Breaking News
May 25, 2018 - Melorheostosis – Genetics Home Reference
May 25, 2018 - Non-addictive pain medication changing therapy for substance use disorders
May 25, 2018 - Delayed lactate measurements in sepsis patients increase risk of in-hospital death
May 25, 2018 - Researchers identify novel epigenetic mutations as cause of neurodevelopmental, congenital disorders
May 25, 2018 - UD researchers examine connection between DNA replication in HPV and cancer
May 25, 2018 - Researchers identify neurons that play key role in aggressive behavior
May 25, 2018 - Researchers discover unexpected chemosensor pathway for predator odor-evoked innate fear behaviors
May 25, 2018 - Nearly one in three people know someone addicted to opioids
May 25, 2018 - New findings could help fine-tune treatment for cancer patients
May 25, 2018 - New cancer treatment approach targets specific sugar receptors
May 25, 2018 - Skin responsible for uptake of cancer-causing compounds during barbecuing than lungs
May 25, 2018 - Early-onset cannabis use linked to further drug abuse problems
May 25, 2018 - Covered California takes aim at hospital C-section rates
May 25, 2018 - FDA Approves Palynziq (pegvaliase-pqpz) for the Treatment of Adults with Phenylketonuria
May 25, 2018 - Arthritis Glossary
May 25, 2018 - Study links breast cancer to the body’s internal clock
May 25, 2018 - Strenuous exercise in teenage years may protect against height loss later in life
May 25, 2018 - FDA approves novel enzyme therapy for adults with rare and serious genetic disease
May 25, 2018 - New research project aims at developing effective interventions for kids with DLD
May 25, 2018 - Middlemen who save $$ on medicines — but maybe not for you
May 25, 2018 - Study sheds new light on sharp rise in fatal drug overdoses in recent years
May 25, 2018 - Students propose revision of listeriosis guidelines for safer pregnancy
May 25, 2018 - TNFi Exposure In Utero Does Not Up Serious Infection Risk
May 25, 2018 - Organization of cells in the inner ear enables the sense and sensitivity of hearing
May 25, 2018 - Yoga May Be Right Move Against Urinary Incontinence
May 25, 2018 - Drinking recommended amount of milk could protect obese children against metabolic syndrome
May 25, 2018 - New cytokine network can repair tissue damage in the intestine, study finds
May 25, 2018 - Lyme disease researcher dispels misconceptions about ticks and provides prevention tips
May 25, 2018 - Penn researchers find link between social media usage and underage drinking
May 25, 2018 - Unique nanotechnology method to simplify skin disease diagnosis
May 25, 2018 - Study reveals new protective mechanism for tumor cells in breast cancer
May 25, 2018 - FRAME Alternatives Laboratory chosen for major European liver research collaboration
May 25, 2018 - Study shows yogurt may dampen chronic inflammation linked to multiple diseases
May 25, 2018 - Invasive cancers that are born to be bad show detectable differences from harmless tumors
May 25, 2018 - Study identifies new mechanism involved in development of Lou Gehrig’s disease
May 25, 2018 - UAB professor receives award for malaria prevention study in pregnant women in Cameroon
May 25, 2018 - Study provides blueprint of how fruit flies can be used to screen potentially pathogenic human genes
May 25, 2018 - New drug-delivering nanoparticle could offer better way to treat brain tumors
May 25, 2018 - Kessler Foundation scientists compare two tests for assessing learning in individuals with MS
May 25, 2018 - Stroke Symptoms and Diagnosis (Beyond the Basics)
May 25, 2018 - Protein goes against the family to prevent cancer
May 25, 2018 - Drugmakers blamed for blocking generics have milked prices and cost U.S. billions
May 25, 2018 - Speakers announced for National Medicines Symposium 2018
May 25, 2018 - GSK Receives FDA Approval of Arnuity Ellipta for Asthma in Children From 5 Years of Age
May 25, 2018 - Pfizer settles kickback case related to copay assistance for $24m
May 25, 2018 - Nuclear pore functions are essential for T cell survival
May 25, 2018 - Study defines molecular basis to explain connection between mother’s nutrition and infant growth
May 24, 2018 - IHI hosts representatives to develop a national action plan for patient safety
May 24, 2018 - Zika detection breakthrough by University of Queensland
May 24, 2018 - FDA Alert: 95% Ethyl Alcohol Product by Ethanol Extraction: Recall
May 24, 2018 - New method allows scientists to study how HIV persists
May 24, 2018 - Study reveals rate of vertebral and non-vertebral fractures in children with leukemia
May 24, 2018 - Whey protein supplementation and physical activity aid women in improving body composition
May 24, 2018 - Seniors’ air pollution exposure linked to hospitalization for ARDS
May 24, 2018 - Home-based telehealth therapy program effective for stroke rehabilitation, shows study
May 24, 2018 - Addressing Parents’ HPV Vaccine Hesitancy Ups Vaccination Rates
May 24, 2018 - Opioid addiction treatment drug helps suppress HIV in former prisoners
May 24, 2018 - FDA warns against using teething remedies for babies
May 24, 2018 - Healthy lifestyle counseling program linked to reduced risk of developing cancers
May 24, 2018 - CU research sheds light on liver disease caused by intravenous nutrition
May 24, 2018 - Skin cream containing rapamycin reduces TSC-related facial tumors
May 24, 2018 - Suicide rates twice as high among black children finds new study
May 24, 2018 - Researchers find new method to treat severe asthma
May 24, 2018 - Scientists report new strategy for fighting bacteria
May 24, 2018 - South Asians living in the United States more likely to die of heart disease and stroke
May 24, 2018 - Health Tip: Why Get a Biopsy
May 24, 2018 - Metabolic Syndrome Prevalence by Race/Ethnicity and Sex in the United States, National Health and Nutrition Examination Survey, 1988–2012
May 24, 2018 - Motivation to move may start with being mindful
May 24, 2018 - Advanced genetics study of TB bacteria uncovers virulent ‘Beijing lineage’ strain among young adults
May 24, 2018 - Friends tend to have similar pain tolerance levels, study reveals
May 24, 2018 - International researchers succeed in stopping growth of mesothelioma in model animals
May 24, 2018 - Inactive people find high-intensity interval training to be as enjoyable as traditional exercise
May 24, 2018 - Now more of us can count on more time dodging the dementia bullet
May 24, 2018 - Scientists develop new test to predict woman’s risk of preterm birth
May 24, 2018 - Global healthcare access and quality improved from 2000-2016
May 24, 2018 - Virtual follow-up visits for hypertension care just as effective as in-person office visits
May 24, 2018 - New research reveals links between type 1 diabetes and mental health
May 24, 2018 - Antioxidant-enriched multivitamin may decrease respiratory illnesses in CF patients, finds study
May 24, 2018 - Antidepressant treatments increase risk of weight gain, study finds
May 24, 2018 - INSYS Therapeutics Confirms Outcome of FDA Advisory Committee Meeting on Buprenorphine Sublingual Spray
Researchers use immune-mimicking biomaterial scaffolds to fast track T cell therapies

Researchers use immune-mimicking biomaterial scaffolds to fast track T cell therapies

image_pdfDownload PDFimage_print

Immunologists and oncologists are harnessing the body’s immune system to fight cancers and other diseases with adoptive cell transfer techniques. In a normal immune response, a type of white blood cell known as T cells are instructed by another kind of immune cell called an antigen-presenting cell (APC) to expand their numbers and stay alive. Adoptive cell transfer procedures are mimicking exactly this process in a culture dish by taking T cells from patients, multiplying them, sometimes genetically modifying them, and then returning them to patients so that they can, for example, locate and kill cancer cells. However, these procedures often take weeks to produce batches of therapeutic T cells that are large and reactive enough to be able to eliminate their target cells.

A team led by David Mooney at Harvard’s Wyss Institute for Biologically Inspired Engineering and John A. Paulson School of Engineering and Applied Sciences (SEAS) is now reporting in Nature Biotechnology an alternative material-based T-cell-expansion method that could help surmount these obstacles. With an APC-mimetic biomaterial scaffold, the researchers achieved greater expansion of primary mouse and human T cells than with existing methods; and they demonstrated the approach’s potential in a mouse lymphoma model treated with chimeric antigen receptor-expressing T cells (CAR-T cells) that are engineered to home in on and destroy lymphoma cells.

“Our approach closely mimics how APCs present their stimulating cues to primary T cells on their outer membrane and how they release soluble factors that enhance the survival of the T cells. As a result, we achieve much faster and greater expansion. By varying the compositions of lipids, cues, and diffusible factors in the scaffolds, we engineered a very versatile and flexible platform that can be used to amplify specific T cell populations from blood samples, and that could be deployed in existing therapies such as CAR-T cell therapies,” said Mooney, Ph.D., a Core Faculty member at the Wyss Institute and leader of its Immunomaterials Platform. Mooney is also the Robert P. Pinkas Family Professor of Bioengineering at SEAS.

To engineer an APC-mimetic scaffold, the team first loaded tiny mesoporous silica rods (MSRs) with Interleukin 2 (IL-2) ¬– an APC-produced factor that prolongs the survival of associated T cells. The MSRs were then coated with lipids that formed a thin supported lipid bilayer (SLB), which resembles the outer membrane of APCs and that the researchers then functionalized with a pair of T cell-stimulating antibodies that remain mobile in the lipid layer and can bind to receptor/co-receptor molecules on the surface of T cells. In culture medium, 3D scaffolds spontaneously formed through the settling and random stacking of the rods, forming pores big enough to allow the entry, movement, and accumulation of T cells, thereby signaling them to multiply.

In a series of side-by-side comparisons, Mooney’s team demonstrated that APC-mimetic scaffolds performed better than methods involving commercially available expansion beads (Dynabeads), which are currently used in clinical adoptive cell transfer approaches. “In a single dose, APC-mimetic scaffolds led to two- to ten-fold greater expansion of primary mouse and human T cells than Dynabeads. As another advantage, APC-mimetic scaffolds enabled us to tune the ratios of subpopulations of T cells with different roles in the desired immune responses, which in the future might increase their functionality,” said David Zhang, the study’s second author and a Graduate Student working with Mooney.

Building on these findings, the researchers demonstrated the utility of their T cell expansion platform in a therapeutic model. “Prompted by recent breakthroughs in CAR-T cell therapies, we showed that a specific CAR-T cell product expanded with an APC-mimetic scaffold could facilitate treatment of a mouse model of a human lymphoma cancer,” said first author Alexander Cheung, Ph.D., who started the project in Mooney’s team and now is a scientist at UNUM Therapeutics in Cambridge, Massachusetts. An APC-mimetic scaffold that was engineered to activate a specific type of CAR-T cell was able to generate higher numbers of the modified T cells over longer periods of culture than analogously designed expansion beads, and the resulting cells were similarly effective in killing the lymphoma cells in the mice.

After successfully using the material to expand all T cells present in a sample, the team demonstrated that APC-mimetic scaffolds could also be used to expand antigen-specific T cell clones from a more complex mixture of cells. Such T cell clones are constantly developed by the immune system to recognize small specific peptides contained in foreign proteins. To this aim, the researchers incorporated molecules into the scaffolds that are known as the major histocompatibility complex (MHC) and that presented small peptides derived from viral proteins to T cells.

“Based also on studies in which we showed that APC-mimetic scaffolds also have superior potential to specifically enrich and expand rare T cell sub-populations from blood, we strongly believe that we created an effective platform technology that could facilitate more effective precision immunotherapies,” said Cheung.

“The bioinspired T cell-activating scaffolds developed by the Wyss Institute’s Immunomaterials Platform could accelerate the success of many immunotherapeutic approaches in the clinic, with life-saving impact on a broad range of patients, in addition to advancing personalized medicine,” said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at SEAS.

Source:

https://wyss.harvard.edu/fast-tracking-t-cell-therapies-with-immune-mimicking-biomaterials/

Tagged with:

About author

Related Articles