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

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 even...

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Detalles Bibliográficos
Autores principales: Lucroy, Michael D., Clauson, Ryan M., Suckow, Mark A., El-Tayyeb, Ferris, Kalinauskas, Ashley
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672887/
https://www.ncbi.nlm.nih.gov/pubmed/33208160
http://dx.doi.org/10.1186/s12917-020-02675-y
Descripción
Sumario: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.