Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of cells that accumulate in tumor-bearing subjects and which strongly inhibit anti-cancer immune responses. To study the biology of MDSC in colorectal cancer (CRC), we cultured bone marrow cells in conditioned medium from CT26 cells, which are genetically modified to secrete high levels of granulocyte-macrophage colony-stimu...

The structure and T cell stimulatory effects of the recently discovered cytokine IL-23 are similar to, but distinct from, those of IL-12. Although the antitumor activities of IL-12 are well characterized, the effect of IL-23 on tumor growth is not known. In this study, murine CT26 colon adenocarcinoma and B16F1 melanoma cells were engineered using retroviral vectors to release single-chain IL-2...

Malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) is a predicted oncoprotein that demonstrates tumorigenic activity in vivo; however, the mechanisms involved are unknown. Macrophages are divided into the pro-inflammatory M1 and anti-inflammatory/protumoral M2 subtypes. Tumor cells can induce M2 polarization of tumor-associated macrophages (TAMs) to promote metastasis; but the underly...

There is accumulating evidence that CD4(+) T cell responses are important in antitumor immunity. Accordingly, we generated CD4(+) T cells against the murine CT26 colon cancer. Three of three independent CT26-specific CD4(+) hybridomas were found to recognize the high m.w. precursor of the env gene product gp90. The CD4(+) response was completely tumor specific in that the same glycoprotein expr...

Cancers can be addicted to continued and relatively high expression of nuclear oncoproteins. This is evident in colorectal cancer (CRC) where the oncoprotein and transcription factor MYB is over expressed and essential to continued proliferation and tumour cell survival. Historically, targeting transcription factors in the context of cancer has been very challenging. Nevertheless, we formulated...

BACKGROUND T-cell checkpoint blockade and MEK inhibitor combinations are under clinical investigation. Despite progress elucidating the immuno-modulatory effects of MEK inhibitors as standalone therapies, the impact of MEK inhibition on the activity of T-cell checkpoint inhibitors remains incompletely understood. Here we sought to characterize the combined effects of MEK inhibition and anti-CTL...

Background Immunotherapy based on anti CTLA-4 (αCTLA-4) and PD1 (αPD1) is being tested in combination with different therapeutic approaches including other immunotherapy such as neoantigen cancer vaccines (NCV). Here we explored, two murine models, combinations of αCTLA-4 and/or αPD1 a plasmid DNA vaccine expressing neoantigens delivered by electroporation (EP). Materials Methods To evaluate th...

objective: nucleostemin (ns) is a recently identified gene that is expressed mainly in the nucleoli of neuronal, embryonic and mesenchymal stem cells which plays a role in their self renewal. over expression of this gene has been reported in several cancer cell lines tumoral tissues including gastric, hepatic and prostate cancer. in this study, we investigated the effects of suppression of this...

background : the development of chemoresistance represents a major obstacle in the successful treatment of cancers such as non-hodgkin’s lymphoma (nhl). with the recognition of important roles for both p53 and its more recently described paralog p73 in mediating the activity of anti-cancer drugs, there has been increasing recognition that cellular resistance to anthracyclines could and does a...

Beta-glucuronidase (βG) is a potential biomarker for cancer diagnosis and prodrug therapy. The ability to image βG activity in patients would assist in personalized glucuronide prodrug cancer therapy. However, whole-body imaging of βG activity for medical usage is not yet available. Here, we developed a radioactive βG activity-based trapping probe for positron emission tomography (PET). We gene...