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Priming of pancreatic cancer cells with bispecific antibody armed activated T cells sensitizes tumors for enhanced chemoresponsiveness.
Thakur, Archana; Ung, Johnson; Tomaszewski, Elyse N; Schienschang, Amy; LaBrie, Timothy M; Schalk, Dana L; Lum, Lawrence G.
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  • Thakur A; Department of Medicine, Division of Hematology and Oncology, University of Virginia Cancer Center, Charlottesville, Virginia, USA.
  • Ung J; Department of Medicine, Division of Hematology and Oncology, University of Virginia Cancer Center, Charlottesville, Virginia, USA.
  • Tomaszewski EN; Department of Oncology, Barbara Ann Karmanos Cancer Institute and Wayne State University, Detroit, Michigan, USA.
  • Schienschang A; Department of Medicine, Division of Hematology and Oncology, University of Virginia Cancer Center, Charlottesville, Virginia, USA.
  • LaBrie TM; Department of Medicine, Division of Hematology and Oncology, University of Virginia Cancer Center, Charlottesville, Virginia, USA.
  • Schalk DL; Department of Medicine, Division of Hematology and Oncology, University of Virginia Cancer Center, Charlottesville, Virginia, USA.
  • Lum LG; Department of Medicine, Division of Hematology and Oncology, University of Virginia Cancer Center, Charlottesville, Virginia, USA.
Oncoimmunology ; 10(1): 1930883, 2021 06 01.
Article en En | MEDLINE | ID: mdl-34123574
In this study, we investigated the ability of bispecific antibody armed activated T cells to target drug resistant pancreatic cancer cells and whether or not "priming" these resistant cancer cells with bispecific antibody armed activated T cells could enhance subsequent responsiveness to chemotherapeutic drugs. Chemotherapeutic responses for pancreatic cancer are either limited or the tumors develop resistance to chemotherapy regimens. The impetus for this study was the remarkable clinical response seen in our earlier phase I/II clinical trial: a pancreatic cancer patient with drug resistant tumors who showed progression of disease following three infusions of anti-CD3 x anti-EGFR bispecific antibody armed activated T cells (EGFR BATs) was restarted on the initial low dose of 5-fluorouracil showed complete response, suggesting that BATs infusions may have sensitized patient's tumor for chemoresponsiveness. In the current study, we tested the hypothesis that BATs can sensitize tumors for chemoresponsiveness. Gemcitabine or cisplatin-resistant MiaPaCa-2 and L3.6 cell lines were effectively targeted by EGFR BATs. Priming of drug sensitive or resistant cells with EGFR BATs followed by retargeting with lower concentrations of 50% inhibitory concentration of gemcitabine or cisplatin showed enhanced cytotoxicity. Gemcitabine or cisplatin-resistant cell lines show an increased proportion of CD44+/CD24+/EpCAM+ cancer stem like cells as well as an increased number of ABC transporter ABCG2 positive cells compared to the parental cell lines. These data suggest that bispecific antibody armed activated T cells can target and kill chemo-resistant tumor cells and also markedly augment subsequent chemotherapeutic responsiveness, possibly by modulating the expression of ABC transporters.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Anticuerpos Biespecíficos Límite: Humans Idioma: En Revista: Oncoimmunology Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Anticuerpos Biespecíficos Límite: Humans Idioma: En Revista: Oncoimmunology Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos