NeuroImmunology
8.2K views | +0 today
Follow
Your new post is loading...
Your new post is loading...
Scooped by Gilbert C FAURE from Cancer Immunotherapy Review and Collection
Scoop.it!

Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients

From www.nature.com - March 13, 2015 4:45 PM

Abstract

 

After stimulation, dendritic cells (DCs) mature and migrate to draining lymph nodes to induce immune responses1. As such, autologous DCs generated ex vivo have been pulsed with tumour antigens and injected back into patients as immunotherapy. While DC vaccines have shown limited promise in the treatment of patients with advanced cancers2, 3, 4 including glioblastoma5, 6, 7, the factors dictating DC vaccine efficacy remain poorly understood. Here we show that pre-conditioning the vaccine site with a potent recall antigen such as tetanus/diphtheria (Td) toxoid can significantly improve the lymph node homing and efficacy of tumour-antigen-specific DCs. To assess the effect of vaccine site pre-conditioning in humans, we randomized patients with glioblastoma to pre-conditioning with either mature DCs8 or Td unilaterally before bilateral vaccination with DCs pulsed with Cytomegalovirus phosphoprotein 65 (pp65) RNA. We and other laboratories have shown that pp65 is expressed in more than 90% of glioblastoma specimens but not in surrounding normal brain9, 10, 11, 12, providing an unparalleled opportunity to subvert this viral protein as a tumour-specific target. Patients given Td had enhanced DC migration bilaterally and significantly improved survival. In mice, Td pre-conditioning also enhanced bilateral DC migration and suppressed tumour growth in a manner dependent on the chemokine CCL3. Our clinical studies and corroborating investigations in mice suggest that pre-conditioning with a potent recall antigen may represent a viable strategy to improve anti-tumour immunotherapy.


Via Krishan Maggon
more...
Krishan Maggon 's curator insight, March 12, 2015 2:41 AM

NATURE | LETTER

Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patientsDuane A. Mitchell,Kristen A. Batich,Michael D. Gunn,Min-Nung Huang,Luis Sanchez-Perez,Smita K. Nair,Kendra L. Congdon,Elizabeth A. Reap,Gary E. Archer,Annick Desjardins,Allan H. Friedman,Henry S. Friedman,James E. Herndon II,April Coan,Roger E. McLendon,David A. Reardon,James J. Vredenburgh,Darell D. Bigner& John H. SampsonAffiliationsContributionsCorresponding authorsNature (2015) doi:10.1038/nature14320Received 06 December 2013 Accepted 13 February 2015 Published online 11 March 2015
Sign up to comment
Scooped by Gilbert C FAURE from Cancer Immunotherapy Review and Collection
Scoop.it!

EU-Funded Consortium led by immatics and BioNTech to Advance a Novel Class of Fully Personalized Therapeutic Cancer Vaccines into Clinical Trials for Brain Cancer / Treatment News / News / CheckOrphan

EU-Funded Consortium led by immatics and BioNTech to Advance a Novel Class of Fully Personalized Therapeutic Cancer Vaccines into Clinical Trials for Brain Cancer / Treatment News / News / CheckOrphan | NeuroImmunology | Scoop.it
From www.checkorphan.org - November 18, 2014 9:31 AM
EU-Funded Consortium led by immatics and BioNTech to Advance a Novel Class of Fully Personalized Therapeutic Cancer Vaccines into Clinical Trials for Brain Cancer

Via Krishan Maggon
more...
Krishan Maggon 's curator insight, October 15, 2014 11:36 AM

GAPVAC was launched in 2013 designed to create, manufacture and develop actively personalized vaccines (APVACs) tailored to the individual characteristics of the patient's tumor and immune system. It is based on combining latest state-of-the-art technologies, including next-generation sequencing (NGS), high-sensitivity mass spectrometry and innovative immunomonitoring approaches to generate an optimal therapy for the individual patient.

 

The consortium is supported by a €6 million grant from the European Union Framework 7 (EU FP7) program.
Sign up to comment
Scooped by Gilbert C FAURE from Alzheimer's Disease R&D Review
Scoop.it!

Molecular Neurodegeneration | Full text | Immunotherapy for Alzheimer's disease: hoops and hurdles

From www.molecularneurodegeneration.com - November 4, 2014 7:57 AM
Alzheimer’s disease (AD) is the most common form of dementia, afflicting more than 30 million people worldwide. Currently, there is no cure or way to prevent this devastating disease.

Via Krishan Maggon
Gilbert C FAURE's insight:
Abstract

.... Extracellular plaques, containing various forms of amyloid-β protein (Aβ), and intracellular neurofibrillary tangles (NFTs), composed of hyper-phosphorylated tau protein, are two major pathological hallmarks of the AD brain. Aggregation, deposition, and N-terminal modification of Aβ protein and tau phosphorylation and aggregation are thought to precede the onset of cognitive decline, which is better correlated with tangle formation and neuron loss. Active and passive vaccines against various forms of Aβ have shown promise in pre-clinical animal models. However, translating these results safely and effectively into humans has been challenging. Recent clinical trials showed little or no cognitive efficacy, possibly due to the fact that the aforementioned neurodegenerative processes most likely pre-existed in the patients well before the start of immunotherapy. Efforts are now underway to treat individuals at risk for AD prior to or in the earliest stages of cognitive decline with the hope of preventing or delaying the onset of the disease. In addition, efforts to immunize against tau and other AD-related targets are underway.

more...
Krishan Maggon 's curator insight, November 2, 2014 1:56 AM

Review

Immunotherapy for Alzheimer’s disease: hoops and hurdles

Cynthia A Lemere

Correspondence: Cynthia A Lemere clemere@partners.org

Author Affiliations

Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, NRB 636F, 77 Avenue Louis Pasteur, Boston 02115, MA, USA

Molecular Neurodegeneration 2013, 8:36  doi:10.1186/1750-1326-8-36


The electronic version of this article is the complete one and can be found online at:http://www.molecularneurodegeneration.com/content/8/1/36


Received:3 July 2013Accepted:23 September 2013Published:22 October 2013

© 2013 Lemere; licensee BioMed Central Ltd. 

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Sign up to comment
About Follow us Resources Terms Mobile Features
Facebook
X
LinkedIn