cancer stem cells that could help in the development of tests to predict a patient’s outcome and appropriate therapies to treat canine hemangiosarcoma. Funding for this project is also supporting the training of a promising, new canine cancer researcher.

Co-sponsored with the Morris Animal Foundation, Grant Number: D13CA-400

RESEARCHERS

Jong Hyuk Kim, DVM, PhD
University of Minnesota

Understanding the Role of Specific Cells in Spreading Lymphoma

One of the limitations in identifying therapeutic targets for canine lymphoma has been the lack of reliable systems to study lymphoma cells in the laboratory. This study uses a culture system, developed by the principal investigator, to maintain lymphoma cells in the laboratory and study a protein that helps lymphoma spread. The findings may highlight novel targets for developing therapies to treat B-cell lymphoma in dogs.

Co-sponsored with the Morris Animal Foundation, Grant Number: D12CA-302

RESEARCHERS

Daisuke Ito, DVM, PhD
University of Minnesota

Developing a New Treatment for Canine Lymphoma

To develop a drug similar to Rituximab that works on canine lymphoma patients.

Blood cell lymphomas affect about 30 dogs in every 100,000. Diffuse large B cell lymphoma (DLBCL) is a common type affecting dogs and is similar to non-Hodgkin’s lymphoma in humans. Current treatment induces remission in about 75 percent of patients but the majority relapse and the lymphoma is drug resistant within six to nine months of diagnosis.

In human medicine a drug called Rituximab is used to treat various types of lymphoma. The researchers in this study will work to develop a drug similar to Rituximab that works on canine lymphoma patients.

The results of this work could lead to the development of the first targeted treatment of canine B cell lymphoma and may significantly improve the outcome for dogs with B cell lymphomas.

Co-sponsored with the Morris Animal Foundation, Grant Number: D12CA-026

RESEARCHERS

Nicola Mason, BVetMed, PhD, DACVIM
University of Pennsylvania

Potential Drug Therapy for Lymphoma

Lymphoma is one of the most common and fatal cancers in dogs. Most dogs treated with chemotherapy go into remission, but the cancer quickly develops drug resistance and recurs. Chemotherapy generally works by initiating apoptosis, a normal process in which cells undergo programmed death. Apoptosis occurs throughout life and is critical for developing and maintaining healthy tissues, but cancer cells develop ways to avoid apoptosis, which allows them to grow and survive in an uncontrolled fashion. Researchers studied a novel compound, PAC-1, that has been shown to induce apoptosis in tumor cells without the presence of chemotherapy. This study attempted to evaluate the safety, dosing and efficacy of PAC-1 in dogs with lymphoma. The researchers felt that this compound held great promise for the treatment of lymphoma and other cancers.

Results

Dogs enrolled in this clinical trial had not responded to other therapies or had owners who could not afford other therapies. PAC-1 works via a different mechanism than traditional chemotherapy and based on preliminary data, it showed promise as a revolutionary treatment for dogs with cancer. Recent study developments, however, indicate that the drug cannot be used safely at the levels needed to produce an anticancer effect. Because of these developments, this clinical trial was discontinued. It is important to note that preliminary data in laboratory cell-line models were promising and that the drug was well tolerated in the initial three dogs that were treated. However, as the study progressed, there was unexpected neurotoxicity. The researchers quickly determined that PAC-1 is not safe for dogs at blood concentrations needed to be therapeutic and therefore terminated the study.

Although the results were not what we hoped for, this study has provided critical knowledge about PAC-1. First, researchers clearly determined that PAC-1 isn’t safe for dogs. It can cause severe and unpredicted neurotoxicity and, therefore, shouldn’t be pursued as a treatment for canine lymphoma. Second, similar drugs are in development, and these findings indicate the need for safer formulations of these drugs for future studies.

NOTE: The entire amount of our co-sponsorship was transferred to another research study and therefore was not lost or wasted by the early termination of this research project.

Co-sponsored with the Morris Animal Foundation, Grant Number: D09CA-082

RESEARCHERS

Dr. Laura D. Garrett,
DVM, Dipl. ACVIM (Oncology)
University of Illinois