The State of Modeling Preclinical Immuno-Oncology Pharmacology

The field of cancer immunology or immuno-oncology (I/O) dates back to the 1890’s with efforts by William Coley to treat malignancies by infection with certain bacterial strains.1 Fast forward 120 years, and we have observed the clinical success of multiple checkpoint inhibitor antibodies against cancer specific T cell negative regulatory pathways in multiple cancer types.2 […]

Phospho-Flow Cytometry for the Screening of Intracellular Signaling Events in Cancer Cells and Immune Cells

Pre-clinical research on the development of small molecule inhibitors that block the activity of disease-associated kinases continues to be a major focus of cancer therapy. Therefore, robust platforms that can quantify the phosphorylation state of these kinases are valuable to drug development efforts. Using the MV-4-11 acute myeloid leukemia (AML) model, this update describes new […]

Image Analysis at MI Bioresearch

Analysis of biomedical imaging data is no less a task than the image acquisition itself. Due to the complex nature of such data and variability across different subjects, information extraction has largely remained a time-consuming process. Vendors of imaging instruments and specialty software offer a variety of tools; however, a user still needs to work […]

Preclinical Success to Clinical Failure: Do We Have a Model Problem or an Endpoint Problem?

As the AACR (American Association for Cancer Research) Annual Meeting is fast approaching, many industry and academic scientists are busy preparing talks and posters for what they hope will be the next new wave in cancer therapy or the next “new and improved” preclinical model. However, while these may be long shots, it’s the scientific […]

Use of Luminex® Technology to Quantify Biomarkers and Provide Agent Efficacy

In recent years many researchers have focused on the analysis of circulating soluble cancer biomarkers as an indicator of the host immune response to oncogenesis.1,2,3 Multiple biomarkers can be quantified in order to fully characterize changes in homeostasis brought on by tumor growth and metastasis. The ability to multiplex tumor-type specific antigens and general immune […]

Measuring Extracellular pH Within Tumors Using CEST MRI

pH is one of the key microenvironmental factors in the development of tumors. Tumor cells are often viewed as high lactate and H+ producers.1 Extracellular acidosis represents a threat to cell survival by modifying the intracellular pH (pHi), wherein a 0.1 pHi variation can disrupt multiple biological functions.2 Measurements of tumor extracellular pH (pHe) may […]

Immune Profile of the Neuro-2a Mouse Neuroblastoma Model by Flow Cytometry

Neuroblastoma is an extracranial tumor that arises from neural crest-derived progenitor cells. It is the most prevalent solid tumor in childhood and the most common tumor in infants less than one year of age. With up to 800 new cases diagnosed each year, in spite of aggressive multi-modal therapeutic approaches, the 5-year survival rate in […]

Longitudinal Evaluation of Orthotopic Lung Tumors With Imaging

Clinical imaging technologies have been vital for detecting and following disease progression/regression for many years, as examples, Computed Tomography (CT) can measure tumor volume over time and Positron Emission Tomography (PET) can measure metabolic activity within the tumors. At MI Bioresearch we have been utilizing preclinical imaging technologies for over […]

Leveraging the Clinical Power of MRI in Preclinical Liver Tumor Imaging

The liver is an ideal organ for magnetic resonance imaging (MRI) due to its size, plus the inherent contrast it enables compared to other tissues and lesions; this results from the high iron content which acts as a natural MRI contrast agent. For such reasons, liver tumor MRI is a major area of clinical and […]

Flow Cytometry Based Functional Assays Essential for Characterizing Biological Significance

NK Cell Stimulation: Splenocytes or dissociated tumors are cultured with IL-12 and IL-18, treated to prevent excretion of produced cytokines. Expression of markers including IFN-γ are quantified to identify activated NK cells within the total NK cell population. B-cell Stimulation: Splenocytes or dissociated tumors are cultured with IgM and expression […]

Approaches for Preclinical Evaluation of Ovarian Cancer

As many patients with ovarian cancer develop peritoneal ascites, one standard preclinical method is to deliver these cell lines intraperitoneally (IP) to mimic this disease state. With our luciferase expressing lines we are able to track and monitor disease establishment and progression with BLI and report out quantitative measurements of […]

In-Depth Myeloid Cell Characterization in the Murine Syngeneic CT.26 Colon Carcinoma Model by 10-Color Flow Cytometry

The efficacy of immune-modulating anti-cancer therapeutic antibodies that have been FDA-approved in recent years, such as anti-CTLA-4 and anti-PD-1, has driven growing interest in methods that provide a mechanistic understanding of drug function. Development of new mono- and combination therapies with immune-modulatory effects requires more powerful immunophenotyping techniques capable of in depth cell characterization. During […]

Evaluation of the Immune Response Following Treatment with Anti-CTLA-4 Antibody, Radiation Therapy, or the Combination in Murine Model of Breast Cancer

Breast cancers are considered poorly immunogenic tumors, however, several approaches utilizing immunotherapies are being undertaken in the clinic to evaluate their potential for improving outcomes. Radiation therapy (RT) is a highly utilized clinical treatment modality in breast cancer. Radiation is known to modify the tumor microenvironment, induce cytokines and chemokines, and has been shown to […]

Access the Power of Focal Beam Radiation Using Xstrahl’s SARRP

Xstrahl’s SARRP (Small Animal Radiation Research Platform), incorporates CT imaging with precise radiation delivery to enable researchers to pinpoint an exact anatomical target. This small animal irradiator can then deliver single or multiple beams of radiation to the target with the upmost accuracy, matching the clinical techniques used in oncology […]

PET Quantification of Receptor Occupancy

The use of PET imaging to detect and quantify receptor occupancy (RO) has become a translational standard in CNS discovery and clinical trials. For example, 18F radiolabeling of targeted small molecules enables a PET tracer-based PD biomarker. The tracer can be used for dynamic, non-invasive quantification of percentage RO. For relevant targets, rodent models can […]

Quantify T Cell Biodistribution Non-Invasively in Animal and Human Subjects

MI Bioresearch (MI) is looking for expressions of interest from companies involved in CAR-T and T Cell Receptor therapies, regarding non-invasive cell tracking in vivo.  MI is using a validated MRI platform that can be used to label T cells and detect/track cells in rodents.1  This strategy can also be implemented in NHP studies and clinical […]

Get Glowing Results From Your Cell Lines – With Luciferase

Since different cell types use different promoters to express genes, a variety of promoters including EF1 alpha, CMV, UbC, and MSCV can be used. Also, for high-efficiency gene delivery, the pseudotype of the virus can be modified to VSV-G or MLV. If you are interested in luc-enabling your cell lines, contact […]

Old Methods for a New Therapy — Imaging Gene Delivery

The promise of gene based therapies is stronger than ever.  Testament to this is the strides being taken in several areas; including mRNA based delivery and RNA interference.1 These successes are driving “new” applications for an “old” in vivo imaging assay, bioluminescence imaging (BLI).  BLI is based on detection of a reporter gene/protein (traditionally firefly […]

Precision Imaging of Antibody Biodistribution in vivo With Zirconium-89 PET

Zirconium-89 (89Zr) has revolutionized discovery and translation of Ab (and Ab fragment) therapeutics via PET biodistribution imaging.  With standard, straightforward labeling chemistry, 89Zr provides unprecedented specificity and sensitivity of PET Ab detection (to pM levels).  At MI Bioresearch we use 89Zr PET as a platform assay for in vivo quantification of: Ab targeting precision Off […]

Quantifying in vivo Biodistribution and Kinetics of Your Biologic or Nanomaterial

With the ability to provide non-invasive, three dimensional, longitudinal, and quantitative data—PET, SPECT, and fluorescence imaging (FMT) enable translational imaging of: Biodistribution Targeting Kinetics Clearance Pathways In vivo biodistribution imaging applications are now critical assays for biologics characterization for discovery screening, lead candidate selection/optimization and safety. At MI Bioresearch (MI) we combine highly sensitive PET, SPECT, […]