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Advancing Immuno-Oncology:

Catalyzing cell-based therapies

 

IMMUNO-ONCOLOGY

Identification and selection of specific immune cells is key to maximize efficacy and minimize unwanted side effects of personalized cell-based therapies. Efficacy and specificity of cell-based therapeutics, such as CAR-T cells, is determined by tumor cell/T-cell, and cell/matrix interactions.

Through multiparametric analysis of complex interactions in a physiologically relevant context and at single-cell resolution, EVORION technology catalyzes the development of cell-based therapies. Individual cells from a heterogeneous population of therapeutic T-cells are paired with tumor cells and analyzed for their efficacy and specificity in killing tumor cells. Selected T-cells can then be expanded for further analyses and, eventually, for therapeutic applications.

 

TUMOR EVOLUTION AND TUMOR CELL HETEROGENEITY

Tumor cell heterogeneity is one of the major challenges in the development of personalized cancer therapies. Within a tumor, cells are organized hierarchically, steered by ‘‘stem-like cells’’ that drive tumor growth, mediate metastasis, and contribute to treatment resistance[1]. Malignant tumors become therapy-resistant through “tumor evolution”—a combination of genetic alterations and epigenetic events that change the constitution and function of tumor and surrounding cells.

EVORION technology provides insight into tumor cell heterogeneity from both non-solid and solid tumors through time-resolved analyses of heterogeneous cell populations at single-cell resolution. Understanding tumor evolution and tumor cell heterogeneity opens new diagnostic dimensions that are key for the development of innovative and personalized therapies.

LIQUID BIOPSY

Circulating tumor cells (CTCs) originate from a tumor and circulate inside the blood or lymphatic system. CTCs can cause metastases, a process responsible for the majority of cancer-related deaths[2]. Efficient characterization, selection, and manipulation of CTCs is extremely challenging, as they are present at very low concentrations (ca. 1–10 CTC per mL of whole blood)[3], but the extreme sensitivity of the EVORION technology enables the selection and analysis of individual CTCs from liquid biopsy samples. The resulting insights about individual CTC pheno- and genotype will significantly impact cancer diagnostics and prognosis[4].

 

REGENERATIVE MEDICINE

Stem cells show a high degree of heterogeneity among donors, tissue sources, and within cell populations. This hinders the use of stem cells for tissue engineering and limits their therapeutic efficacy in regenerative medicine.

Scientific knowledge about this heterogeneity is scarce because most conventional assays measure stem cell properties in bulk and, as a consequence, cannot detect inter-cell variation[5].

In living systems, stem cells exist within a three-dimensional environmental niche formed by the extracellular matrix, surrounding cells, certain concentrations of soluble and immobilized chemical substances, and physical and mechanical factors. This niche plays a major role in regulating stem cell fate, including differentiation, functional capacity, and growth rate [6]. EVORION technology enables analyzing the heterogeneity of stem cells among thousands of cells, examining each stem cell within a precisely defined 3D microenvironment. Cells that exhibit desired traits can be selectively propagated for an enriched population with greater therapeutic efficacy.

 

References:

[1] Therapeutic Implications of Cellular Heterogeneity and Plasticity in Breast Cancer.

Brooks MD, Burness ML, Wicha MS.

Cell Stem Cell. 2015 Sep 3;17(3):260-71. doi: 10.1016/j.stem.2015.08.014. Review.

[2] Cancer metastasis: building a framework.

Gupta GP, Massagué J.

Cell. 2006 Nov 17;127(4):679-95. Review.

[3] Significance of Circulating Tumor Cells Detected by the CellSearch System in Patients with Metastatic Breast Colorectal and Prostate Cancer.

Miller MC, Doyle GV, Terstappen LW.

J Oncol. 2010;2010:617421. doi: 10.1155/2010/617421. Epub 2009 Dec 9.

[4] Circulating tumor cells predict survival in early average-to-high risk breast cancer patients.

Rack B, Schindlbeck C, Jückstock J, Andergassen U, Hepp P, Zwingers T, Friedl TW, Lorenz R, Tesch H, Fasching PA, Fehm T, Schneeweiss A, Lichtenegger W, Beckmann MW, Friese K, Pantel K, Janni W; SUCCESS Study Group.

J Natl Cancer Inst. 2014 May 15;106(5). pii: dju066. doi: 10.1093/jnci/dju066. Erratum in: J Natl Cancer Inst. 2014 Sep;106(9):doi/10.1093/jnci/dju273.

[5] On the origin and impact of mesenchymal stem cell heterogeneity: new insights and emerging tools for single cell analysis.

McLeod CM, Mauck RL.

Eur Cell Mater. 2017 Oct 27;34:217-231. doi: 10.22203/eCM.v034a14.

[6] Role of the extracellular matrix in regulating stem cell fate.

Watt FM, Huck WT.

Nat Rev Mol Cell Biol. 2013 Aug;14(8):467-73. doi: 10.1038/nrm3620. Epub 2013 Jul 10. Review.