A phase I clinical study to evaluate safety of orally administered, genetically engineered Salmonella enterica serovar Typhimurium for canine osteosarcoma

Sara E. Fritz; Michael S. Henson; Emily Greengard; Amber L. Winter; Kathleen M. Stuebner; Una Yoon; Vicki L. Wilk; Antonella Borgatti; Lance B. Augustin; Jaime F. Modiano; Daniel A. Saltzman

doi:10.1002/vms3.32

A phase I clinical study to evaluate safety of orally administered, genetically engineered Salmonella enterica serovar Typhimurium for canine osteosarcoma

Sara E. Fritz, Michael S. Henson, Emily Greengard, Amber L. Winter, Kathleen M. Stuebner, Una Yoon, Vicki L. Wilk, Antonella Borgatti, Lance B. Augustin, Jaime F. Modiano, Daniel A. Saltzman

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Abstract

We conducted a prospective phase I study to evaluate safety of an orally administered Salmonella encoding IL-2 (SalpIL2) in combination with amputation and adjuvant doxorubicin for canine appendicular osteosarcoma. Efficacy was assessed as a secondary measure. The first dose of SalpIL2 was administered to 19 dogs on Day 0; amputation was done after 10 days with chemotherapy following 2 weeks later. SalpIL2 was administered concurrent with chemotherapy, for a total of five doses of doxorubicin and six doses of SalpIL2. There were six reportable events prior to chemotherapy, but none appeared due to SalpIL2. Dogs receiving SalpIL2 had significantly longer disease-free interval (DFI) than a comparison group of dogs treated with doxorubicin alone. Dogs treated using lower doses of SalpIL2 also had longer DFI than dogs treated using the highest SalpIL2 dose. The data indicate that SalpIL2 is safe and well tolerated, which supports additional testing to establish the potential for SalpIL2 as a novel form of adjuvant therapy for dogs with osteosarcoma.

Original language	English (US)
Pages (from-to)	179-190
Number of pages	12
Journal	Veterinary Medicine and Science
Volume	2
Issue number	3
DOIs	https://doi.org/10.1002/vms3.32
State	Published - Aug 2016

Bibliographical note

Funding Information:
The authors thank the nursing and technical staff of the Oncology and Surgery Services of the VMC, University of Minnesota for assistance with clinical management of the dogs in this study, Dr. Roy Katz at CustomRx Compounding Pharmacy for assistance compounding SalpIL2, and Drs. Brenda Weigel and Denis Clohisy for assistance with study development and implementation. This study was supported in part by a grant from the Minnesota Medical Foundation (to DS) and by the Children's Cancer Research Fund. The authors gratefully acknowledge donations to the Animal Cancer Care and Research Program of the University of Minnesota that helped support this project. JFM is supported in part by the Alvin S. and June Perlman Chair in Animal Oncology at the University of Minnesota.

Funding Information:
The authors thank the nursing and technical staff of the Oncology and Surgery Services of the VMC, University of Minnesota for assistance with clinical management of the dogs in this study, Dr. Roy Katz at CustomRx Compounding Pharmacy for assistance compounding SalpIL2, and Drs. Brenda Weigel and Denis Clohisy for assistance with study development and implementation. This study was supported in part by a grant from the Minnesota Medical Foundation (to DS) and by the Children’s Cancer Research Fund. The authors gratefully acknowledge donations to the Animal Cancer Care and Research Program of the University of Minnesota that helped support this project. JFM is supported in part by the Alvin S. and June Perlman Chair in Animal Oncology at the University of Minnesota.

Funding Information:
This study was supported in part by a grant from the Minnesota Medical Foundation (to DS) and by the Children’s Cancer Research Fund. JFM is supported in part by the Alvin S. and June Perlman Chair in Animal Oncology at the University of Minnesota.

Publisher Copyright:
© 2016 The Authors. Veterinary Medicine and Science Published by John Wiley & Sons Ltd.

Keywords

Interleukin-2
Salmonella
canine
immunotherapy
osteosarcoma

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Fritz, S. E., Henson, M. S., Greengard, E., Winter, A. L., Stuebner, K. M., Yoon, U., Wilk, V. L., Borgatti, A., Augustin, L. B., Modiano, J. F., & Saltzman, D. A. (2016). A phase I clinical study to evaluate safety of orally administered, genetically engineered Salmonella enterica serovar Typhimurium for canine osteosarcoma. Veterinary Medicine and Science, 2(3), 179-190. https://doi.org/10.1002/vms3.32

Fritz, SE, Henson, MS , Greengard, E, Winter, AL, Stuebner, KM, Yoon, U, Wilk, VL, Borgatti, A , Augustin, LB , Modiano, JF & Saltzman, DA 2016, 'A phase I clinical study to evaluate safety of orally administered, genetically engineered Salmonella enterica serovar Typhimurium for canine osteosarcoma', Veterinary Medicine and Science, vol. 2, no. 3, pp. 179-190. https://doi.org/10.1002/vms3.32

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title = "A phase I clinical study to evaluate safety of orally administered, genetically engineered Salmonella enterica serovar Typhimurium for canine osteosarcoma",

abstract = "We conducted a prospective phase I study to evaluate safety of an orally administered Salmonella encoding IL-2 (SalpIL2) in combination with amputation and adjuvant doxorubicin for canine appendicular osteosarcoma. Efficacy was assessed as a secondary measure. The first dose of SalpIL2 was administered to 19 dogs on Day 0; amputation was done after 10 days with chemotherapy following 2 weeks later. SalpIL2 was administered concurrent with chemotherapy, for a total of five doses of doxorubicin and six doses of SalpIL2. There were six reportable events prior to chemotherapy, but none appeared due to SalpIL2. Dogs receiving SalpIL2 had significantly longer disease-free interval (DFI) than a comparison group of dogs treated with doxorubicin alone. Dogs treated using lower doses of SalpIL2 also had longer DFI than dogs treated using the highest SalpIL2 dose. The data indicate that SalpIL2 is safe and well tolerated, which supports additional testing to establish the potential for SalpIL2 as a novel form of adjuvant therapy for dogs with osteosarcoma.",

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note = "Funding Information: The authors thank the nursing and technical staff of the Oncology and Surgery Services of the VMC, University of Minnesota for assistance with clinical management of the dogs in this study, Dr. Roy Katz at CustomRx Compounding Pharmacy for assistance compounding SalpIL2, and Drs. Brenda Weigel and Denis Clohisy for assistance with study development and implementation. This study was supported in part by a grant from the Minnesota Medical Foundation (to DS) and by the Children's Cancer Research Fund. The authors gratefully acknowledge donations to the Animal Cancer Care and Research Program of the University of Minnesota that helped support this project. JFM is supported in part by the Alvin S. and June Perlman Chair in Animal Oncology at the University of Minnesota. Funding Information: The authors thank the nursing and technical staff of the Oncology and Surgery Services of the VMC, University of Minnesota for assistance with clinical management of the dogs in this study, Dr. Roy Katz at CustomRx Compounding Pharmacy for assistance compounding SalpIL2, and Drs. Brenda Weigel and Denis Clohisy for assistance with study development and implementation. This study was supported in part by a grant from the Minnesota Medical Foundation (to DS) and by the Children{\textquoteright}s Cancer Research Fund. The authors gratefully acknowledge donations to the Animal Cancer Care and Research Program of the University of Minnesota that helped support this project. JFM is supported in part by the Alvin S. and June Perlman Chair in Animal Oncology at the University of Minnesota. Funding Information: This study was supported in part by a grant from the Minnesota Medical Foundation (to DS) and by the Children{\textquoteright}s Cancer Research Fund. JFM is supported in part by the Alvin S. and June Perlman Chair in Animal Oncology at the University of Minnesota. Publisher Copyright: {\textcopyright} 2016 The Authors. Veterinary Medicine and Science Published by John Wiley & Sons Ltd.",

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AU - Winter, Amber L.

AU - Stuebner, Kathleen M.

AU - Yoon, Una

AU - Wilk, Vicki L.

AU - Borgatti, Antonella

AU - Augustin, Lance B.

AU - Modiano, Jaime F.

AU - Saltzman, Daniel A.

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N2 - We conducted a prospective phase I study to evaluate safety of an orally administered Salmonella encoding IL-2 (SalpIL2) in combination with amputation and adjuvant doxorubicin for canine appendicular osteosarcoma. Efficacy was assessed as a secondary measure. The first dose of SalpIL2 was administered to 19 dogs on Day 0; amputation was done after 10 days with chemotherapy following 2 weeks later. SalpIL2 was administered concurrent with chemotherapy, for a total of five doses of doxorubicin and six doses of SalpIL2. There were six reportable events prior to chemotherapy, but none appeared due to SalpIL2. Dogs receiving SalpIL2 had significantly longer disease-free interval (DFI) than a comparison group of dogs treated with doxorubicin alone. Dogs treated using lower doses of SalpIL2 also had longer DFI than dogs treated using the highest SalpIL2 dose. The data indicate that SalpIL2 is safe and well tolerated, which supports additional testing to establish the potential for SalpIL2 as a novel form of adjuvant therapy for dogs with osteosarcoma.

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A phase I clinical study to evaluate safety of orally administered, genetically engineered Salmonella enterica serovar Typhimurium for canine osteosarcoma

Abstract

Bibliographical note

Keywords

UN SDGs

Access

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