Breaking News
April 20, 2018 - Cancer Australia launches new framework to improve outcomes for lung cancer patients
April 20, 2018 - ‘Gut-on-a-chip’ model recreates intestinal matrix critical for nutrient absorption
April 20, 2018 - Researchers develop new drug-testing platform for epilepsy
April 20, 2018 - FDA Alert: NxtGen Botanicals Maeng Da Kratom by NGB Corp.: Recall
April 20, 2018 - Pelizaeus-Merzbacher-like disease type 1 – Genetics Home Reference
April 20, 2018 - Tick-borne diseases reach epidemic levels, panel says
April 20, 2018 - A potential “male pill” without side effects
April 20, 2018 - Researchers discover new information related to rare form of leukemia
April 20, 2018 - Researchers find crucial links between dopamine and avoidance behavior
April 20, 2018 - UGA scientist creates system for efficient detection of foodborne pathogens
April 20, 2018 - Social Support of Autonomy Tied to Better Glycemic Control in DM
April 20, 2018 - Study reports use of nutritional ketosis with mobile app intervention could reverse Type 2 diabetes
April 20, 2018 - New microscopy techniques allow quasi-biochemical studies on living T cells
April 20, 2018 - Study shows connection between muscular strength and brain health
April 20, 2018 - Ecolab introduces Life Sciences cleanroom program in North America
April 20, 2018 - Male fruit flies like sex and alcohol
April 20, 2018 - Improving job prospects unlikely to control opioid epidemic
April 20, 2018 - Skin Sensor Might Someday Track Alcoholics’ Booze Intake
April 20, 2018 - The relevance of GABA for diabetes highlighted in two new studies
April 20, 2018 - Novel method enables fast and noninvasive assessment of tumor status
April 20, 2018 - IU psychologist receives NIH grant to study earliest phases of language learning in children
April 20, 2018 - Walking fast lowers risk of hospitalization in heart patients, shows study
April 20, 2018 - Young victims of cyberbullying twice as likely to attempt suicide and enact suicidal behavior
April 20, 2018 - Role of UBE3A enzyme in Angelman syndrome
April 20, 2018 - NovaDigm Therapeutics initiates NDV-3A Phase 2a study for reduction of S. aureus in military trainees
April 20, 2018 - High-tech microscope reveals how cancer-causing virus anchors itself to human DNA
April 20, 2018 - Experimental compound reduces destructive inflammation to improve stroke outcome
April 20, 2018 - The May issue of Drug Discovery Today is a Special Issue and will be published very soon
April 20, 2018 - Larger families linked to heightened tooth loss risk for moms
April 20, 2018 - Scientists develop tiny fluorescent probe that seeks out GLUT5 and detects cancer cells
April 20, 2018 - The Swedish Childhood Cancer Foundation awards grant to KI researchers
April 20, 2018 - AMSBIO’s MC-Easy minicircle technology allows sustained transgene expression in quiescent cells and tissues
April 20, 2018 - Researchers use optogenetics to treat chronic pain
April 20, 2018 - Discovery of 100 new genes may aid research into pigmentation
April 20, 2018 - AYOXXA introduces new LUNARIS Mouse 12-Plex Th17 Kit for quantitative analysis of Th17 cell biology
April 20, 2018 - Compound derived from immune cells treats psoriasis in mice
April 20, 2018 - GABA-transaminase deficiency – Genetics Home Reference
April 20, 2018 - Key heart risks decline for older Americans
April 20, 2018 - UD professor wins $2.3 million grant from NIH for research on Achilles tendinopathy
April 20, 2018 - Researchers discover unique protein in malaria parasite that could be new drug target
April 20, 2018 - Bio-Techne expands automation capabilities of popular RNAscope ISH technology
April 20, 2018 - Smartphone app effective in promoting proper child car seat practices
April 20, 2018 - Nutraceuticals could play an important role in preventing heart disease
April 20, 2018 - FDA Alert: Certain Kratom-Containing Powder Products by Viable Solutions: Recall -Possible Salmonella Contamination
April 20, 2018 - What is heart failure?
April 20, 2018 - TIP Biosystems introduces handheld UV-Visible spectrophotometer for photometric measurements
April 20, 2018 - Inactivity of astronauts during spaceflights may have more pronounced effect on skeletal muscle than hypoxia
April 20, 2018 - New SIDS Info app seeks to reduce infant sleep-related deaths
April 20, 2018 - Wide-scale distribution of naloxone effectively prevents overdose deaths, study finds
April 20, 2018 - Triple-negative breast cancer found to be chemoresistant prior to treatment
April 20, 2018 - ACL tears occur the same way in women and men, study finds
April 20, 2018 - UT Southwestern researchers identify 170 potential therapeutic targets for lung cancer
April 20, 2018 - Finding the ‘keyhole’ to beat obesity at the cellular level
April 20, 2018 - Long-term exposure to cold temperatures reduces diabetes and obesity, shows study
April 20, 2018 - Metabolic Syndrome Common With Chronic Hep B Infection
April 20, 2018 - Tracking quality of life during prostate cancer treatment
April 20, 2018 - Study shows presence of beta-amyloid dimers in the brains of Alzheimer’s patients
April 20, 2018 - Researchers identify link between physical inactivity and increased risk of dying from cancer
April 20, 2018 - Breathtaking evolution amongst Indonesian tribe
April 20, 2018 - Study shows testosterone deficiency in men is associated with chronic diseases
April 20, 2018 - Simple one-page form helps improve satisfaction of patients with care
April 20, 2018 - Researchers evaluate accuracy of simple blood test to predict lung cancer
April 20, 2018 - Study looks at sperm producing ability in testicular cancer patients
April 20, 2018 - Exercise In, Vitamin D Out for Preventing Falls: U.S. Panel
April 20, 2018 - Skin cancers associated with decreased risk of developing AD
April 20, 2018 - Preserving fertility during chemotherapy
April 20, 2018 - Teva and Procter & Gamble Company terminate PGT Healthcare partnership
April 20, 2018 - People diagnosed with traumatic brain injury may have increased risk of Parkinson’s disease, shows study
April 20, 2018 - Researchers use smartphone to diagnose people infected with Loa loa worm
April 20, 2018 - College students with autism have high rate of suicidal thoughts
April 20, 2018 - Study sheds light on how the HSC niche is maintained
April 20, 2018 - Drug test spurs frank talk between hypertension patients and doctors
April 19, 2018 - Low-cost deworming drug improves female farmers’ physical fitness
April 19, 2018 - Genome editing identifies neural circuit behind leptin’s anti-obesity and anti-diabetes effects
April 19, 2018 - Many European countries lack comprehensive policy to eliminate viral hepatitis
April 19, 2018 - Young people with ADHD ‘more likely’ to come from deprived neighbourhoods
April 19, 2018 - SLU professor discovers new biomarkers for chlorine gas exposure
April 19, 2018 - Study proposes new mechanism that may contribute to gender differences in weight control
April 19, 2018 - Sleep restriction therapy does not interfere with insomnia patient’s driving ability, research shows
April 19, 2018 - Deep brain stimulation offers relief to UTHealth patient with treatment-resistant depression
Combined treatment prolongs survival in mouse models of malignant mesothelioma

Combined treatment prolongs survival in mouse models of malignant mesothelioma

image_pdfDownload PDFimage_print

Combined treatment with two cancer immunotherapy drugs – one a novel immune modulator and one that focuses and activates the antitumor immune response – significantly prolonged survival in mouse models of the aggressive cancer malignant mesothelioma. In their report published in Cancer Immunology Research, a team from the Vaccine and Immunotherapy Center (VIC) at Massachusetts General Hospital (MGH) describes how adding AMD3100 (plerixafor) – previously approved for the stimulation of stem cell production prior to bone marrow transplantation – to their investigational drug VIC-008 more than doubled the animals’ survival time. Among the mechanisms identified as underlying the combination treatment’s effects was changing a population of immunosuppressive T cells into a type that could enhance an antitumor immune response.

“Mesothelioma, a tumor that is caused by asbestos exposure, has been extremely hard to treat; and patients usually survive only 12 to 18 month after diagnosis,” says Mark Poznansky, MD, PhD, director of the MGH-VIC and senior author of the report. “Since the advent of cancer immunotherapy, people have tried to apply immunotherapeutic drugs to mesothelioma with limited success. We are very excited at the prospect that this drug combination may be much more effective in prolonging patients’ lives.”

The study is the result of a collaboration between Poznansky and Jeffrey Gelfand, MD, an MGH-VIC investigator who had developed VIC-008 – also called Jantibody, in memory of Gelfand’s wife Janet who succumbed to ovarian cancer – as a potential treatment for ovarian cancer. VIC-008 is a fusion protein combining an immune-activating protein from the tuberculosis bacteria with a small antibody fragment targeting mesothelin, a protein expressed in several types of tumor – including mesothelioma, pancreatic and ovarian cancer. While previous research had shown some effectiveness of this molecule in a mouse model of ovarian cancer, that benefit was limited by the immunosuppressive environment within tumors, particularly the presence of regulatory T cells (Tregs). The current combination appears to overcome this limitation.

Poznansky’s team – with lead scientist Huabiao Chen, PhD, corresponding author of the current report – had been investigating applications of AMD3100, a drug that blocks the CXCR4/CXCR12 signaling pathway known to be involved in cancer development and in the way in which mesothelioma evades the immune system. While research has supported AMD3100’s ability to inhibit tumor growth and metastasis, the mechanism behind its effects on mesothelioma had not been determined. Since expression of CXCR4 and CXCR12 are increased as mesothelioma progresses, VIC researchers investigated the potential of combining AMD3100 with VIC-008 to treat these tumors.

Their series of experiment in two different mesothelioma mouse models found the following:

  • While single-agent treatment with either drug had limited effects against mesothelioma, treatment with both drugs significantly reduced tumor size and prolonged the animals’ survival.
  • Treatment with VIC-008 increased lymphocyte infiltration of tumors and both the levels and the anti-tumor response of CD8 T cells, which kill damaged or infected cells.
  • AMD3100, alone or in combination with VIC-008, decreases expression of the immune checkpoint molecule PD-1 on CD8 T cells, implying that the CXCR4/CXCR12 pathway modulates PD-1 expression.
  • AMD3100, alone or in combination, reduced the number of tumor-infiltrating Treg cells and increased the proportion of CD8 T cells.
  • AMD3100 further reduces immune suppression by shifting characteristics of Tregs toward those of helper T cells, which would enhance antitumor effects.

“The apparent ability to change immunosuppressive T cells within the tumor into T cell types that are more active and potentially helpful against cancer was a really exciting finding, and one that we’re continuing to investigate,” says Poznansky, who is an associate professor of Medicine at Harvard Medical School (HMS).

Chen adds, “We believe that we can find an approach that combines Jantibody and AMD3100 to regroup and redirect immune responses in order to combat cancer.” He is an instructor in Medicine at HMS.

Gelfand, a senior scientist at VIC and professor (part-time) at HMS, says, “AMD3100 is already an FDA-approved drug, whose use and application the MGH VIC is hoping to extend in various cancers. Jantibody focuses the AMD3100-invigorated immune response on critical tumor structures, markedly enhancing tumor control. We hope these data will help to move Jantibody closer to human tumor therapy, fulfilling one of my wife’s last wishes.”

Source:

http://www.massgeneral.org/about/pressrelease.aspx?id=2236

Tagged with:

About author

Related Articles