Immune cell infiltration pattern in non-small cell lung cancer PDX models is a model immanent feature and correlates with a distinct molecular and phenotypic make-up.

Background: The field of cancer immunology is rapidly moving towards innovative therapeutic strategies, resulting in the need for robust and predictive preclinical platforms reflecting the immunological response to cancer. Well characterized preclinical models are essential for the development of predictive biomarkers in the oncology as well as the immune-oncology space. In the current study, gold standard preclinical models are being refined and combined with novel image analysis tools to meet those requirements.

Author Correction: Evaluation of molecular subtypes and clonal selection during establishment of patient-derived tumor xenografts from gastric adenocarcinoma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Evaluation of molecular subtypes and clonal selection during establishment of patient-derived tumor xenografts from gastric adenocarcinoma.

Patient-derived xenografts (PDX) have emerged as an important translational research tool for understanding tumor biology and enabling drug efficacy testing. They are established by transfer of patient tumor into immune compromised mice with the intent of using them as Avatars; operating under the assumption that they closely resemble patient tumors. In this study, we established 27 PDX from 100 resected gastric cancers and studied their fidelity in histological and molecular subtypes.

Induction of Acquired Resistance towards EGFR Inhibitor Gefitinib in a Patient-Derived Xenograft Model of Non-Small Cell Lung Cancer and Subsequent Molecular Characterization.

In up to 30% of non-small cell lung cancer (NSCLC) patients, the oncogenic driver of tumor growth is a constitutively activated epidermal growth factor receptor (EGFR). Although these patients gain great benefit from treatment with EGFR tyrosine kinase inhibitors, the development of resistance is inevitable. To model the emergence of drug resistance, an EGFR-driven, patient-derived xenograft (PDX) NSCLC model was treated continuously with Gefitinib in vivo.

Patient derived renal cell carcinoma xenografts exhibit distinct sensitivity patterns in response to antiangiogenic therapy and constitute a suitable tool for biomarker development.

Systemic treatment is necessary for one third of patients with renal cell carcinoma. No valid biomarker is currently available to tailor personalized therapy. In this study we established a representative panel of patient derived xenograft (PDX) mouse models from patients with renal cell carcinomas and determined serum levels of high mobility group B1 (HMGB1) protein under treatment with sunitinib, pazopanib, sorafenib, axitinib, temsirolimus and bevacizumab.

Depletion of Mouse Cells from Human Tumor Xenografts Significantly Improves Downstream Analysis of Target Cells.

The use of in vitro cell line models for cancer research has been a useful tool. However, it has been shown that these models fail to reliably mimic patient tumors in different assays(1). Human tumor xenografts represent the gold standard with respect to tumor biology, drug discovery, and metastasis research (2-4).

Effective Eradication of Glioblastoma Stem Cells by Local Application of an AC133/CD133-Specific T-cell-Engaging Antibody and CD8 T Cells.

Cancer stem cells (CSC) drive tumorigenesis and contribute to genotoxic therapy resistance, diffuse infiltrative invasion, and immunosuppression, which are key factors for the incurability of glioblastoma multiforme (GBM). The AC133 epitope of CD133 is an important CSC marker for GBM and other tumor entities. Here, we report the development and preclinical evaluation of a recombinant AC133×CD3 bispecific antibody (bsAb) that redirects human polyclonal T cells to AC133(+) GBM stem cells (GBM-SC), inducing their strong targeted lysis.

Noninvasive positron emission tomography and fluorescence imaging of CD133+ tumor stem cells.

A technology that visualizes tumor stem cells with clinically relevant tracers could have a broad impact on cancer diagnosis and treatment. The AC133 epitope of CD133 currently is one of the best-characterized tumor stem cell markers for many intra- and extracranial tumor entities. Here we demonstrate the successful noninvasive detection of AC133(+) tumor stem cells by PET and near-infrared fluorescence molecular tomography in subcutaneous and orthotopic glioma xenografts using antibody-based tracers.

Intratibial injection of human multiple myeloma cells in NOD/SCID IL-2Rγ(null) mice mimics human myeloma and serves as a valuable tool for the development of anticancer strategies.

Background: We systematically analyzed multiple myeloma (MM) cell lines and patient bone marrow cells for their engraftment capacity in immunodeficient mice and validated the response of the resulting xenografts to antimyeloma agents.

Design And Methods: Using flow cytometry and near infrared fluorescence in-vivo-imaging, growth kinetics of MM cell lines L363 and RPMI8226 and patient bone marrow cells were investigated with use of a murine subcutaneous bone implant, intratibial and intravenous approach in NOD/SCID, NOD/SCID treated with CD122 antibody and NOD/SCID IL-2Rγ(null) mice (NSG).

Results: Myeloma growth was significantly increased in the absence of natural killer cell activity (NSG or αCD122-treated NOD/SCID).

Anti-tumor activity of a B-cell receptor-targeted peptide in a novel disseminated lymphoma xenograft model.

Receptor-targeted therapies have become standard in the treatment of various lymphomas. In view of its unparalleled specificity for the malignant B-cell clone, the B-cell receptor (BCR) on B cell lymphoma cells is a potential therapeutic target. We have used two BCR epitope mimicking peptides binding to the Burkitt's lymphoma cell lines CA46 and SUP-B8.