Canine Cancer Immunotherapeutics

A special issue of Veterinary Sciences (ISSN 2306-7381).

Deadline for manuscript submissions: closed (30 September 2018) | Viewed by 27886

Special Issue Editor


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Guest Editor
Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
Interests: molecular pathogenesis of feline immunodeficiency virus infection; vaccine development in animal models for HIV-1 AIDS; use of cytokines and TLR ligands as vaccine adjuvants; tumor immunology in companion animal cancer
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Dear Colleagues,

Recent studies have revealed the power of immunotherapeutics for human cancer. In particular, agents that activate the immune system by blocking specific anti-inflammatory check points, as well as engineered T cells have proven to be effective in certain human patient populations. However, important issues relating to these therapies must be addressed and include significant toxicities and selection of patients who will most likely respond to these therapeutics. Furthermore, delivery technologies for these drugs warrant further optimization to limit off-target toxicities. Canine cancer patients are likely to benefit from these promising immunotherapeutic modalities, and may also provide a powerful model for testing of new generations of immunotherapeutics. Recent reports within veterinary research describe canine-specific antibodies with potential as checkpoint inhibitors, as well therapeutic canine cancer vaccines with some efficacy. Together these therapeutic modalities may significantly impact therapeutic protocols for certain canine cancers in the future and therefore present a potent area of focus for clinical canine cancer research.

Original manuscripts that address development and testing of cancer immunotherapeutics for canine cancers are solicited for this Special Issue. Studies that use innovative or novel technologies to identify specific cancers or canine patient populations more likely to respond to immunotherapeutics, are also encouraged for submission.

Dr. Ellen E. Sparger
Guest Editor

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Keywords

  • canine cancer
  • cancer immunotherapeutics
  • animal models
  • checkpoint inhibitors
  • engineered T cells
  • cancer vaccines
  • immune system targets
  • immune modulation in cancer
  • immunotherapy toxicities
  • One Health
  • One Medicine

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Published Papers (4 papers)

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Research

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15 pages, 1214 KiB  
Article
The Safety of an Adjuvanted Autologous Cancer Vaccine Platform in Canine Cancer Patients
by Chris Weir, Annika Oksa, Jennifer Millar, Miles Alexander, Nicola Kynoch, Zoe Walton-Weitz, Peter Mackenzie-Wood, Felicia Tam, Hope Richards, Richard Naylor, Katrina Cheng, Peter Bennett, Nikolai Petrovsky and Rachel Allavena
Vet. Sci. 2018, 5(4), 87; https://doi.org/10.3390/vetsci5040087 - 12 Oct 2018
Cited by 10 | Viewed by 11596
Abstract
Canine cancer rates are similar to humans, though the therapeutic options might be limited. Inducing a patient’s own immune system to have an anti-tumor response is an attractive approach to cancer therapy. In this safety study, autologous tumor vaccines produced specifically for each [...] Read more.
Canine cancer rates are similar to humans, though the therapeutic options might be limited. Inducing a patient’s own immune system to have an anti-tumor response is an attractive approach to cancer therapy. In this safety study, autologous tumor vaccines produced specifically for each canine patient were combined with Advax™, a novel non-inflammatory immunomodulator and vaccine adjuvant and were tested for safety in a diverse range of patient presentations alone or in combination with other treatments. Canine patients had their tumor biopsied, debulked or resected and the tumor antigens were processed into an autologous vaccine formulated with Advax™ adjuvant with or without rhizavidin as an additional immune stimulant. Patients treated early in the trial received two intramuscular (IM) doses, 2 weeks apart. As the study progressed and no issues of safety were observed, the protocol was changed to weekly vaccinations for 4 weeks followed by monthly booster shots. Over the 150 I.M injections delivered to date, the vaccine was found to be very safe and no significant adverse reactions were observed. These results justify ongoing development and future controlled studies of this autologous vaccine approach. Full article
(This article belongs to the Special Issue Canine Cancer Immunotherapeutics)
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15 pages, 5490 KiB  
Article
CD147 and Cyclooxygenase Expression in Feline Oral Squamous Cell Carcinoma
by Walaa Hamed Shaker Nasry, Haili Wang, Kathleen Jones, Wessel P. Dirksen, Thomas J. Rosol, Juan Carlos Rodriguez-Lecompte and Chelsea K. Martin
Vet. Sci. 2018, 5(3), 72; https://doi.org/10.3390/vetsci5030072 - 13 Aug 2018
Cited by 12 | Viewed by 5155
Abstract
Feline oral squamous cell carcinoma (OSCC) is a highly invasive form of cancer in cats. In human OSCC, cluster of differentiation 147 (CD147) contributes to inflammation and tumor invasiveness. CD147 is a potential therapeutic target, but the expression of CD147 in feline OSCC [...] Read more.
Feline oral squamous cell carcinoma (OSCC) is a highly invasive form of cancer in cats. In human OSCC, cluster of differentiation 147 (CD147) contributes to inflammation and tumor invasiveness. CD147 is a potential therapeutic target, but the expression of CD147 in feline OSCC has not been examined. Immunohistochemistry was used to determine if cyclooxygenase 2 (COX-2) and CD147 expression in feline OSCC biopsies was coordinated. Tumor cells were more likely to express COX-2 (22/43 cases or 51%) compared to stroma (8/43 or 19%) and adjacent oral epithelium (9/31 cases or 29%) (p < 0.05). CD147 was also more likely to occur in tumor cells compared to stroma and adjacent mucosa, with 21/43 (49%) of cases having >50% tumor cells with mild or moderate CD147 expression, compared to 9/28 (32%) in adjacent epithelium and only 5/43 (12%) in adjacent stroma (p < 0.05). In feline OSCC cell lines (SCCF1, SCCF2, and SCCF3), CD147 gene expression was more consistently expressed compared to COX-2, which was 60-fold higher in SCCF2 cells compared to SCCF1 cells (p < 0.05). CD147 expression did not correlate with COX-2 expression and prostaglandin E2 (PGE2) secretion, indicating that they may be independently regulated. CD147 potentially represents a novel therapeutic target for the treatment of feline OSCC and further study of CD147 is warranted. Full article
(This article belongs to the Special Issue Canine Cancer Immunotherapeutics)
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11 pages, 1380 KiB  
Article
Combination of Suicide and Cytokine Gene Therapies as Surgery Adjuvant for Canine Mammary Carcinoma
by Liliana M. E. Finocchiaro, Agustina I. M. Spector, Lucrecia Agnetti, M. Florencia Arbe and Gerardo C. Glikin
Vet. Sci. 2018, 5(3), 70; https://doi.org/10.3390/vetsci5030070 - 3 Aug 2018
Cited by 8 | Viewed by 4546
Abstract
The incidence of canine mammary carcinoma varies with age, breed, and spay status, being among the main tumors appearing in intact female dogs. Thirty-six canine mammary carcinoma patients received injections of canine interferon-β (cIFN-β) and HSV-thymidine kinase/ganciclovir (HSV-tk/GCV) carrying lipoplexes, into the tumor [...] Read more.
The incidence of canine mammary carcinoma varies with age, breed, and spay status, being among the main tumors appearing in intact female dogs. Thirty-six canine mammary carcinoma patients received injections of canine interferon-β (cIFN-β) and HSV-thymidine kinase/ganciclovir (HSV-tk/GCV) carrying lipoplexes, into the tumor bed, immediately after surgery. Next, they started periodic subcutaneous injections of lipoplexes carrying a human granulocyte-macrophage colony stimulating factor and interleukin-2 mixed with allogeneic mammary carcinoma extracts. This combined strategy was safe and well tolerated. In addition, only two out of 26 patients treated with complete surgery developed a local relapse, and 0 out of 29 stage II and III patients displayed distant metastases, suggesting both local and systemic antitumor activities. The most encouraging result was the long survival times: 22 > 1 year (where 13 > 2 and 4 > 3 years), while maintaining a good quality of life. The preliminary results in five patients presenting with local disease, an additional HSV-tk/GCV plus cIFN-β gene treatment induced local antitumor activity, evidenced by four objective responses (one complete, three partial) and one stable disease. This successful outcome supports further studies to validate this approach not only for canine veterinary patients, but also for translation to human patients. Full article
(This article belongs to the Special Issue Canine Cancer Immunotherapeutics)
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Review

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8 pages, 273 KiB  
Review
Cellular Immunotherapy of Canine Cancer
by Selamawit Addissie and Hans Klingemann
Vet. Sci. 2018, 5(4), 100; https://doi.org/10.3390/vetsci5040100 - 6 Dec 2018
Cited by 20 | Viewed by 5774
Abstract
Infusions with immune cells, such as lymphocytes or natural killer (NK) cells, represent one of several modalities of immunotherapy. In human patients with advanced B-cell leukemia or lymphoma, infusions with chimeric antigen receptor (CAR) T-lymphocytes have shown promising responses. However, the scientific and [...] Read more.
Infusions with immune cells, such as lymphocytes or natural killer (NK) cells, represent one of several modalities of immunotherapy. In human patients with advanced B-cell leukemia or lymphoma, infusions with chimeric antigen receptor (CAR) T-lymphocytes have shown promising responses. However, the scientific and clinical development of cell-based therapies for dogs, who get cancer of similar types as humans, is lagging behind. One reason is that immune cells and their functionality in dogs are less well characterized, largely due a lack of canine-specific reagents to detect surface markers, and specific cytokines to isolate and expand their immune cells. This review summarizes the current status of canine cancer immunotherapies, with focus on autologous and allogeneic T-lymphocytes, as well as NK cells, and discusses potential initiatives that would allow therapies with canine immune cells to “catch up” with the advances in humans. Full article
(This article belongs to the Special Issue Canine Cancer Immunotherapeutics)
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