Intra-arterial cisplatin with or without radiation in limb-sparing for canine osteosarcoma

Withrow, Stephen J.; Thrall, Donald E.; Straw, Rodney C.; Powers, Barbara E.; Wrigley, Robert; LaRue, Susan M.; Page, Rodney L.; Richardson, Daniel C.; Bissonette, K. W.; Betts, C. W.; DeYoung, David J.; Richter, Swetlana; Jameson, Vicki J.; George, Stephen L.; Dodge, Richard K.; Gillette, Edward L.; Douple, Evan B.

doi:10.1002/1097-0142(19930415)71:8<2484::aid-cncr2820710810>3.0.co;2-d

Cited by 85 publications

(74 citation statements)

References 39 publications

(13 reference statements)

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“…Among canine malignancies, osteosarcoma (OS) has a high incidence, affecting roughly 8,000 dogs per year in the US. 8 Recent sequencing of the canine genome and molecular studies have revealed that canine OS not only mimics human disease clinically, but also shares common genetic mutations/gene rearrangements found in humans, particularly human epidermal growth factor receptor 2 (HER2). 9,10 …”

Section: Introductionmentioning

confidence: 99%

Toward Immunotherapy With Redirected T Cells in a Large Animal Model

Mata

Vera

Gerken

et al. 2014

Journal of Immunotherapy

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Adoptive transfer of T cells expressing chimeric antigen receptors (CARs) has shown promising anti-tumor activity in early phase clinical studies, especially for hematological malignancies. However, most preclinical models do not reliably mimic human disease. We reasoned that developing an adoptive T-cell therapy approach for spontaneous osteosarcoma (OS) occurring in dogs would more closely reproduce the condition in human cancer. To generate CAR-expressing canine T cells we developed expansion and transduction protocols that allow for the generation of sufficient numbers of CAR-expressing canine T cells for future clinical studies in dogs within 2 weeks of ex vivo culture. To evaluate the functionality of CAR-expressing canine T cells we targeted HER2-positive OS. We demonstrate that canine OS is positive for HER2, and that canine T cells expressing a HER2-specific CAR with human-derived transmembrane and CD28.ζ signaling domains recognize and kill HER2-positive canine OS cell lines in an antigen-dependent manner. To reduce the potential immunogenicity of the CAR we evaluated a CAR with canine-derived transmembrane and signaling domains, and found no functional difference between human and canine CARs. Hence, we have successfully developed a strategy to generate CAR-expressing canine T cells for future preclinical studies in dogs. Testing T-cell therapies in an immunocompetent, outbred animal model may improve our ability to predict their safety and efficacy prior to conducting studies in humans.

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Section: Introductionmentioning

confidence: 99%

Toward Immunotherapy With Redirected T Cells in a Large Animal Model

Mata

Vera

Gerken

et al. 2014

Journal of Immunotherapy

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“…Crucially, they capture critical clinical features of the disease, such as diffuse pulmonary metastasis [117]. Using such models, Ranieri et al correctly predicted the efficacy of a regime based on intra-arterial cisplatin and irradiation to achieve local tumor control and retain limb function [118,119]. Canine studies are, however, largely prohibitive in terms of costs and scale, severely limiting their routine application in research studies.…”

Section: Primary Bone Malignancymentioning

confidence: 99%

Human Bone Xenografts: from Preclinical Testing for Regenerative Medicine to Modeling of Diseases

Chong

Bao

et al. 2016

Curr Mol Bio Rep

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Xenografting involves the transplantation of human tissue or cells into animal models and is an important tool for regenerative medicine research. Implantation of engineered human bone tissues into animal models, for example, is performed in preclinical evaluations of product safety and efficacy. With the advent of improved experimental methodologies, these models are further being exploited to interrogate molecular mechanisms and physiological interactions in vivo. In parallel to these developments, patient-derived xenograft murine models of cancer are increasingly being studied for various applications in cancer research and therapy; it follows that xenograft models in tissue engineering may be adapted for such approaches. In this review, we first discuss the development of human bone xenograft models to recapitulate physiological states in regenerative medicine. Subsequently, we discuss the use of these techniques for applications in modeling pathological states in skeletal oncology, namely, hematopoietic malignancies, bone metastatic disease, and primary bone malignancy.

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“…As part of a subsequent NCI-sponsored randomized clinical trial in dogs with OS, it proved to be technically feasible, safe, and effective in treating the disease (Withrow et al 1993). Based in part on these fi ndings, the number of preoperative cycles of IA Pt was further refi ned in humans.…”

Section: Intra-arterial Chemotherapymentioning

confidence: 99%

“…Osteosarcoma has long been thought to be radiation "resistant," but studies of canine OS have shown a dose response for fractionated external beam radiation and indicated that cisplatin was at least additive if not synergistic with radiation on local tumor cell kill (Withrow et al 1993). When combined with cisplatin, the radiation doses required to induce over 80% local necrosis can be reduced below those that cause host bone necrosis.…”

Section: Radiation Strategies For Osteosarcomamentioning

confidence: 99%

Cross Talk from Pets to People: Translational Osteosarcoma Treatments

Withrow¹,

Wilkins²

2010

ILAR Journal

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Osteosarcoma is almost identical in companion animals and in people, so research in basic cancer biology and treatment is readily translational across the species. In this article the authors (one DVM and one MD) present examples of species "cross talk" based on their parallel careers in musculoskeletal oncology surgery. Dogs in particular provide a relevant osteosarcoma model that is 10 times more prevalent than the corresponding human condition and offers a unique opportunity to answer questions related to local tumor control and metastasis. Advantages of the dog model include spontaneous development of the disease; the animal's large size, intact immune system, shared genetic aberrations, and response to traditional chemotherapies; and owners' acceptance and compliance with clinical trials for their pets. We describe several cross-species treatment strategies for osteosarcoma--chemotherapy, limb-sparing techniques, and radiation--as well as surprising impacts of infection and immunology. We conclude with some discussion of areas for further discovery and development to advance species cross talk in support of One Health.

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Intra-arterial cisplatin with or without radiation in limb-sparing for canine osteosarcoma

Cited by 85 publications

References 39 publications

Toward Immunotherapy With Redirected T Cells in a Large Animal Model

Toward Immunotherapy With Redirected T Cells in a Large Animal Model

Human Bone Xenografts: from Preclinical Testing for Regenerative Medicine to Modeling of Diseases

Cross Talk from Pets to People: Translational Osteosarcoma Treatments

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