Oncology and Immuno-Oncology INSIGHTS

On Monday, October 1, 2018 the Nobel Committee announced the recipients of this year's Nobel Prize in Physiology or Medicine. The two Nobel laureates were James P. Allison — a professor and immunologist from MD Anderson Cancer Center — and Tasuku Honjo — an immunologist from Kyoto University. Both researchers split the prize evenly for their pioneering discoveries relating to "cancer therapy inhibition of negative immune regulation."...  Read More

October is National Breast Cancer Awareness Month. There is a lot to be excited about this year as mortality rates continue to drop for major cancer types, including breast cancer. Between 1989 and 2015 deaths from breast cancer specifically declined 39%, a decline American Cancer Society attributes to "improvements in early detection." There's still work to be done, however. An estimated 270,000 new cases of breast cancer...  Read More

Alterations in the microbiome have an acknowledged role in cancer pathology1,2. Earlier this year, however, researchers at New York University published a manuscript3 connecting the pancreatic microbiome to cancer progression. In this report, Pushalkar et al. demonstrate that the endogenous microbiome of the pancreas can drive immunosuppressive conditions in humans and mice, which creates a pro-tumorigenic state. Treatment regimens that include modulating the microbiome show promise for...  Read More

Breast cancer xenograft models are often treated with supplemental estrogen, but this can induce a range of adverse effects on immunodeficient mouse models including impaired urinary tract function and skin problems. Failure to control for these strain-dependent effects can seriously impact the reproducibility of preclinical research — or lead to early termination of your experiment due to their severity. In a recent webinar, Pharmatest — a contract...  Read More

Humanized mice engrafted with human peripheral blood mononuclear cells (PBMCs) have become the preclinical workhorses for evaluating bispecific antibodies and other multi-specific, T cell-engaging cancer immunotherapies. PBMC-engrafted models, such as huPBMC-NOG are favored for their relative speed, versatility, affordability, and high level of translational relevance. Key to the effective application of PBMC-engrafted models is an understanding of their strengths and limitations. This article will highlight these strengths...  Read More

The fight against cancer has recently improved by enlisting the patient's immune system to battle tumor cells. Administering checkpoint inhibitors, for example, can stop molecules such as PD-1 from interfering with T cell activity and allow T cells to attack cancer cells. Keytruda® (Merck) and Opdivo® (BMS) are two well-known checkpoint inhibitors that have improved treatment of certain cancer types. Checkpoint inhibitors work indirectly. CAR T cells...  Read More

Favored for their relative speed, versatility, and translational relevance, humanized mice engrafted with human peripheral blood mononuclear cells (PBMCs) are the go-to preclinical models for evaluating T-cell-dependent immunotherapies. However, lacking important human cytokine signals, huPBMC-NOG and other PBMC models fail to support engraftment of important human immune cell subtypes, such as natural killer (NK) cells. This limits their utility for many studies. Recent work from Taconic Biosciences...  Read More

The preclinical research community responded enthusiastically to Dr. Paul Volden's recent webinar, Next Generation Humanized Mice in Immuno-Oncology, the second webinar in a two-part series on humanized mice for preclinical immuno-oncology (IO). Several questions had to be cut from the presentation for time and are presented here, in full. Preclinical Immuno-Oncology Q&A Dr. Paul Volden (PV): The number of cells obtained from individual hematopoietic stem cell (HSC)...  Read More

Dr. Paul Volden recently presented a webinar on humanized mice in preclinical immuno-oncology research. Many of the questions you submitted to his Q&A session went unanswered due to time constraints, so here's the full Q&A. General Immuno-Oncology Questions Dr. Paul Volden (PV): I would not recommend commercially available humanized models for most cancer vaccine studies. To get sufficient vaccine response, you need interaction between antigen presenting cells...  Read More

Humanized mice are invaluable tools for studying the function of the human immune system in an in vivo context, with applications for studying infectious disease, immuno-oncology, and immunology. Recently, Ryoji Ito and colleagues at the Central Institute for Experimental Animals in Japan demonstrated their efficacy in assessing the safety of chemotherapeutic drug candidates1. Humanized Mice and Myelotoxicity Testing Myelotoxicity is a common treatment-related adverse effect for antineoplastic...  Read More