Combined Focal Radiation and Anti-mCTLA-4 Antibody Therapy Modulates Myeloid Subset Phospho-STAT3 Levels in the 4T1 Tumor Microenvironment, and Results in Tumor Growth Inhibition

Introduction and Background Signaling through signal transducer and activator of transcription factor 3 (STAT3) in myeloid subsets triggers gene expression that has direct and indirect suppressive effects on several immune subsets. Selective targeting of STAT3 in myeloid cells has become an attractive therapeutic approach as it can prevent adverse effects […]

An Introduction to Dendritic Cell Biology and Analysis Using Syngeneic Immuno-Oncology Models

Productive immunotherapy driven anti-tumor responses rely on the activation of T cells that target tumor-associated antigens (TAA). The dendritic cell (DC) plays an essential role in the activation of T cell antigen-specific responses, which occurs naturally in the context of infection. However, this same process supports tumor immune surveillance as well as active anti-tumor responses. […]

Subcutaneous and Systemic Preclinical Modeling of A20 Murine B Cell Lymphoma

Lymphomas represent a set of lymphoid cell malignancies that can range from indolent to aggressive. B cell-derived lymphomas, specifically non-Hodgkin lymphoma (NHL), are the most prevalent, but this disease can also originate from T cells. In 2018, an estimated 74,680 new cases of NHL in the United States will be diagnosed, and 19,910 patient deaths […]

Hepa 1-6: A Murine Model of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is an aggressive malignancy which has gradually increased in incidence to affect one million people worldwide and is currently the third leading cause of cancer related deaths in the world.[1,2] The prevalence of HCC is highest in Asia and Africa due to high endemicity of hepatitis B and C viruses which strongly […]

Emerging Immuno-Oncology Therapies: Life After Checkpoint Inhibitors

The clinical approval of biological therapeutics inhibiting CTLA-4 (ipilimumab), PD-1 (nivolumab, pembrolizumab) and PD-L1 (atezolizumab, avelumab, durvalumab) has ushered in a revolution in the field of cancer immunotherapy. Thus far, the approvals have occurred in a small number of cancer histotypes including melanoma, non-small cell lung cancer and urothelial cancers, but over 2000 active clinical […]

E0771 Syngeneic Breast Cancer Model

Triple negative breast cancer (TNBC) is a complex and aggressive subtype of breast cancer lacking estrogen receptor, progesterone receptor, and HER2 amplifications; making it difficult to target therapeutically. Consequently, there’s a constant demand for better treatment options for TNBC. To help address the need for TNBC models, we highlighted the EMT6 model last month and […]

Flow Cytometry-Based Tools to Enrich Your Preclinical Immuno-Oncology Research

Overview: Flow cytometry provides a highly adaptable and quantitative method for investigating both the cellular distribution and intracellular changes that occur in tumors and peripheral lymphoid organs in response to therapy. As clinical successes with cancer immunotherapy accumulate, preclinical immuno-oncology research depends on greater mechanistic understanding of novel therapeutic strategies. […]

Immuno-Metabolism Impacts on T Cell Populations

We are all familiar with cellular metabolism and how the production of ATP (cell energy) is critical for cell development, proliferation, and survival. Understanding the impact of immuno-metabolism and how this area can enhance the ever-evolving immuno-oncology research is a new and exciting field. Since the cells of the immune system are a fundamental component […]

EMT-6 Syngeneic Breast Tumor Model – A Powerful Tool for Immuno-Oncology Studies

Breast cancer is the most common cancer among women in the United States and is the fourth leading cause of cancer death. In 2017, an estimated 252,710 new cases were diagnosed (15% of all new cancers) and 40,610 patient deaths occurred. Early detection initiatives together with improved treatment options have resulted in increases in the […]

High-Throughput Analysis of MAPK and JAK-STAT Signaling in CT26 Tumors Using a Combination of Immunophenotyping and Phospho-Flow Cytometry

Introduction and Background The development of robust platforms that enable phospho-protein-based analysis of cell signaling in the tumor microenvironment is pivotal for small molecule drug development. Currently lacking are reliable applications that can simultaneously measure multiple phospho-proteins in both tumor cells and immune cells ex vivo. This can be crucial […]

Evaluation of Immunomodulatory Agents in Classically Immunologically “Cold” Cancers Using Syngeneic Mouse Models of Breast and Ovarian Cancer

Introduction and Background T cell checkpoint inhibitors have demonstrated significant clinical benefit in immunologically “hot” cancer types like melanoma, kidney, bladder and lung cancers. “Hot” tumors are characterized by a significant CD8+ T cell infiltrate and high neoantigen burden. Breast cancer is regarded as an immunologically “cold” cancer, often with […]

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 […]