Abstract 4833: Perfusion-based bioreactor culture of primary cancer tissue maintains tumor microenvironment complexity and allow in-vitro testing of immune blockade therapy

Abstract

Abstract In vitro culture of primary cancer tissue is still very limited and the generation of patient derived xenograft determine the loss of human-cancer associated stroma. In this context, the use of 3D in vitro systems based on human tissue may be an innovative system to be exploited for keeping the tumor microenvironment (TME) complexity of the tissue in vitro. Freshly excised colorectal (CRC) and breast cancer (BrCa) specimens were fragmented and cultured in 3D “sandwich-like format” between porous collagen scaffolds under perfusion flow (U-CUP, Cellec Biotek AG). The maintenance of tumor and immune-infiltrating cells, survival and phenotypic characterization were histologically assessed. In a second step cancer treatment were tested. U-CUP culture allowed the preservation, viability and expansion of tumor tissue with concomitant stromal and immune cells. Expanding cancer cells were viable after 10 and 21 days (CRC and BrCa, respectively). Administration of anti-ER treatment to Lumina A ER+ BrCa was associated with decreased expansion of cancer tissue into the scaffold after 21 days. The maintenance of immune-infiltrating cells allowed testing of immune blockade therapy. Administration of anti-PDL1 antibody, alone or in combination with anti-CTLA4, to the culture medium was associated with increased expression of markers of immune-activation (i.e. IFNγ) and decreased expression of immunosuppressive cytokine IL10. Preserving malignant, interstitial and immunocompetent cells comprised in surgically excised tumor specimens might allow a direct evaluation of the effects of various treatments on the complex TME. This engineered in vitro model could allow animal-free testing and it could be extended as a platform allowing the testing of innovative approaches for the treatment of human malignancies. Our findings shed the light on a promising system for selecting personalized treatment based on a patient’s tumor specific microenvironment. Note: This abstract was not presented at the meeting. Citation Format: Manuele Giuseppe Muraro, Simone Muenst, Celeste Manfredonia, Valentina Mele, Silvio Daester, Alexandar Tzankov, Luigi Terracciano, Walter Weber, Giulio C. Spagnoli, Giandomenica Iezzi, Ivan Martin, Savas D. Soysal. Perfusion-based bioreactor culture of primary cancer tissue maintains tumor microenvironment complexity and allow in-vitro testing of immune blockade therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4833. doi:10.1158/1538-7445.AM2017-4833