Autologous cancer cell vaccination, adoptive T‐cell transfer, and interleukin‐2 administration results in long‐term survival for companion dogs with osteosarcoma
| Autor: | Gayle C. Johnson, Deborah J. Tate, Jeffrey N. Bryan, Dae Young Kim, Gary W. Wood, Carolyn J. Henry, Tammie A. Wahaus, Lindsay L. Donnelly, F. Lynn Sonderegger, Noe Reyes, Sandra M. Bechtel, Brian K. Flesner, Pamela Gayheart‐Walsten |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Oncology
medicine.medical_specialty 040301 veterinary sciences medicine.medical_treatment T-Lymphocytes canine Bone Neoplasms Standard Article 030204 cardiovascular system & hematology interleukin 2 Metastasis 0403 veterinary science 03 medical and health sciences 0302 clinical medicine Dogs Internal medicine osteosarcoma medicine Animals Dog Diseases Prospective Studies leukapheresis Prospective cohort study Chemotherapy lcsh:Veterinary medicine General Veterinary business.industry Vaccination Cancer 04 agricultural and veterinary sciences Immunotherapy Leukapheresis Pets medicine.disease Standard Articles Treatment Outcome Amputation Interleukin-2 lcsh:SF600-1100 Premedication SMALL ANIMAL immunotherapy business |
| Zdroj: | Journal of Veterinary Internal Medicine, Vol 34, Iss 5, Pp 2056-2067 (2020) Journal of Veterinary Internal Medicine |
| ISSN: | 0891-6640 1939-1676 |
| Popis: | Background Osteosarcoma (OSA) in dogs is an aggressive bone tumor with frequent chemotherapy failure and translational relevance for human health. Hypothesis/objectives We hypothesized that dogs with OSA could be treated safely by ex vivo activated T-cells that were generated by autologous cancer vaccination and supported by interleukin-2 (IL-2) treatment with survival more than twice that reported for amputation alone. Animals Osteosarcoma-bearing dogs (n = 14) were enrolled in a single-arm prospective trial after complete staging before amputation. Four healthy dogs also were treated in a safety study. Methods Autologous cancer cell vaccinations were administered intradermally and dogs underwent leukapheresis. Mononuclear cell products were stimulated ex vivo with a T-cell-activating agent. Activated product was transfused and 5 SC IL-2 injections were administered q48h. Dogs were monitored for metastasis by thoracic radiography every 3 months. Results Autologous cancer cell vaccine and activated cellular therapy (ACT) products were successfully generated. Toxicity was minimal after premedicants were instituted before ACT. With premedication, all toxicities were grade I/II. Median disease-free interval for all dogs was 213 days. One dog developed cutaneous metastasis but then experienced spontaneous complete remission. Median survival time for all dogs was 415 days. Five dogs survived >730 days. Conclusions and clinical importance This immunotherapy protocol without cytotoxic chemotherapy is safe and tolerable. Compared to historical amputation reports, survival was notably prolonged in this group of patients. Additional prospective studies are warranted to elucidate active immunologic mechanisms and further improve disease response and survival. |
| Databáze: | OpenAIRE |
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