Development of a flow cytometry assay which allows to evaluate the efficiency of immunomodulatory vaccines to enhance T cell-mediated antitumor response

Autor(es)

Manrique-Rincon, Andrea J. ^{[1, 2]} ; de Carvalho, Anna C. ^[1] ; Eugenia Ribeiro de Camargo, M. ^[1] ; Franchini, Kleber G. ^{[1, 2]} ; Bajgelman, Marcio C. ^{[3, 1, 2]}

Afiliação do(s) autor(es)

^[1] Brazilian Biosci Natl Lab, Ctr Res Energy & Mat, Rua Giuseppe Maximo Scolfaro 10-000, BR-13083100 Campinas, SP - Brazil

^[2] Univ Estadual Campinas, Sch Med, Campinas, SP - Brazil

^[3] Univ Estadual Campinas, Inst Biol, Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Biotechnology; v. 284, p. 11-16, OCT 20 2018.
• Citações Web of Science: 1

Resumo

Immunotherapy has revolutionized the treatment of cancer. Since tumor cells exhibit low immunogenicity and can induce several mechanisms of tolerance, the use of monoclonal antibodies or other immunomodulators, targeting costimulation of T cells may mediate the inhibition of immunosuppressive mechanisms, favouring immune surveillance and enhancing the detection and elimination of tumor cells. We developed a new in vitro assay, based on flow cytometry, which allows exploring the therapeutic potential of tumor-derived immunomodulatory lineages, enhancing anti-tumor response. We generated tumor-derived cells that simultaneously co-express eGFP and one immunomodulatory molecule (OX40L, 4-1BBL or GM-CSF). These genetically modified tumor-derived cells are irradiated and then incubated with primary T cells to evaluate the killing activity, which can be estimated by a decrease in the eGFP positive cells. The results have shown correlation with in vivo experiments. This model may contribute to the development of high-throughput assays for the screening of immunomodulators and a reduction in the use of experimental animals. (AU)

• Processo FAPESP: 17/06692-2 - Desenvolvimento de novos receptores de células T a partir do isolamento de sequências obtidas de linfócitos infiltrados em sítios tumorais, provenientes de animais tratados com imunomoduladores
• Beneficiário: Marcio Chaim Bajgelman
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/02041-6 - Desenvolvimento de uma estratégia de silenciamento transcricional do fator FoxP3 com alvo de inativar células T regulatórias e potenciar resposta imune antitumoral
• Beneficiário: Andrea Johanna Manrique Rincón
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto