Resources and Tools for contract research
Resources and tools available at Department of Medical Oncology, Erasmus MC for pre-clinical and early clinical studies on drugs.
Pre-clinical studies:
- Large collection of well characterized cell lines of many tumor types, among which breast cancer, sarcoma, and melanoma cell lines. For example, the collection of 41 breast cancer cell lines is extremely well characterized (i.e. screened for all common oncogenic mutations and profiled on gene expression arrays), and was found to have retained most molecular characteristics that are typical for clinical breast cancers. The collection consists of 20 luminal cell lines, 15 basal and normal-like cell lines and one unclassified cell line, all together including 13 ERBB2-overexpressing cell lines and 17 triple-negative cell lines.
- MLI and II tissue culture facilities for in vitro studies, including drug sensitivity screening, invasion and migration assays, and various luciferase-based reporter assays.
- Stable or transient silencing or over expression of target genes (including those coding for micro RNAs). For stable introduction, we use third generation lentiviral vectors; for transient manipulation regular mammalian expression vectors or siRNA molecules are used.
- Experimental DMI and II animal facilities to study tumor cell line xenografts in mice and rats, including orthotopic BN-472 breast cancer (metastasizes to lungs and lymph nodes), transplantable EnDA endometrial cancer (metastasizes to lungs and lymph nodes), transplantable CC-531 colon carcinoma (metastasizes to lungs and lymph nodes), transplantable CA-20948 pancreatic adenocarcinoma (metastasizes to liver and lymph nodes), and a panel of transplantable mouse and human melanoma cell lines (with varying capacities to metastasize to lungs). In addition, we have available mice with spontaneous melanoma, and mice transgenic for human transplantation antigens (Major Histocompatibility Class I and II) to study T cell therapy towards human antigens in an immune competent setting.
- Large tumor bank of human breast cancer samples that can be screened for presence of specific drug targets by RT-PCR or immunohistochemistry.
- Drugs suitable to be combined with immune therapy could be tested in available in vitro and in vivo immune therapy models. We developed a panel of immunoreceptors (antibodies as well as T cell receptors) to genetically engineer immune cells, such as T cells, and to test immune therapy directed against tumors that express various antigens.
- Our laboratory is equipped to do all standard molecular and cell biological techniques including multicolor flowcytometry, PCR, real time RT-PCR, western blotting, IHC, ELISA, Mass spectrometry, HTS sequencing and various types of micro array analysis.
Clinical studies:
- GLP-approved laboratorium of pharmacology (determination of drug levels and their metabolites in serum/plasma and if possible in healthy and tumor tissue by microdialysis).
- GMP units and expertise to conduct immuno(gene)therapy trials.
- Multicolor (up to 6 colors) flow cytometry for enumeration of lymphocyte subsets in blood, immune monitoring (detection of antigen-specific immune using class I and II HLA multimers), assessment of apoptosis in blood leukocyte subsets, and detection of rare events in CCKL-accredited unit.
- Determination of antigen-specific immune responses using one or more of the following functional assays: (i) simultaneous detection of multiple intracellular cytokines and activation markers with or without stimulation; (ii) lymphocyte proliferation assays; and (iii) cell-mediated cytotoxicity assays.
- Enumeration, isolation and characterisation of circulating tumor cells (CTCs) and circulating endothelial cells (CECs) using CellSearch instrument and additional techniques.
- Determination of single and multiple soluble serum factors (e.g. angiogenic factors, growth factors) by ELISA and multi-plex technology.
- Determination of expression and activation state of numerous factors (e.g., growth factor receptors and down-stream signalling intermediates) in malignant and benign tissue such as skin, buccal mucosa, and peripheral blood mononuclear cells (PBMCs).
For further information, please see the several research groups at our website.