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 […]

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 […]

Sensitivity of Syngeneic Tumor Models to Focal Radiation

Introduction and Background Use of image-guided focal irradiation is a mainstay of human cancer treatment. Image guidance allows for highly conformal treatment plans that minimize normal tissue toxicity and systemic response. With the advent of image-guided small animal irradiators such as the Small Animal Radiation Research Platform (SARRP; Xstrahl Inc., […]

Preclinical Models of Multiple Myeloma

Introduction and Background Multiple myeloma is a clonal B cell malignancy characterized by the accumulation of terminally differentiated, antibody-producing plasma cells in the bone marrow that is invasive and drug resistant. Patients are generally asymptomatic until very late state disease. There are few preclinical models that recapitulate human disease. In […]

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 […]