OX40 Monoclonal Antibodies for Treatment of Canine Cancer

Antibody targeting that reduces the need for chemo and radiation therapies
Golden retriever laying down
Opportunity

Available for Licensing
TRL: 4

IP Status

US Patent Pending

Inventors

Steven Dow
Leone Hopkins

Reference No: 18-013
Licensing Manager

Steve Foster
Steve.Foster@colostate.edu
970-491-7100

At a Glance

Researchers at Colorado State University have developed an immunotherapy treatment for canines suffering from osteosarcoma. This treatment involves antibodies specific for the canine OX40 molecule expressed by canine immune cells, which can then activate an immune response. Studies have shown a 60% reduction in tumor volume when using this treatment.

 

Background

Osteosarcoma (OSA) is the most common primary bone tumor in dogs, accounting for 85% of all canine bone cancers. It is stimated that more than 8000 dogs are diagnosed with OSA each year in the United States (3). Curative-intent treatment of osteosarcoma aims to achieve complete tumor control of the primary bone lesion and delay or prevent the onset of metastatic disease. Treatment options with curative intent include amputation or limb-sparing surgery for local tumor control followed by adjuvant chemotherapy for systemic disease. Other treatment options include the use of immunomodulators and high-dose radiation therapy (4).

Overview

The antibody developed herein targets the OX40, a glycoprotein mainly found on immune T-cells and is involved in the migration of activated T-cells into tissues following inflammatory signals. It is considered an immune checkpoint, and certain cancers develop by evading the immune system activation. Antibody activation of immune cells has shown promise for treating human and animal diseases, by stimulating an immune response from native T-cells. The OX40 antibody developed has exhibited delayed tumor growth and decreased tumor cell volume compared to a placebo group and an alternate immune checkpoint in animal models of OSA. Further, when combined with Stereotactic Body Radiotherapy (SBRT), OX40 immunotherapy modifies immunological effects locally and systemically (5). 

 

This technology may also prove useful in the development of immunotherapy drugs for human diseases and cancers, due to similar immune system and immune responses between dogs and humans (1). Thus, the antibody developed here may prove useful in the study of immune responses and oncology (2).

A bar graph
Figure 1: Serum cytokine responses associated with SBRT or SBRT and immunotherapy. Fold change in serum cytokine levels post-treatment relative to pre-treatment for dogs treated with SBRT or SBRT + immunotherapy. * p = 0.035 (SBRT n = 6, SBRT and immunotherapy n

 

Benefits
  • Specific antibody targeting the activation of immune cells reduces need for chemotherapy and radiation therapy
  • Prevents metastatic growth
  • Reduces side effects associated with current cancer treatment options
  • 60% reduction in tumor volume in animals models, compared with placebo and an alternative immune checkpoint
  • Simple administration of medication
Applications
  • Treatment of canine osteosarcoma
  • Treatment of other cancers sensitive to OX40 activation
  • Treatment of chronic infections in canines
  • Model for studying human immunotherapy and drug development

Publications

References

(1) Dow, Steven. “A Role for Dogs in Advancing Cancer Immunotherapy Research.” Frontiers in Immunology, vol. 10, 17 Jan. 2020, https://doi.org/10.3389/fimmu.2019.02935 .

(2) Mueller, F, et al. “Comparative Biology of Human and Canine Osteosarcoma.” Anticancer Research, vol. 27, no. 1A, Jan. 2007, https://doi.org/https://ar.iiarjournals.org/content/anticanres/27/1A/155.full.pdf.

(3) Schwartz, Anthony L., et al. “Orthotopic Model of Canine Osteosarcoma in Athymic Rats for Evaluation of Stereotactic Radiotherapy.” American Journal of Veterinary Research, vol. 74, no. 3, 2013, pp. 452–458., https://doi.org/10.2460/ajvr.74.3.452.

(4) Walter, C. U., et al. “Curative-Intent Radiation Therapy as a Treatment Modality for Appendicular and Axial Osteosarcoma: A Preliminary Retrospective Evaluation of 14 Dogs with the Disease.” Veterinary and Comparative Oncology, vol. 3, no. 1, 2005, pp. 1–7., https://doi.org/10.1111/j.1476-5810.2005.00062.x.

(5) Dow, S. et al. “Immunologic Effects of Stereotactic Body Radiotherapy in Dogs with Spontaneous Tumors and the Impact of Intratumoral OX40/TLR Agonist Immunotherapy.” International Journal of Molecular Sciences, 2022, 23, 826. https://doi.org/10.3390/ijms23020826

Last updated: October 2022