Abstract 2824: In vitro tumor killing assays for predicting cellular therapeutic efficacy
| العنوان: | Abstract 2824: In vitro tumor killing assays for predicting cellular therapeutic efficacy |
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| المؤلفون: | Enrique Garcia-Alvarez, Robert Nunan, Jezrom Self-Fordham, Michelle Yap, Anna Pascoe, Marie Carkill, S. Rhiannon Jenkinson, Louise Brackenbury |
| المصدر: | Cancer Research. 80:2824-2824 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Cancer Research, Oncology |
| الوصف: | Cellular immunotherapy is emerging as a fifth pillar of cancer treatment. Clinical efficacy has been proven for a variety of cancers; however, its true potential has yet to be unlocked. Development of reliable and mechanistically appropriate in vitro screening assays that recapitulate in vivo immune-tumor interactions have been outpaced by in vivo living cell therapy efficacy models. Here we describe a range of in vitro primary human assays to model tumor killing by immune cells. This platform addresses multiple anti-tumor immune effector pathways and has been validated with standard of care therapeutics. Fluorescently labelled target cells (PDX-cell lines, tumor cell lines or human primary/iPSC derived cells) screened for relevant antigen expression were cultured in monolayer or spheroid forms and co-cultured with the cellular therapeutic. On target killing by effectors is driven by binding of the TCR or CAR to its cognate antigen (MHC/peptide or protein, respectively) with readouts of cell killing utilising live cell imaging (IncuCyte) and flow cytometry based approaches to measure target cell growth and apoptosis. Additional analysis of soluble mediators can determine the extent of effector cell activation. To discriminate between ‘on' and ‘off' target killing by cellular therapeutics, primary/iPSC-derived normal cell types representative of different tissue types were screened for expression of an HLA subtype capable of binding exogenously applied tumor-associated antigen (TAA) prior to co-culture. Under these conditions in the case of a TCR based cellular therapeutic, efficacy can be screened for, or in the absence of the putative TAA expression, the extent of off-target killing determined. Enhancement of tumor targeting and killing by immune cells is an attractive therapeutic modality partly due to the clinical success of checkpoint inhibitors which can enhance the activation and effector function of endogenous T/NK cells or cellular therapeutics. The presented data highlight the importance of assays which can recapitulate tumor-immune interactions and include immune effector pathways known to potentiate anti-tumor immune responses. These assays represent valuable screening tools capable of informing cellular therapeutic target selection and refinement before moving to more complex in vivo models. Citation Format: Robert Nunan, Michelle Yap, Enrique Garcia-Alvarez, Marie Carkill, Anna Pascoe, Louise Brackenbury, Jezrom Self-Fordham, S. Rhiannon Jenkinson. In vitro tumor killing assays for predicting cellular therapeutic efficacy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2824. |
| تدمد: | 1538-7445 0008-5472 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::e3d886fd9832541ae2b21aa64cbcc12a https://doi.org/10.1158/1538-7445.am2020-2824 |
| رقم الأكسشن: | edsair.doi...........e3d886fd9832541ae2b21aa64cbcc12a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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