2016
DOI: 10.18632/oncotarget.8095
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MRP1-CD28 bi-specific oligonucleotide aptamers: target costimulation to drug-resistant melanoma cancer stem cells

Abstract: In this work we show a clinically feasible strategy to convert in situ the own tumor into an endogenous vaccine by coating the melanoma cancerous cells with CD28 costimulatory ligands. This therapeutic approach is aimed at targeting T-cell costimulation to chemotherapy-resistant tumors which are refractory and been considered as untreatable cancers. These tumors are usually defined by an enrichment of cancer stem cells and characterized by the higher expression of chemotherapy-resistant proteins. In this work … Show more

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Cited by 58 publications
(57 citation statements)
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“…As shown in their previous study, dimeric CD28 aptamers were able to trigger a strong co-stimulation signal in antigen-specific T lymphocytes 16 . They engineered an MRP1-CD28 bivalent aptamer that was able to bind MRP1-expressing tumors and deliver the CD28 co-stimulatory signal to tumor-infiltrating lymphocytes 38 . Multidrug-resistant-associated protein 1 (MRP1) has been directly correlated with chemotherapy drug resistance in several types of tumors 39 .…”
Section: Main Textmentioning
confidence: 91%
See 1 more Smart Citation
“…As shown in their previous study, dimeric CD28 aptamers were able to trigger a strong co-stimulation signal in antigen-specific T lymphocytes 16 . They engineered an MRP1-CD28 bivalent aptamer that was able to bind MRP1-expressing tumors and deliver the CD28 co-stimulatory signal to tumor-infiltrating lymphocytes 38 . Multidrug-resistant-associated protein 1 (MRP1) has been directly correlated with chemotherapy drug resistance in several types of tumors 39 .…”
Section: Main Textmentioning
confidence: 91%
“…In the third study, Pastor’s group constructed a bi-specific aptamer to coat melanoma cancer cells with stimulatory signals for T cells 38 . As shown in their previous study, dimeric CD28 aptamers were able to trigger a strong co-stimulation signal in antigen-specific T lymphocytes 16 .…”
Section: Main Textmentioning
confidence: 94%
“…We have recently published a bi-specific CD28-MRP1 aptamer to target CD28 co-stimulation to cancer stem cells (represented in Figure 4c) [89]. The targeted co-stimulation to cancer stem cells which imply chemotherapy resistance would exert a selection pressure on these cells usually responsible for tumor metastasis and tumor relapses [79,90].…”
Section: Bi-specific Aptamers To Target the Immune Response To The Tumentioning
confidence: 99%
“…This targeting approach showed a better therapeutic index than the non-targeting 4-1BB agonistic antibody. We have also recently developed a bi-specific aptamer to target CD28 co-stimulatory aptamers to tumors that overexpressed MRP1, which is a chemotherapy-resistant channel up-regulated in cancer stem cells, cells with higher resistance to chemotherapy [66]. Similar strategies could also be used to target immune-checkpoint blockade aptamers (CTLA4, PD1, TIM3, etc.)…”
Section: Immunostimulatory Aptamersmentioning
confidence: 99%
“…However, translation to the clinic is technically challenging, as an autologous genetically-modified tumor cell line for each patient needs to be generated [68]. The use of bi-specific co-stimulatory aptamers that are able to attach to the tumor cell surface would significantly simplify the generation of this type of vaccine; we have coined the term AptVax as the vaccine of tumor-irradiated cells coated with co-stimulatory bi-specific aptamers [66]. …”
Section: Immunostimulatory Aptamersmentioning
confidence: 99%