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Enhancing Pediatric Sarcoma Immunotherapy by Drug Induced Expression of Tumor-Specific Cryptic Neoantigens

Institution: 
University of Minnesota
Researcher(s): 
David Largaespada, PhD
Grant Type: 
Innovation Grants
Year Awarded: 
2016
Type of Childhood Cancer: 
Osteosarcoma, Rhabdomyosarcoma
Project Description: 

Background

Current treatment for pediatric sarcoma (traditional chemotherapy, surgery and radiation) is usually not effective when metastasis has occurred. Moreover, the traditional therapies have lifelong negative health effects on survivors including loss of limbs, heart disease, metabolic syndrome and more. For both of these reasons, therapies that are effective when the traditional ones fail and that leave the patient more intact from a health standpoint are highly desirable. Immunotherapy offers an alternative treatment to improve survival of pediatric sarcoma patients and also has the potential to reduce current treatment-related complications.

Project Goal

This project aims to make it possible for the immune system, with its exquisite specificity, to recognize a patient's sarcoma tumor cells as foreign invaders and then destroy all of them. This has been tried in the past, but not using the approach we have devised. We have developed an approach in which it is possible to use drugs, specifically to force tumor cells to express foreign proteins on their surfaces in such a way as to alert the immune system. These drugs we propose could very realistically and safely be applied in pediatric sarcoma patients. After we give the patient a vaccine made of these foreign proteins, these tumor cells will be rejected by the patient's own immune system or patient's own white blood cells trained to recognize these foreign proteins on tumor cells. Our project could provide immunotherapy vaccine treatments that would benefit and allow more pediatric sarcoma patients to achieve true cures.

"Funding from Alex's Lemonade Stand Foundation will help us reach our research goal to make immunotherapy treatment benefit more pediatric sarcoma patients allowing more pediatric patients to achieve true cures.  Our research project aims to make it possible for the immune system, with its exquisite specificity, to recognize a patient's sarcoma tumor cells as foreign invaders and then destroying all of them.  We have developed an approach in which it is possible to use drugs, specifically to force tumor cells start to express foreign proteins on their surfaces in such a way as to alert the immune system.  Then these tumor cells will be rejected by the patient's own immune system after we give the patient a vaccine made of these foreign proteins or patient's own white blood cells trained to recognize these foreign proteins on tumor cells.  We will achieve our research goal by making pediatric sarcoma vaccination a reality." Dr. Largaespada