Paul M. Sondel, PhD, MD

Departments: Pediatrics, Human Oncology, Genetics                                         

Immunology Focus area: Cancer Immunology and Immunotherapy           

Descriptive Title of Research:  Enhancing Antibody-directed Innate Immunity to Improve Cancer Outcome             

Research Description: Since joining the lab of Fritz Bach in Dec. 1969 as a 2^nd year undergrad, my training and career have been focused on using the immune system as cancer treatment. In 1980 I became faculty at UW-Madison and have led a research team that has pursued: a) basic cancer immunology; b) early clinical immunotherapy trials; and c) the translational-preclinical research needed to connect basic science to clinical testing. This work has been supported through many sources, including continuous NCI support, with me as PI/PD since 1982 (including R01, R35 and multi-investigator grants). From 1990-2016, I was the head of our UW Division of Pediatric Hematology, Oncology and Bone Marrow Transplantation, and am now Research Director. I have served nationally on many cancer immunology advisory committees and have a steady record of service to the NCI, through study sections, advisory boards, and review panels. I have previously held other administrative leadership positions at UW [i.e.: Vice Chair of Pediatrics; Asso. Director of the UWCCC; and leader of the UWCCC Immunology-Immunotherapy Program]. Over the past few years we have seen real clinical benefit from the approaches my research team is pursuing. I am convinced that far greater application of immunotherapy principles can be integrated into (or replace components of) the “standard” for most forms of cancer. The goal is more effective therapy with less long and short- term toxicity.  Furthermore, I believe that the widespread application of effective immunotherapy to worldwide cancer treatment will be best served by strategies that utilize “off the shelf” agents. I am focusing my efforts on these important research and translational goals.

We have identified a novel combination therapy (“In Situ Vaccination”) given directly to a large existing tumor that enables it to function as a potent vaccine, providing long-lasting cure of mice from large tumors that were previously non-curable with other immunotherapy approaches. Following local radiotherapy (RT), we directly inject a tumor-reactive immunocytokine [a tumor-reactive monoclonal antibody (mAb) linked to IL2, a potent immune cell activator]. Most mice bearing a single large melanoma show tumor elimination with long lasting protective immunity with this approach (Morris et al, Cancer Research, 76:3929, 2016.In mice with 2 tumors, delivering RT to both the 1^st + 2^nd  tumors, or adding checkpoint-blockade therapy using an anti-CTLA-4 mAb, enables injection of immunocytokine to the 1^st tumor to eradicate it as well as the second tumor in most mice. Clinical testing in melanoma is being initiated, and preliminary results are similar in mice bearing pancreatic cancer. We hypothesize that In Situ Vaccination will also be effective in other tumors that appear resistant to checkpoint-blockade. Our ongoing preclinical work is evaluating the potency of in situ vaccination in distinct mouse models, characterizing the immune suppression from multiple tumors, determining how best to achieve meaningful-lasting tumor eradication, and identifying the mechanisms underlying these important clinically translatable findings. Our goal is to transform these approaches into evidence-based clinical testing.

Link to Publications:

List of ~300 manuscripts in PubMed: http://www.ncbi.nlm.nih.gov/pubmed/?term=Sondel+P

Listings (82) in Pub Med Central:  http://www.ncbi.nlm.nih.gov/pmc/?term=sondel+p

379 manuscripts in myNCBI: http://bit.ly/2f7bXmY

Graduate Program Affiliations:  Cell and Molecular Biology, Cell and Molecular Pathology, Genetics, Immunology, Biotechnology, Clinical Research

Lab Website:   https://www.pediatrics.wisc.edu/research/research-groups/sondel/