Autologous cancer cell vaccination, adoptiveT‐cell transfer, and interleukin‐2 administration results in long‐term survival for companion dogs with osteosarcoma

Abstract

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.

Immunotherapy for Dogs: Still Running Behind Humans

“…Those are then ex vivo activated (using a proprietary formula) and expanded. The cell preparation is sent back to the veterinarian for infusion ( 11 ). An update on the study results were recently presented (Bryan, 2020, personal communication) 1 , and if the data hold, this could present a treatment options for dogs with (non-metastatic) osteosarcoma and potentially for other cancers as well.…”

Spontaneously occurring canine cancer as a relevant animal model for developing novel treatments for human cancers

“…Therefore, we cannot deny the possibility that autologous lymphocyte therapy may be effective in preventing relapse in some human cancers [70,71], depending on how it is used. Furthermore, it was recently reported that the use of activated lymphocytes along with autologous tumor cell-derived vaccines after leg amputation in dogs with osteosarcoma not only prolonged survival but also resulted in complete remission of metastatic disease in one case [72].…”

There and back again: Translating adoptive cell therapy to canine cancer and improving human treatment

“…Schematic of cellular immunotherapies used in canine oncology trials. (1) autologous tumour vaccine followed by ex vivo activation and expansion of lymphocytes (Flesner et al 2020) 14 . (2) radiosensitisation prior to autologous NK cell infusion (Canter et al 2017) 15 .…”

“…While TIL clinical trials are lacking in veterinary oncology, researchers associated with the University of Missouri and Elias Animal Health have used a novel approach to adoptive transfer using tumour reactive T cells 14 . Their clinical trial enrolled dogs with osteosarcoma and amputated their limbs, harvesting tumour tissue for the generation of an autologous tumour vaccine.…”