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Immune platforms to monitor GD3 based osteosarcoma vaccine given concurrently with a carboplatin chemotherapy protocol and surgery

Immune platforms to monitor GD3 based osteosarcoma vaccine given concurrently with a carboplatin chemotherapy protocol and surgery

Immune platforms to monitor GD3 based osteosarcoma vaccine given concurrently with a carboplatin chemotherapy protocol and surgery

Veterinary Cancer Society
Veterinary Cancer Society
on behalf of Missouri Veterinary Medical Association


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Launch date: 22 Dec 2016
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Last updated: 10 Feb 2017

Reference: 167573

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Because of the limits of conventional therapy especially in high-grade sarcomas and melanoma, we have explored tumor immunology using GD3 (tumor antigen) based cancer vaccines in canine melanoma and osteosarcoma. The disialyl gangliosides GD2/GD3 have been implicated in the enhancement of malignancy in a number of human and animal cancers and as a tumor antigen target for immunotherapy. In a recent abstract presented at an AACR Conference we reported on the co-expression of GD2/GD3 in four canine OSA cell lines. Results confirmed the expression of GD2/GD3 in the canine cell lines and their possible role in migration and metastasis. In a prospective trial we are vaccinating dogs with naturally occurring OSA receiving standard of care (surgery [amputation] & carboplatin) to improve survival and to investigate the expression profiles of GD2/GD3 and immune response from tumor aspirates and blood samples overtime. A parallel study will investigate the checkpoints of immunity that may influence the immune response to osteosarcoma. Forty dogs will be entered into the study with confirmed OSA, 20 will receive the vaccine plus standard of care and 20 dogs will receive only the standard of care (amputation and intent to treat with 6 doses of carboplatin). The dogs are being vaccinated according to a predetermined protocol during chemotherapy and staged. The median survival, immune response and GD2/GD3 expression profile of the vaccine group will be compared to dogs receiving standard of care alone. The Milner comparative laboratory has developed flow cytometric platforms to monitor changes in immune cells (CD5, CD21, CD4, CD8, CD14, CD11b, MHCII, Foxp3, and CD1d Tetramer). In addition flow cytometry platforms and IHC arrays have also been developed for checkpoints of immunity PD1, PDL-1 etc. Currently eight dogs have enrolled into the study and have received standard of care and vaccination. Preliminary expression profiles of immune cells compared to normal dogs show changes consistent with carboplatin myelosuppression and changes in immune response. High expression of Foxp3+/Cd4+ cells were found in dogs on presentation to the trial and on receiving chemotherapy, a significant decrease in Foxp3+/Cd4+ cells occurred with subsequent increases in T-reg cells with metastases. Complete necropsy post therapy in three dogs showed changes in metastatic profiles; 2/3 showed no metastatic disease to the lungs, but metastases occurred to bone and kidneys. Early results seem to show a possible change in metastatic profile for osteosarcoma although data is immature at this time.
Acknowledgement: The study is funded by a grant from the American Kennel Club Animal Health Foundation and the UF Foundation.


Learning Objectives:
• To identify the problems and advantages associated with the timing of immunotherapy and chemotherapy in patients where chemotherapy remains the standard of care.
• To understand the technology used to monitor immune cells that could contribute to immune response or inhibition of the immunotherapy (Immune checkpoints).
• To understand the changes in immune cells overtime with chemotherapy and immune modulation with cancer vaccine.
Veterinary Cancer Society

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Veterinary Cancer Society
on behalf of Missouri Veterinary Medical Association

Dr. Rowan Milner - Dr Milner graduated from the University of Pretoria (UP), South Africa in 1980. He spent 10 years in GP practice and returned to UP in 1993 to specialize in small animal medicine. In 1998, he received diplomat status in the European college of Veterinary Internal Medicine. He began a PhD in the College Medicine UP using novel radiopharmaceuticals, which led to further research in canine osteosarcoma as a model for human disease. He joined the University of Florida’s Internal Medicine Service in October 2001 subsequently in 2005 together with Dr David Lurie began the UF Oncology service. Dr Milner is boarded in the American & European College of Veterinary Internal Medicine (Oncology). He is currently Professor and Chair of the Department of Small Animal Clinical Services CVM and Director of the Comparative Oncology Laboratory and has an affiliate appointment in the UF College of Medicine Pediatric Oncology. Has main research goals have been to develop research in true disease models of human cancer i.e. naturally occurring translational models. He is currently the principal investigator of the UF melanoma trial and the AKC CHF funded osteosarcoma vaccine trial.

Current Accreditations

This course has been certified by or provided by the following Certified Organization/s:

  • Missouri Veterinary Medical Association
  • 1.00 Hours -
    Exam Attempts: 3
    Exam Pass Rate: 60

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