Biology Reconstructed: Testing Immuno-Oncology Agents In Tumor-Specific 3D Cell Culture

Mukti R. Parikh and Julia Kirshner
AACR Virtual Annual Meeting 2020
Here we describe a tumor-specific 3D cell culture platform where the human tumor microenvironment is reconstructed ex vivo. Our 3D tumor-specific models incorporate tissue-specific extracellular matrix(ces) (ECM) and tumor-specific medium supplements allowing for a true reconstruction of tumor microenvironment. Our approach is compatible with multiple classes of immuno-oncology agents from naked antibodies and antibody-drug conjugates, to bi- and tri-specific compounds, and CAR-T cells.
Reconstructed Bone (r-Bone): A Patient-Derived 3D Culture Platform For Prediction Of Clinical Outcomes In Multiple Myeloma

Amrita Krishnan, Nitya Nathwani, Michael Rosenzweig, Chatchada Karanes, Myo Htut, Sahebi Firoozeh, Steven Rosen, Julia Kirshner
AACR Virtual Annual Meeting 2020

In this study, we aimed to evaluate the capacity of the Reconstructed Bone (r-Bone) model to predict clinical outcomes in patients with multiple myeloma. r-Bone cultures correctly predicted the outcome of 19 out of 21 cases. This data demonstrate that the r-Bone system could be used for pipeline attrition management to select drug candidates with the highest probability of clinical success and can be developed into a prognostic tool for the selection of treatment regimen for patients with multiple myeloma.

1α,25-Dihydroxyvitamin D Inhibits the Metastatic Capability of MCF10CA1a and MDA-MB-231 Cells in an In Vitro Model of Breast to Bone Metastasis.
Wilmanski T, Barnard A, Parikh MR, Kirshner J, Buhman K, Burgess J, Teegarden D
Nutrition and Cancer
2016 68(7):1202-9

Maytansinoid immunoconjugate IMGN901 is cytotoxic in a three-dimensional culture model of multiple myeloma. 
Nierste BA, Gunn EJ, Whiteman KR, Lutz RJ, Kirshner J
American Journal of Blood Research
2016 18;6(1):6-18

A reconstructed metastasis model to recapitulate the metastatic spread in vitro. 
Parikh MR, Minser KE, Rank LM, Glackin CA, Kirshner J
Biotechnology Journal
2014 9(9):1129-39

Differentiation of cancer cells in two-dimensional and three-dimensional breast cancer models by Raman spectroscopy. 
Damayanti NP, Fang Y, Parikh MR, Craig AP, Kirshner J, Irudayaraj J
Journal of Biomedical Optics
2013 18(11):117008

The natural products parthenolide and andrographolide exhibit anti-cancer stem cell activity in multiple myeloma. 
Gunn EJ, Williams JT, Huynh DT, Iannotti MJ, Han C, Barrios FJ, Kendall S, Glackin CA, Colby DA, Kirshner J
Leukemia & Lymphoma
2011 52(6):1085-97

In a patient with biclonal Waldenstrom macroglobulinemia only one clone expands in three-dimensional culture and includes putative cancer stem cells. 
Kirshner J, Thulien KJ, Kriangkum J, Motz S, Belch AR, Pilarski LM
Leukemia & Lymphoma
2011 52(2):285-9

A unique three-dimensional model for evaluating the impact of therapy on multiple myeloma. 
Kirshner J, Thulien KJ, Martin LD, Debes Marun C, Reiman T, Belch AR, Pilarski LM
2008 112(7):2935-45

Mutation analysis of the short cytoplasmic domain of the cell-cell adhesion molecule CEACAM1 identifies residues that orchestrate actin binding and lumen formation. 
Chen CJ, Kirshner J, Sherman MA, Hu W, Nguyen T, Shively JE
Journal of Biological Chemistry
2007 282(8):5749-60

CEACAM1, a cell-cell adhesion molecule, directly associates with annexin II in a three-dimensional model of mammary morphogenesis. 
Kirshner J, Schumann D, Shively JE
Journal of Biological Chemistry
2003 278(50):50338-45

CEACAM1-4S, a cell-cell adhesion molecule, mediates apoptosis and reverts mammary carcinoma cells to a normal morphogenic phenotype in a 3D culture. 
Kirshner J, Chen CJ, Liu P, Huang J, Shively JE Proc Proceedings of the National Academy of Sciences
2003 100(2):521-6


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