Evaluating the Genetic Damage Caused by Cancer Treatments

LabRoots | November 18, 2019

Throughout our lives, our bodies have to constantly replenish old cells with new ones; a cell can give rise to two new ones and the genome has to be copied and divided evenly between the two new cells every time. Our cells are also exposed to a wide variety of detrimental environmental influences, like toxins or UV rays. Inevitably, errors can arise in the genome, and while some are harmless, others can lead to uncontrolled cell growth - cancerous tumors. During cancer treatment, therapeutics take aim at tumor cells, and some target their DNA. While these treatments are meant to impact only cancerous cells, they can also cause collateral damage to healthy cells. In new work reported in Nature Genetics, a team of researchers has assessed how six widely used cancer therapies affect the genome. Five of these treatments are chemotherapies (platinum-based drugs and capecitabine) and one is radiotherapy, which uses radiation. "It is important to remember that chemotherapies are highly efficient for the treatment of cancer," noted the first author of the study Oriol Pich, a graduate student at the Institute for Research in Biomedicine (IRB Barcelona). "But long-term side effects have also been reported in some patients. Studying the DNA mutations that occur in cells as a result of chemotherapies is the first step towards understanding the relationship between these mutations and the long-term side effects of these treatments."

Spotlight

In keeping with its history of manufacturing innovation and excellence, Amgen is leading the way in the development
and use of manufacturing technologies that will set the standard for the future.

Spotlight

In keeping with its history of manufacturing innovation and excellence, Amgen is leading the way in the development
and use of manufacturing technologies that will set the standard for the future.

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DIAGNOSTICS

Phenomix Sciences Announces First Obesity Biobanking Registry and Outcomes Study for Precision Nutrition and Obesity

Phenomix Sciences | May 27, 2022

Phenomix Sciences (Phenomix), a precision biotechnology company bringing data intelligence to the treatment of obesity, announces today the launch of its biobanking registry and outcome study. The registry will study variability in obesity by looking at patients' DNA, metabolomics, hormones, patient behavior, assessments, and treatment outcomes. The data collected will supplement the 20 billion unique data points that make up the Phenomix Sciences Obesity Platform. Mayo Clinic is the first to enroll in the registry with its Rochester site set to contribute patient outcomes from 2,000 patients undergoing treatment for obesity to its biobank. The biobanking registry is a critical milestone in Phenomix's mission to conquer obesity by creating unprecedented access to its clinical and molecular information throughout all stages and phenotypes of the disease. Outcomes data generated from the biobanks across the registry will supplement Phenomix's database of biological and clinical data matched to the four obesity phenotypes. Insights generated from the database are being used to develop more predictive tests to identify the right intervention for each patient with obesity. This will allow for a better understanding of variability in patient outcomes when undergoing obesity treatments. Despite the justifiable excitement about new weight management products such as semaglutide and tirzepatide, several clinical studies from Phenomix's founders indicate that patient response varies with underlying phenotype. Thus, for many patients, it will open the door to the most effective and appropriate intervention for their unique phenotype. A growing body of evidence indicates that obesity is not a single disease with a single treatment type, but a constellation of diseases. Obesity's roots lie in individual DNA; however, evidence suggests there is a complicated web connecting obesity to age, race, and gender, education, and socioeconomic status. Understanding a person's obesity phenotype — the combination of genes with environmental and behavioral factors — can help pinpoint the cause of weight gain. Phenomix's phenotypes are based on research from its physician founders, Andres Acosta, MD, PhD and Michael Camilleri, MD of Mayo Clinic, that has demonstrated when patients have been phenotyped and prescribed the right medications, they can achieve up to 16 percent total body weight loss (TBWL). In addition to creating the first biobanking registry of this type, this is the first large scale study to monitor phenotypes in patients with obesity being treated with a variety of treatments. The impact of this biobanking registry and the data it will yield has the potential to change the entire system's approach to obesity, from a treatment recommendation to the way payers determine coverage and how industry combines diagnostics testing with drug therapy. This unique biobanking registry will provide critical and contemporary data on obesity outcomes, impacting every stakeholder in the episode of care, This registry is an important opportunity to make vast strides in how we understand the complexities of obesity treatment. All obesity programs should be seeking the opportunity to participate and contribute to this registry. The more data we have on the variables that contribute to an individual's obesity diagnosis, the more lives we can save by putting the best treatment plan forward. We believe the investment in the biobanking registry will better support obesity centers by providing concrete evidence and insight into how DNA and other factors need to be considered in treatment. Patients can benefit greatly from achieving the desired outcome the first time around, and payers avoid paying for trial-and-error approaches and can reduce overall co-morbid conditions for members." Mark Bagnall, CEO of Phenomix Sciences. About Phenomix Sciences Phenomix Sciences is a biotechnology pioneer on a mission to conquer obesity globally through the science of phenotyping, the understanding of how genes combined with environmental and behavioral factors can inform obesity treatment plans. Mayo Clinic physicians, scientists, and researchers, Andres Acosta, MD, and Michael Camilleri, MD, founded the company under the belief that the key to understanding obesity is unprecedented access to its clinical and molecular information throughout all stages and phenotypes of the disease. Phenomix leverages data intelligence for yielding better accuracy in predicting individual patient response to specific weight loss interventions and reducing the variability in weight loss results for patients.

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CELL AND GENE THERAPY

Research Demonstrates Novel HIT Receptor Enhances T cell Antigen Sensitivity and Elicits Superior Tumor Control

Mnemo Therapeutics | January 24, 2022

The journal Nature Medicine recently published a study in which researchers developed a novel receptor to enhance recognition of tumors by engineered T cells, addressing an underlying cause for relapsed tumors in patients after chimeric antigen receptor therapy. The study demonstrates high antigen sensitivity of HLA-independent T-cell receptors, created by editing the TCR Alpha Constant chain locus in human peripheralbio blood Tcells. Low antigen expression One major limitation of CARs is antigen escape, when a tumor no longer expresses the antigen detectable by the CARs or expresses them at a very low level; CARs with heightened sensitivity to low-expression level antigens boosts the efficacy of otherwise promising T-cell therapies. In the study, conducted by researchers at New York's Memorial Sloan Kettering Cancer Center, researchers produced HIT T-cells and analyzed them in animal models HIT T-cells were engineered from human peripheral blood T-cells by inserting variable region genes in the TRAC locus, endowing the cell with a single specificity for a target antigen such as CD19. Notably, this sensitivity was shown to be higher than traditional CARs for low levels of antigen expression resulting in superior cytotoxicity and cytokine secretion. HIT Tcells outperformed traditional CAR T-cells in vivo in mouse models of B cell leukemia and acute myeloid leukemia, without costimulation. Coexpression of HIT with CD80 and 4-1BBL further augmented therapeutic activity and mouse survival. HIT T-cells are a promising therapy for targeting cancer cell surface antigens with low abundance due to their sensitivity and persistence. The team responsible for this important work includes MSKCC researcher and Mnemo Therapeutics scientific cofounder Michel Sadelain, M.D., Ph.D., MSKCC researcher and Mnemo scientific advisor Isabelle Rivière, Ph.D., as well as Justin Eyquem, Ph.D., University of California San Franciso and Mnemo scientific cofounder. Mnemo's EnfiniT Platform These findings support Mnemo's EnfiniT platform as the next-generation toolkit for CAR-T immunotherapies, which are founded on decades of breakthrough research from Institut Curie and MSKCC, and supported with best-in-class T-cell manufacturing. The EnfiniT platform brings together a suite of technologies to address the key challenges associated with CAR T therapies by both identifying a new class of antigens with greater tumor specificity and applying a range of technologies to significantly improve T-cell memory, persistence and sensitivity. The goal is to dramatically improve the body's ability to fight and overcome disease. About Mnemo Therapeutics Mnemo Therapeutics is a biotechnology company focused on the development of powerful new cell therapies. With its EnfiniT platform, Mnemo applies a novel, integrated approach to T-cell therapy to transform the body's immune response to overcome disease. Mnemo is headquartered in Paris with an office in New York City, and it maintains state of the art laboratories in Paris, New York, and Princeton, New Jersey. The company leverages an international talent pool and global resources in its quest to create accessible cures for all patients in need.

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RESEARCH

Quantgene Demonstrates Game-Changing Sequencing Precision in GENES, A Leading Scientific Journal

Quantgene | June 08, 2021

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