Evaluation of an autologous cancer vaccine for the treatment of metastatic canine hemangiosarcoma: a preliminary study

Abstract

Background Canine hemangiosarcoma (HSA) is an aggressive cancer arising from multipotential bone marrow-derived stem cells. Anthracycline chemotherapy drugs have been the mainstay adjuvant chemotherapy following surgery with only modest improvement in survival and an attendant risk for adverse events. Immunotherapy, using a whole cell autologous cancer vaccine adjuvanted with MIM-SIS, may improve outcomes for dogs with HSA with a lower risk for adverse events compared with chemotherapy. Results In cultured DH82 canine monocyte-like cells, autologous cancer vaccines prepared from 13 dogs with HSA increased MHC-II surface expression ranging from 20.0-60.4% on single-stained cells, CD80 surface expression ranging from 23.7–45.9% on single-stained cells, and MHC-II/CD80 surface expression ranging from 7.2–20.1% on double-stained cells. Autologous cancer vaccines were able to, on average, stimulate an up-regulation of MHC-II and CD80 by 48-fold as compared to media only (MHC-II + CD80 + cells: 12.19 ± 3.70% vs. 0.25 ± 0.06%; p < 0.001). The overall median survival time for dogs treated with the autologous cancer vaccine was 142 days (range, 61 to 373 days). Dogs treated with the autologous cancer vaccine or maximum tolerated dose (MTD) chemotherapy had significantly (P < 0.001) longer survival than dogs treated with surgery alone. The 1-year survival rate was 12.5% for dogs treated with the autologous cancer vaccine, and 0% for dogs treated with surgery alone or MTD chemotherapy. No adverse events were observed in the dogs treated with the autologous cancer vaccine. Conclusions The adjuvanted autologous cancer vaccine is capable of up-regulating MHC-II and CD80 in cultured canine monocyte-derived cells, which are important stimulatory molecules in generating an immune response and improves survival time in dogs with metastatic (stage III) HSA when compared to surgical treatment alone. Autologous cancer vaccine-treated dogs had survival similar to those dogs treated with MTD chemotherapy without any observed adverse events. This autologous cancer vaccine represents an effective form of individualized immunotherapy that is an appealing option for dog owners not wanting to pursue adjuvant chemotherapy for HSA.

Investigation of Prognostic Value of Claudin-5, PSMA, and Ki67 Expression in Canine Splenic Hemangiosarcoma

“…Samples with expression equal to or lower than the mean value were classified as low expression, and samples with expression higher than the mean value were classified as high. Since adjuvant treatment can affect the OS of patients [2,6,9], we evaluated samples from canine patients that underwent only surgery and surgery associated with chemotherapy separately. Moreover, among the patients that underwent chemotherapy, we grouped patients treated with anthracycline-based chemotherapy and metronomic cyclophosphamide.…”

“…It is one of the most aggressive and metastatic cancers in dogs [1][2][3][4][5]. It affects middle-aged to elderly dogs, with a greater predisposition for males [1][2][3][4][5][6][7][8]. The most common metastatic sites are the liver and lungs, and less frequently the omentum, kidneys, retroperitoneum, and skin [5][6][7][8][9][10][11][12][13].…”

“…It affects middle-aged to elderly dogs, with a greater predisposition for males [1][2][3][4][5][6][7][8]. The most common metastatic sites are the liver and lungs, and less frequently the omentum, kidneys, retroperitoneum, and skin [5][6][7][8][9][10][11][12][13]. Despite the importance of this tumor in clinical practice, few advances have been achieved recently regarding prognosis and treatment of this tumor subtype [6].…”

“…The most common metastatic sites are the liver and lungs, and less frequently the omentum, kidneys, retroperitoneum, and skin [5][6][7][8][9][10][11][12][13]. Despite the importance of this tumor in clinical practice, few advances have been achieved recently regarding prognosis and treatment of this tumor subtype [6]. Splenectomy is the gold standard treatment for splenic has.…”

“…Splenectomy is the gold standard treatment for splenic has. However, due to poor outcomes, adjuvant chemotherapy is associated with controversial results [5][6][7][8][9][10][11][12][13].…”