Pfizer WorldWide Research and Development (R&D), Pearl River, New York.
Published: May 2020
AI Article Synopsis
Article Abstract
Purpose: Gastrointestinal cancers remain areas of high unmet need despite advances in targeted and immunotherapies. Here, we demonstrate potent, tumor-selective efficacy with PF-07062119, a T-cell engaging CD3 bispecific targeting tumors expressing Guanylyl Cyclase C (GUCY2C), which is expressed widely across colorectal cancer and other gastrointestinal malignancies. In addition, to address immune evasion mechanisms, we explore combinations with immune checkpoint blockade agents and with antiangiogenesis therapy.
Experimental Design: PF-07062119 activity was evaluated in multiple tumor cell lines, and in established subcutaneous and orthotopic human colorectal cancer xenograft tumors with adoptive transfer of human T cells. Efficacy was also evaluated in mouse syngeneic tumors using human CD3ε transgenic mice. IHC and mass cytometry were performed to demonstrate drug biodistribution, recruitment of activated T cells, and to identify markers of immune evasion. Combination studies were performed with anti-PD-1/PD-L1 and anti-VEGF antibodies. Toxicity and pharmacokinetic studies were done in cynomolgus macaque.
Results: We demonstrate that GUCY2C-positive tumors can be targeted with an anti-GUCY2C/anti-CD3ε bispecific, with selective drug biodistribution to tumors. PF-07062119 showed potent T-cell-mediated activity and efficacy in multiple colorectal cancer human xenograft tumor models, including and -mutant tumors, as well as in the immunocompetent mouse syngeneic tumor model. PF-07062119 activity was further enhanced when combined with anti-PD-1/PD-L1 treatment or in combination with antiangiogenic therapy. Toxicity studies in cynomolgus indicated a monitorable and manageable toxicity profile.
Conclusions: These data highlight the potential for PF-07062119 to demonstrate efficacy and improve patient outcomes in colorectal cancer and other gastrointestinal malignancies.
Purpose: The association between statin use and cancer survival has been investigated in previous studies with conflicting findings. This study aimed to assess the association between statin use following cancer diagnosis and survival in six common cancers using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database.
Methods: Individuals aged ≥ 66 years diagnosed with prostate cancer, colorectal cancer, lung cancer, bladder cancer, pancreatic cancer, or non-Hodgkin lymphoma (NHL) from 2008 through 2017 were identified.
Extensive research is needed to examine the association between cardiovascular disease (CVD) and cancer. The observational study is based on data collected from the 2005-2018 National Health and Nutrition Examination Survey (NHANES). To assess the connection between CVDs and cancer, we used a weighted multivariable logistic regression analysis with as many confounding factors as feasible included in the model.
State key laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China; State Key Laboratory of Dampness Syndrome, The Second Affiliated Hospital Guangzhou University of Chinese Medicine, Dade Road 111, Guangzhou, China. Electronic address:
ASPN-1, a novel glucan with a molecular weight of 33.31 kDa, was purified from Acanthopanax senticosus stems, characterized in structure, and evaluated for antitumor potential. The analysis of the structure of ASPN-1 revealed that it consisted of a backbone constructed from →4)-α-D-Glcp-(1 → glucosyls, branched at the O-3 position by an α-D-Glcp-(1 → residue and at the O-6 positions with α-D-Glcp-(1 → 6)-α-D-Glcp-(1 → and/or α-D-Glcp-(1 → residues.
