Breaking News
September 25, 2018 - Vaping among kids and teens a growing concern
September 25, 2018 - Public launch of products and application solutions from Porvair Laboratory Division
September 25, 2018 - Harmful H. pylori may play a role in Parkinson’s disease
September 25, 2018 - Researchers develop way to measure different types of fear of falling in patients with Parkinson’s
September 25, 2018 - Fracture causes bone density losses throughout the body
September 25, 2018 - Researchers highlight potential therapy for treating rare, deadly blood-clotting disorder
September 25, 2018 - Hybrid theranostic complex shows high therapeutic efficacy against tumor cells
September 25, 2018 - FDA Issues Statement Reaffirming the Positive Benefit-Risk Profile of Nuplazid (pimavanserin) for Patients with Hallucinations and Delusions Associated with Parkinson’s Disease Psychosis
September 25, 2018 - Toxicological evaluation and dosimetry estimation of potential PET radiotracer
September 25, 2018 - 5 obstacles parents commonly face in child obesity treatment and how to overcome them
September 25, 2018 - Immunologist to study how Chikungunya causes devastating effects in older adults
September 25, 2018 - Rural borderland communities vulnerable to high stress impacting mental and physical health
September 25, 2018 - SNMMI announces recipients of 2018-2020 Wagner-Torizuka Fellowship
September 25, 2018 - Common painkiller not effective in controlling chronic pain after traumatic nerve injury
September 25, 2018 - New therapeutic vaccine helps immune cells fight HPV-related head and neck cancer
September 25, 2018 - Environmentally-induced gene activity influences IQ test performance
September 25, 2018 - Biogen and Eisai announce results of LTE Phase 1b study of aducanumab for treating MCI
September 25, 2018 - FDA Approves Copiktra (duvelisib) Capsules for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Follicular Lymphoma
September 25, 2018 - Medical device company settles US case over false claims
September 25, 2018 - Trying to get answers: One woman’s quest for a diagnosis
September 25, 2018 - Lung cancer patients treated with invasive surgery more likely to become chronic opioid users
September 25, 2018 - Oxford VR raises £3.2m to boost innovation in VR for mental health problems
September 25, 2018 - Gene therapy approach could help treat mitochondrial diseases
September 25, 2018 - Few Yogurt Products Qualify As Low-Sugar
September 25, 2018 - Eye disease can cause blindness, and it’s on the rise
September 25, 2018 - Pawnshop density linked to gun-related suicides, Stanford study finds
September 25, 2018 - Pioneering procedure for common prostate condition offered by The London Clinic
September 25, 2018 - Number of people with respiratory diseases likely to increase if UK air pollution remains unchecked
September 25, 2018 - FARXIGA receives positive results in Phase III DECLARE-TIMI 58 cardiovascular outcomes trial
September 25, 2018 - New program to reduce harmful stress effectively improves mood in cancer patients
September 24, 2018 - Florence’s Lingering Threat: Mold – Drugs.com MedNews
September 24, 2018 - For professional baseball players, faster hand-eye coordination linked to batting performance
September 24, 2018 - Bill for later school start times is defeated, but Stanford sleep specialist isn’t
September 24, 2018 - For Heart Failure Patients, Mitral Valve Procedure Improved Outcomes
September 24, 2018 - Successful recovery from addiction means more than achieving abstinence
September 24, 2018 - New nanoplatform technology may reverse drug-resistance in renal cell carcinoma
September 24, 2018 - October 1918 marks the centenary of Spanish Flu that claimed more lives than World War I
September 24, 2018 - LGBT community reports more number of poor mental health days than general population
September 24, 2018 - New research suggests power of zebrafish as tool for cancer drug discovery
September 24, 2018 - New study finds height as possible risk factor for developing varicose veins
September 24, 2018 - Researchers compare weight loss results of online and in-person diabetes prevention program
September 24, 2018 - New HER2 PET Study Uses Affibody’s ABY-025 Tracer to Individualize Breast Cancer Treatment
September 24, 2018 - Drug combination offers more effective care for patients suffering miscarriage
September 24, 2018 - Tallness linked to varicose veins, Stanford study says
September 24, 2018 - For Heart Failure Patients, Mitral Valve Procedure Improved Outcomes
September 24, 2018 - Ecstasy drug makes octopuses more social
September 24, 2018 - Immediate compression therapy could cut risk of complications after deep-vein thrombosis
September 24, 2018 - Transcatheter mitral valve repair reduces mortality for patients with mitral regurgitation
September 24, 2018 - First intracranial aneurysm patients treated with BRAVO Flow Diverter after CE mark approval
September 24, 2018 - ‘Physicians of the mouth’? Dentists absorb the medical billing drill
September 24, 2018 - People more likely to believe those with confident tone of voice than with accent
September 24, 2018 - Harmony Biosciences Presents 5-Year Data On Pitolisant At International Narcolepsy Symposium
September 24, 2018 - Blood test may identify gestational diabetes risk in first trimester
September 24, 2018 - Height may be risk factor for varicose veins | News Center
September 24, 2018 - King’s commemorates opening of new NMR facility with one-day symposium
September 24, 2018 - Eisai receives approval for partial label change of DC Bead device for transcatheter arterial embolization
September 24, 2018 - Using multi-level approach to reduce underage drinking among youths on rural reservations
September 24, 2018 - High-resolution genomic map gives scientists unprecedented view of brain development
September 24, 2018 - Researchers find impact of neurobehavioral symptoms on employment in adults with TBI
September 24, 2018 - Alexion announces positive results from Phase 3 PREVENT study of Soliris in patients with NMOSD
September 24, 2018 - First evaluation of benefits, harms of Alzheimer’s screening for family members of older adults
September 24, 2018 - Ancora Heart announces positive data of study evaluating AccuCinch Ventricular Repair System
September 24, 2018 - Children of mothers using cannabis may start using it at an earlier age, finds study
September 24, 2018 - Gilead Sciences plans to launch authorized generic versions of Epclusa and Harvoni in the US
September 24, 2018 - Most patients who underwent transcatheter valve replacement experience prosthesis-patient mismatch
September 24, 2018 - Lumos acquires license for LUM-201 drug that promotes secretion of growth hormone
September 24, 2018 - New study provides basis for Air Canada to change its facial hair policy for aircrew
September 24, 2018 - Infant walkers lead to thousands of emergency visits for babies
September 24, 2018 - Genes predicting person’s height may provide clues about causes of varicose veins
September 24, 2018 - EPA Plan Will Maintain Carbon Emissions From Power Plants
September 24, 2018 - Characterizing pig hippocampus could improve translational neuroscience
September 24, 2018 - Element3 Health reports social and mental engagement play key role in overall health
September 24, 2018 - Paralympic medalists support Fight for Sight’s unique virtual event
September 24, 2018 - ADCETRIS drug receives approval in Japan as frontline treatment option for Hodgkin lymphoma
September 24, 2018 - Public awareness of urological conditions found to be alarmingly low across Europe
September 24, 2018 - Fitter Folks Suffer Milder Strokes: Study
September 24, 2018 - Novel botulinum toxin compound relieves chronic pain
September 24, 2018 - CHMP recommends approval of Gilenya for treatment of multiple sclerosis in children, adolescents
September 24, 2018 - National Friendly’s private medical insurance is a hit with women living in the South East
September 24, 2018 - Academics receive prestigious awards for achievements in blood pressure research
Customising T-cells for cancer immunotherapy

Customising T-cells for cancer immunotherapy

image_pdfDownload PDFimage_print

Immunotherapy involves the modification of immune cells to stimulate an immune response for the treatment or prevention of disease. In the case of cancer therapies, the aim is to induce an immune response that targets and kills the cancerous cells whilst avoiding damage to healthy cells.

Image Credit: royaltystockphoto / Shutterstock

There are two types of T cells (CD4+ and CD8+). CD8+ T-cells recognize  foreign or pathogen-derived proteins called antigens. These pathogens are processed by antigen presenting cells into peptides and presented on molecules called major histocompatibility complexes (MHCs). This allows T-cells to induce an immune response.

T-cell receptors (TCRs) have different affinities for different antigen peptides. Only TCRs with a high affinity will induce an immune response. Natural anti-cancer TCRs have low affinity so methods to generate TCRs with a higher affinity to cancerous cells must be used.

Using therapeutic T-cells for cancer immunotherapy isn’t straightforward. For the therapy to be an effective form of treatment, T-cells must be:

  • Trafficked to the site of a tumor
  • Overcome immunosuppression
  • Target all tumor cells
  • Not affect healthy tissues
  • Safe for use on a wide range of patients

This may seem like a tall order, but recent advances in synthetic biology and genome editing offer great potential to solve these problems.

Recent studies have investigated the ability to design a CD8+ T-cell that can target and kill cancerous cells efficiently.

A method that increases the affinity of TCRs involves displaying a library of TCRs on the surface of a bacteriophage, then performing several rounds of precise selection using immobilized peptide-MHC complexes. This increases the affinity of TCRs by directing the evolution of them to increase the TCR-peptide-MHC affinity.

In the thymus, immature T-cells undergo various stages of development and can become CD8+ T-cells. These T-cells interact with self-antigens and MHCs. T-cells with affinity too high are destroyed and ones with too low affinity die.

Another method used to generate higher affinity anti-cancer T-cells is to bypass the thymic selection stage of T-cell development. These T-cells have not undergone clonal selection, and thus comprise high affinity cancer-specific TCRs.

This has previously been achieved through the generation of ‘humanized’ mice which express a mouse MHC allele and the human TCR. Since these mice contain no human antigens, the human reactive TCRs are not deleted.

Modifying T-cells to target cancer cells can provide an alternative to existing cancer immunotherapies, such as checkpoint inhibitors. However, more research is needed in the field of T-cell immunotherapy in order to develop efficacious, targeted cancer therapies.

Source:

Legut, M. and Sewell, A. (2018). Designer T-cells and T-cell receptors for customized cancer immunotherapies. Current Opinion in Pharmacology, 41, pp.96-103.

Tagged with:

About author

Related Articles