A Comparative Evaluation of Immunotherapy Responses in Murine Colon Carcinoma

Introduction and Background With the drive in oncology to develop molecules targeting the immune system, there is a need for reliable and well-characterized preclinical models. The focus of immuno-oncology drug development has shifted to combination strategies with approved immunotherapies, immunometabolism targets, and costimulatory molecules. To better understand the utility of […]

ID8 Syngeneic Ovarian Cancer Model Response to Checkpoint Inhibitors

Fig. 2: Intraperitoneal ID8-luc: Representative BLI Images Over Time   Body Weight Changes with Use of Checkpoint Inhibitors Treatment with checkpoint inhibitors was not associated with any significant body weight change relative to control animals (Figure 3A). The median survival of animals treated with anti-mCTLA-4 was comparable to control animals […]

Strategies for Selecting the Right Immuno-Oncology Tumor Model

Tumor Placement The choice of tumor placement has long been important in preclinical development. The classical subcutaneous tumor implant on the flank of the mouse allows for ease of measurement by caliper, is minimally invasive allowing for large studies, and tumor growth kinetics on the flank is generally reproducible. However, […]

ID8: A Syngeneic Mouse Model for Testing Ovarian Cancer Immunotherapies

Ovarian cancer is an unmet medical need and particularly lethal because it is often detected only when disease is quite advanced. In 2017, approximately 22,440 women will be diagnosed with ovarian cancer in the United States, and approximately 14,080 deaths will occur. Combination platinum and anti-mitotic taxane based chemotherapy is the standard of care in […]

Advancements and Challenges of Imaging in the Immuno-Oncology Space

Immunotherapy agents (IO) are increasingly being used to treat solid tumors due to their dramatic effects on tumor response. However, the assessment of tumor response is not always straightforward given their unique mechanisms of action which include enhancing immune cell infiltration and activation in tumors. Current standard imaging techniques such as fluorinated deoxy-glucose (18F-FDG) PET […]

A20: Modeling B Cell Lymphoma in Mice

Lymphomas represent a highly heterogenous set of lymphoid cell malignancies. They can originate from either B or T cells, but B cell-derived lymphomas, specifically non-Hodgkin lymphoma (NHL), are the most prevalent. Lymphomas can be diagnosed in children and adolescents, but incidence of lymphoma increases significantly with age, the median age of diagnosis being 67 years. […]

Pan02 – Pancreatic Ductal Adenocarcinoma Model Characterized for Immuno-oncology Applications

Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent form of pancreatic cancer representing about 95% of all cases. In 2017, approximately 50,987 people will be diagnosed with PDAC in the United States, and approximately 40,936 patient deaths will occur, making PDAC one of the most lethal forms of cancer. Combination anti-metabolite and anti-mitotic taxane based […]

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 […]

Characterization of Proliferation in Multiple Lymphocyte Subsets in the CT26 Murine Colon Carcinoma Model by Multi-color Flow Cytometry

“Characterization of Proliferation in Multiple Lymphocyte Subsets in the CT26 Murine Colon Carcinoma Model by Multi-color Flow Cytometry” Introduction and Background: The efficacy of immune-modulating anti-cancer therapeutic antibodies that have been FDA-approved in recent years, such as anti-CTLA-4, anti-PD-1, and anti-PD-L1, has altered the paradigm of cancer treatment. Subsequently, the […]

C1498: A Murine Model for Acute Myelogenous Leukemia (AML)

Survival (morbidity/mortality) kinetics (Figure 2A) show a median survival of approximately 23 days; although, the mice show no body weight loss during the course of disease progression (Figure 2B). Survival Kinetics and Body Weight Change Fig. 2: Survival kinetics (A) and body weight change (B) of C57BL/6 mice with disseminated […]

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 […]

GL261-luc: A Model for Immunotherapy and Radiation Therapy

In addition to bioluminescence, Covance has a host of other imaging technologies, including PET, MRI, SPECT, CT, and fluorescence modalities, to further interrogate parameters related to GBM such as tumor volume, vascular perfusion/permeability, metabolic activity, and edema. Covance also has comprehensive In Vitro Services including flow cytometry to best evaluate […]

4T1-luc2: An Orthotopic Mammary Cancer Model to Support Novel Immuno-Oncology Drug Discovery

Breast cancer is the second most deadly malignancy after lung cancer in woman in the United States, with an estimated 246,000 new cases and 40,450 deaths expected in 2016. Many treatment options for breast cancer exist including surgery, radiotherapy, anti-estrogen therapy, targeted therapies (e.g., trastuzumab), and chemotherapy. Despite these therapeutic advances, metastatic disease remains a […]

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 Covance we have been utilizing preclinical imaging technologies for over a […]

5TGM1-luc – A Syngeneic Murine Model for Multiple Myeloma

The 5TGM1 multiple myeloma model arose spontaneously in aging C57BL/KaLwRij mice, and was propagated via serial passage in syngeneic mice prior to establishment of a cell line. Covance’s 5TGM1 line has been luciferase-enabled to permit monitoring of growth in orthotopic sites such as the bone marrow by bioluminescent imaging (BLI). […]

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 […]

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 […]