Research

Fall 2019 Lab Update

The main goal of our work this year has been to engineer bacteria that colonize tumors consistently, comprehensively and without toxicity. These bacteria have been modified to secrete molecules into the tumor that stimulate the immune system to destroy the cancer and guard against its return.

This year we have:

  • Completed engineering of bacteria that allow delivery of anticancer molecules to tumors throughout the body without therapy-limiting toxicity. We are now working to determine optimal dosing of these bacteria to eliminate tumors.
  • Obtained a library of DNA to be screened for human-specific molecules to replace the mouse-specific molecules currently secreted into tumors by our bacteria, which will be necessary before proceeding to clinical trials. This library also allows us to screen for additional cancer-killing molecules.
  • Worked with additional strains of bacteria to accomplish oral delivery of the therapy in addition to the current intravenous delivery method.
  • Expanded our mouse colony so that we now have mice with tumors that can be used for weekly experiments.

We are grateful for your support and excited about the anticancer immune therapy being developed with that support.

November 2018 Lab Update

Significant positive advances are as follows:

1. We are using a mouse colony that mimics human cancer, called the autochthonous approach, where the cancer starts from a single cell and develops just as human cancer progresses. This system is much more efficient than what drug companies use, where the cancer is injected under the skin. Our system allows a natural progression of stimulating the immune system in proper, realistic fashion.

2. We have instituted antibodies against checkpoint inhibitors PDL-1 and CTLA-4. The 2018 Nobel Prize for Medicine was awarded this year to the two groups (Japan and Texas) for the discovery of these immune modulators. The biggest drawback to the use of the checkpoint immune inhibitors is the toxic side effects. We have been able to use our innovative Salmonella Delivery System to deliver both the PDL-1 and CTLA-4 proteins without any toxicity whatsoever.

3. We are working at present to develop a method to alter the blood supply to the solid tumor. By changing how blood flows to a tumor, we can cause necrosis, or disintegration of the tumor. This changes the tumor microenvironment to make it more attractive of our Salmonella to invade and colonize these solid cancers. Thus, we are able to use Salmonella to act as an in situ factory to produce a cocktail of immune modulating proteins directly within the tumor itself and eliminate any toxic side effects.

4. Also, we have added promoter genes to our genetic systems that also enhance the effect of all the killing power of the tumor with our genetic engineering. Hopefully, with your continued support and our recent progress, we expect to not only kill the tumor, but also with the application of our system, prevent later metastatic spread.

5. In addition to the genetic engineering advance above, we also added an experiment with chemotherapy from 0-100% to helpbreak down part of the tumor. We are very excited to report that a 75% reduction in the dose of chemotherapy coupled with our genetic engineering construct kills as much tumor as 100% chemotherapy. This advance also gives quality of life to patients without the grave side effects of 100% chemotherapy itself.

Thank you for your generosity that allows us to continue this most exciting work. Our lab was chosen to help run a consensus conference generated by the National Cancer Institute and the National Institute of Health last year. This gave great exposure to our lab and system as we presented our approach and helped lead the seminar. This is a complicated approach but we are making significant progress and again, thank you for your help.

2019 Lab Personnel:

The principle investigator of our cancer therapy development, Dr. Daniel A. Saltzman, has studied the use of attenuated Salmonella as a tumor-targeted vehicle to carry immune modulating proteins to solid tumors for over 20 years. His Ph.D. thesis was in this field. He wrote and published one of the very first manuscripts highlighting the use of Salmonella as a potential cancer treatment and has been sought out as an expert in this field throughout the world. Despite his clinical duties as an active pediatric surgeon, basic science research with a focus on translating that research to the clinic has always been his passion. His dedication to the field of microbial based cancer therapy was recently recognized when he was invited to co-chair a session in a recent NCI sponsored consensus conference on microbial based cancer therapy. Dr. Saltzman’s expertise, experience, training, leadership, and tenacity to successfully carry out the proposed research inspires our team.

As a co-investigator, Dr. Janet L. Schottel provides a wealth of knowledge in microbiology, biochemistry and molecular biology, and extensive experience in bacterial physiology. During her career as a professor she has mentored numerous graduate and undergraduate students on projects concerning transcriptional and translational regulation of gene expression, mechanisms of mRNA degradation, secondary metabolite production, plant-pathogen interactions, biological control of disease, biosensor development, and mechanisms of desiccation tolerance. In addition to providing insight into the design of experiments and analysis of data, Dr. Schottel supervises staff and students involved in the development of our cancer therapy in her laboratory in the Department of Biochemistry, Molecular Biology & Biophysics at the University of Minnesota.

Our laboratory director, Dr. Lance B. Augustin, began his career in life science research over thirty years ago as a graduate student in the University of Minnesota Medical School Department of Biochemistry. During the ensuing years he developed skills in microbial engineering and molecular biology. He has expertise in engineering mammalian cells and extensive experience with mouse husbandry and surgery. During his work as a member of cancer research teams he has accumulated the knowledge of cancer biology and immunology needed for his current position directing the efforts of a laboratory developing bacterially delivered anticancer immunotherapy. Dr. Augustin has authored several publications contributing new knowledge to our understanding of cancer.

Additional full-time staff in our laboratory include Dr. Liming Milbauer with over 20 years of experience in: biochemical assays, nucleic acid manipulation, bacterial strain construction, tissue culture, and flow cytometry. Dr. Milbauer is responsible for data collection and analysis and she provides daily oversight of all animal experiments.

Ms. Sara Hastings carries out daily experimentation and manages our mouse breeding colony. Ms. Hastings joined our team in 2017 after completing her B.S. degree at Carleton College.

The Basics:
The lab is researching how to use salmonella to transport cancer-fighting therapy to tumors. Unlike current practices to kill cancer, this method causes no side effects.

How it Works:
Salmonella has a natural attraction to cancer cells.

The bacteria can be genetically modified so that it doesn’t cause food poisoning, which is what we typically associate salmonella with.

By adding the cancer-fighting therapy to salmonella, the bacteria goes directly to the tumor sites and disable its ability to survive.

Delivering cancer-fighting therapy only to the tumor allows the healthy cells surrounding the tumor to not be affected. This means no side effects, safer delivery, and – most importantly – patients are able to tolerate treatment much easier than traditional methods.

The Statistics:

We have demonstrated in the laboratory:

1/4th dose of the chemotherapy added to our genetic engineering construct has as much killing power as 100% of chemotherapy.

90% reduction in tumor size and weight in a primary tumor model (Neuroblastoma).

60-90% reduction in tumor size, weight, and number in a Metastic tumor model.

Your Contribution:
When you donate to the Arnold S. Leonard Cancer Research Fund, you are helping find a cure. Donate today to help make a difference!