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Exploiting in situ antigen generation and immune modulation to enhance chemotherapy response in advanced melanoma: A combination nanomedicine approach

Therapeutic anticancer vaccine development must address a number of barriers to achieve successful tumor specific killing, including effective antigen presentation and antigen-specific T-cell activation to mediate cytotoxic cellular effects, inhibition of an immune-suppressive tumor microenvironment... Full description

Journal Title: Cancer Letters 28 August 2016, Vol.379(1), pp.32-38
Main Author: Lu, Yao
Other Authors: Wang, Yuhua , Miao, Lei , Haynes, Matthew , Xiang, Guangya , Huang, Leaf
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0304-3835 ; E-ISSN: 1872-7980 ; DOI: 10.1016/j.canlet.2016.05.025
Link: https://www.sciencedirect.com/science/article/pii/S030438351630338X
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recordid: elsevier_sdoi_10_1016_j_canlet_2016_05_025
title: Exploiting in situ antigen generation and immune modulation to enhance chemotherapy response in advanced melanoma: A combination nanomedicine approach
format: Article
creator:
  • Lu, Yao
  • Wang, Yuhua
  • Miao, Lei
  • Haynes, Matthew
  • Xiang, Guangya
  • Huang, Leaf
subjects:
  • Cisplatin Nanoparticle
  • Cpg-Odn
  • Melanoma
  • Immunotherapy
  • Chemotherapy
  • Medicine
ispartof: Cancer Letters, 28 August 2016, Vol.379(1), pp.32-38
description: Therapeutic anticancer vaccine development must address a number of barriers to achieve successful tumor specific killing, including effective antigen presentation and antigen-specific T-cell activation to mediate cytotoxic cellular effects, inhibition of an immune-suppressive tumor microenvironment in order to facilitate and enhance CTL activity, and induction of memory T-cells to prolong tumor rejection. While traditional as well as modern vaccines rely upon delivery of both antigen and adjuvant, a variety of clinically relevant cancers lack ideal immunogenic antigens. Building upon recent efforts, we instead chose to exploit chemotherapy-induced apoptosis to allow for antigen generation in a combination, nanomedicine-based approach. Specifically, lipid-coated cisplatin nanoparticles (LPC) and CpG-encapsulated liposomes (CpG-Lipo) were prepared for the temporally-controlled and multifaceted treatment of an advanced model of melanoma. Such combination therapy established strong synergistic effects, both in apoptotic extent and subsequent abrogation of tumor growth, which were due largely to both an enhanced cytotoxic T-cell recruitment and a reduction of immune-suppressive mediators in the microenvironments of both spleens and tumor. These results underlie a prolonged host lifespan in the combination approach (45 days) as compared with control (25 days, p 
language: eng
source:
identifier: ISSN: 0304-3835 ; E-ISSN: 1872-7980 ; DOI: 10.1016/j.canlet.2016.05.025
fulltext: fulltext
issn:
  • 0304-3835
  • 03043835
  • 1872-7980
  • 18727980
url: Link


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titleExploiting in situ antigen generation and immune modulation to enhance chemotherapy response in advanced melanoma: A combination nanomedicine approach
creatorLu, Yao ; Wang, Yuhua ; Miao, Lei ; Haynes, Matthew ; Xiang, Guangya ; Huang, Leaf
ispartofCancer Letters, 28 August 2016, Vol.379(1), pp.32-38
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subjectCisplatin Nanoparticle ; Cpg-Odn ; Melanoma ; Immunotherapy ; Chemotherapy ; Medicine
descriptionTherapeutic anticancer vaccine development must address a number of barriers to achieve successful tumor specific killing, including effective antigen presentation and antigen-specific T-cell activation to mediate cytotoxic cellular effects, inhibition of an immune-suppressive tumor microenvironment in order to facilitate and enhance CTL activity, and induction of memory T-cells to prolong tumor rejection. While traditional as well as modern vaccines rely upon delivery of both antigen and adjuvant, a variety of clinically relevant cancers lack ideal immunogenic antigens. Building upon recent efforts, we instead chose to exploit chemotherapy-induced apoptosis to allow for antigen generation in a combination, nanomedicine-based approach. Specifically, lipid-coated cisplatin nanoparticles (LPC) and CpG-encapsulated liposomes (CpG-Lipo) were prepared for the temporally-controlled and multifaceted treatment of an advanced model of melanoma. Such combination therapy established strong synergistic effects, both in apoptotic extent and subsequent abrogation of tumor growth, which were due largely to both an enhanced cytotoxic T-cell recruitment and a reduction of immune-suppressive mediators in the microenvironments of both spleens and tumor. These results underlie a prolonged host lifespan in the combination approach (45 days) as compared with control (25 days, p < 0.02), providing promise toward a personalized approach to nanomedicine by establishing effect synergy in host-specific immunotherapy following chemotherapy.
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