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

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

doi:10.1002/vms3.32

Cited by 50 publications

(27 citation statements)

References 45 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…98 Oral administration of Salmonella typhimurium genetically engineered to express human IL-2 to dogs also appeared to be safe and well tolerated. 116 Bacille Calmette-Guérin (BCG), attenuated Mycobacterium bovis, has also been administered to dogs with OSA and may improve survival, although the mechanisms of immune response to BCG are not completely understood. 91,92 xenogeneic hamster cells modified to secrete human GM-CSF and IL-2.…”

Section: Veterinary Clinical Trialsmentioning

confidence: 99%

Sarcomas—A barren immunological wasteland or field of opportunity for immunotherapy?

Atherton

Lenz

Mason

2020

Vet Comparative Oncology

View full text Add to dashboard Cite

Key advances in our understanding of immunobiology and the immunosuppressive mechanisms of the tumour microenvironment have led to significant breakthroughs in manipulating the immune system to successfully treat cancer. Remarkable therapeutic responses have occurred with tumours that carry a high mutational burden. In these cases, pre-existing tumour-specific T cells can be rejuvenated via checkpoint inhibition to eliminate tumours. Furthermore, durable remissions have been achieved in haematological malignancies following adoptive transfer of T cells that specifically target cell surface proteins where expression is restricted to the malignancy's cell of origin. Soft tissue sarcomas and bone sarcomas have a paucity of non-synonymous somatic mutations and do not commonly express known, targetable, tumour-specific antigens. Historically, soft tissue sarcomas have been considered immunologically 'cold' and as such, unlikely candidates for immune therapy. Here, we review the immune landscape of canine and feline sarcomas and the immunotherapeutic strategies that have been employed in veterinary clinical trials to improve patient outcome. We also provide insight into immunotherapeutic approaches being used to treat human sarcomas. Together, current data indicates that, rather than a barren immunological wasteland, sarcomas represent a field of opportunities for immunotherapies. Furthermore, we and others would suggest that strategic combinations of immunotherapeutic approaches may hold promise for more effective treatments for high grade soft tissue sarcomas and bone sarcomas.

show abstract

Section: Veterinary Clinical Trialsmentioning

confidence: 99%

Sarcomas—A barren immunological wasteland or field of opportunity for immunotherapy?

Atherton

Lenz

Mason

2020

Vet Comparative Oncology

View full text Add to dashboard Cite

show abstract

“…Despite the complex safety considerations, the FDA has allowed several clinical trials with tumor-targeting bacteria and bacterial vaccines designed to elicit a systemic response (Table 4 ) [ 10 , 149 – 152 ]. Clinical studies on companion dogs with spontaneous tumors have also been conducted [ 10 , 153 , 154 ]. The tumor-targeting bacterial strains tested in both canine and human studies showed reasonable safety profiles in general and promising antitumor activities in some studies.…”

Section: Lessons Learned From Clinical Studiesmentioning

confidence: 99%

White paper on microbial anti-cancer therapy and prevention

Forbes¹,

Coffin²,

Deng³

et al. 2018

j. immunotherapy cancer

Self Cite

122

View full text Add to dashboard Cite

In this White Paper, we discuss the current state of microbial cancer therapy. This paper resulted from a meeting (‘Microbial Based Cancer Therapy’) at the US National Cancer Institute in the summer of 2017. Here, we define ‘Microbial Therapy’ to include both oncolytic viral therapy and bacterial anticancer therapy. Both of these fields exploit tumor-specific infectious microbes to treat cancer, have similar mechanisms of action, and are facing similar challenges to commercialization. We designed this paper to nucleate this growing field of microbial therapeutics and increase interactions between researchers in it and related fields. The authors of this paper include many primary researchers in this field. In this paper, we discuss the potential, status and opportunities for microbial therapy as well as strategies attempted to date and important questions that need to be addressed. The main areas that we think will have the greatest impact are immune stimulation, control of efficacy, control of delivery, and safety. There is much excitement about the potential of this field to treat currently intractable cancer. Much of the potential exists because these therapies utilize unique mechanisms of action, difficult to achieve with other biological or small molecule drugs. By better understanding and controlling these mechanisms, we will create new therapies that will become integral components of cancer care.

show abstract

“…A phase I trial of VNP20009 was performed in dogs with a variety of malignancies and 41 dogs received intravenous administration of VNP20009 at escalating doses weekly or biweekly with an objective and biological overall response rate of 15% and 37%, respectively . A prospective phase I study of 19 dogs was also performed to evaluate safety of an orally administered Salmonella encoding IL‐2 (SalpIL2) in combination with amputation and adjuvant doxorubicin chemotherapy for canine appendicular osteosarcoma . While SalpIL2 was well tolerated, it did not provide a clear benefit compared with a historical control group of dogs treated with amputation and adjuvant doxorubicin/carboplatin …”

Section: Immunotherapy Approaches For Canine Sarcomasmentioning

confidence: 99%

“…A prospective phase I study of 19 dogs was also performed to evaluate safety of an orally administered Salmonella encoding IL‐2 (SalpIL2) in combination with amputation and adjuvant doxorubicin chemotherapy for canine appendicular osteosarcoma . While SalpIL2 was well tolerated, it did not provide a clear benefit compared with a historical control group of dogs treated with amputation and adjuvant doxorubicin/carboplatin …”

Section: Immunotherapy Approaches For Canine Sarcomasmentioning

confidence: 99%

Emerging therapeutic approaches for canine sarcomas: Pushing the boundaries beyond the conventional

Borgatti

Dickerson

Lawrence

2019

Vet Comparative Oncology

Self Cite

View full text Add to dashboard Cite

Sarcomas represent a group of genomically chaotic, highly heterogenous tumours of mesenchymal origin with variable mutational load. Conventional therapy with surgery and radiation therapy is effective for managing small, low‐grade sarcomas and remains the standard therapeutic approach. For advanced, high‐grade, recurrent, or metastatic sarcomas, systemic chemotherapy provides minimal benefit, therefore, there is a drive to develop novel approaches. The discovery of “Coley's toxins” in the 19th century, and their use to stimulate the immune system supported the application of unconventional therapies for the treatment of sarcomas. While promising, this initial work was abandoned and treatment paradigm and disease course of sarcomas was largely unchanged for several decades. Exciting new therapies are currently changing treatment algorithms for advanced carcinomas and melanomas, and similar approaches are being applied to advance the field of sarcoma research. Recent discoveries in subtype‐specific cancer biology and the identification of distinct molecular targets have led to the development of promising targeted strategies with remarkable potential to change the landscape of sarcoma therapy in dogs. The purpose of this review article is to describe the current standard of care and limitations as well as emerging approaches for sarcoma therapy that span many of the most active paradigms in oncologic research, including immunotherapies, checkpoint inhibitors, and drugs capable of cellular metabolic reprogramming.

show abstract

A phase I clinical study to evaluate safety of orally administered, genetically engineeredSalmonella entericaserovarTyphimuriumfor canine osteosarcoma

Cited by 50 publications

References 45 publications

Sarcomas—A barren immunological wasteland or field of opportunity for immunotherapy?

Sarcomas—A barren immunological wasteland or field of opportunity for immunotherapy?

White paper on microbial anti-cancer therapy and prevention

Emerging therapeutic approaches for canine sarcomas: Pushing the boundaries beyond the conventional

Contact Info

Product

Resources

About