Shaping the "hot" immunogenic tumor microenvironment by nanoparticles co-delivering oncolytic peptide and TGF-β1 siRNA for boosting checkpoint blockade therapy.

Phung CD, Nguyen BL, Jeong JH, Chang JH, Jin SG, Choi HG, Ku SK, Kim JO

Bioengineering & translational medicine11 Aug 2022Cited by 16 (Europe PMC)

PMID37693065PMCIDPMC10487304DOI10.1002/btm2.10392PepBankPUB-37693065

Summary

Induction of potent immune responses toward tumors remains challenging in cancer immunotherapy, in which it only showed benefits in a minority of patients with "hot" tumors, which possess pre-existing effector immune cells within the tumor. In this study, we proposed a nanoparticle-based strategy to fire up the "cold" tumor by upregulating the components associated with T and NK cell recruitment and activation and suppressing TGF-β1 secretion by tumor cells. Specifically, LTX-315, a first-in-class oncolytic cationic peptide, and TGF-β1 siRNA were co-entrapped in a polymer-lipid hybrid nanoparticle comprising PLGA, DSPE-mPEG, and DSPE-PEG-conjugated with cRGD peptide (LTX/siR-NPs). The LTX/siR-NPs showed significant inhibition of TGF-β1 expression, induction of type I interferon release, and triggering immunogenic cell death (ICD) in treated tumor cells, indicated via the increased levels of danger molecules, an in vitro setting. The in vivo data showed that the LTX/siR-NPs could effectively protect the LTX-315 peptide from degradation in serum, which highly accumulated in tumor tissue. Consequently, the LTX/siR-NPs robustly suppressed TGF-β1 production by tumor cells and created an immunologically active tumor with high infiltration of antitumor effector immune cells. As a result, the combination of LTX/siR-NP treatment with NKG2A checkpoint inhibitor therapy remarkably increased numbers of CD8⁺NKG2D⁺ and NK1.1⁺NKG2D⁺ within tumor masses, and importantly, inhibited the tumor growth and prolonged survival rate of treated mice. Taken together, this study suggests the potential of the LTX/siR-NPs for inflaming the "cold" tumor for potentiating the efficacy of cancer immunotherapy.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study12

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone12

In this study, LTX-315 was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking LTX-315.

01AnimalNot a test of LTX-315 aloneAnimal study (in vivo)Pharmacokinetics
In vivo, LTX/siR-NPs protected LTX‑315 from serum degradation.
In plain wordsIn animals, the LTX‑315 and siRNA nanoparticles protected the peptide from breakdown in serum.
Peptide
LTX-315
Outcome
DecreaseSerum degradation
Study
n: not reported in source
Outcome group
Pharmacokinetics · Cancer
Source sentences
Summary
The in vivo data showed that the LTX/siR-NPs could effectively protect the LTX-315 peptide from degradation in serum, which highly accumulated in tumor tissue.
1 context sentence(design, population, supporting numbers)
Summary · context
Specifically, LTX-315, a first-in-class oncolytic cationic peptide, and TGF-β1 siRNA were co-entrapped in a polymer-lipid hybrid nanoparticle comprising PLGA, DSPE-mPEG, and DSPE-PEG-conjugated with cRGD peptide (LTX/siR-NPs).
In this study, LTX-315 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking LTX-315.
Show in the study text Report a problemFND-3769306505
02AnimalNot a test of LTX-315 aloneAnimal study (in vivo)Pharmacokinetics
In vivo, LTX/siR-NPs showed high tumor tissue accumulation.
In plain wordsIn animals, the LTX‑315 and siRNA nanoparticles accumulated in tumor tissue.
Peptide
LTX-315
Outcome
Direction not reportedTumor accumulation
Study
n: not reported in source
Outcome group
Pharmacokinetics · Cancer
Source sentences
Summary
The in vivo data showed that the LTX/siR-NPs could effectively protect the LTX-315 peptide from degradation in serum, which highly accumulated in tumor tissue.
1 context sentence(design, population, supporting numbers)
Summary · context
Specifically, LTX-315, a first-in-class oncolytic cationic peptide, and TGF-β1 siRNA were co-entrapped in a polymer-lipid hybrid nanoparticle comprising PLGA, DSPE-mPEG, and DSPE-PEG-conjugated with cRGD peptide (LTX/siR-NPs).
In this study, LTX-315 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking LTX-315.
Show in the study text Report a problemFND-3769306506
03AnimalNot a test of LTX-315 aloneAnimal study (in vivo)Mechanism
In tumors, LTX/siR-NPs suppressed TGF-β1 production.
In plain wordsIn animals, the LTX‑315 and siRNA nanoparticles reduced tumor TGF-β1 production.
Peptide
LTX-315
Outcome
DecreaseTumor TGF-β1 production
Study
n: not reported in source
Outcome group
Receptor activity and mechanism · Cancer
Source sentences
Summary
Consequently, the LTX/siR-NPs robustly suppressed TGF-β1 production by tumor cells and created an immunologically active tumor with high infiltration of antitumor effector immune cells.
1 context sentence(design, population, supporting numbers)
Summary · context
Specifically, LTX-315, a first-in-class oncolytic cationic peptide, and TGF-β1 siRNA were co-entrapped in a polymer-lipid hybrid nanoparticle comprising PLGA, DSPE-mPEG, and DSPE-PEG-conjugated with cRGD peptide (LTX/siR-NPs).
In this study, LTX-315 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking LTX-315.
Show in the study text Report a problemFND-3769306507
04AnimalNot a test of LTX-315 aloneAnimal study (in vivo)Mechanism
In tumors, LTX/siR-NPs produced high antitumor effector immune cell infiltration.
In plain wordsIn animals, the LTX‑315 and siRNA nanoparticles produced high immune cell infiltration into tumors.
Peptide
LTX-315
Outcome
IncreaseEffector immune cell infiltration
Study
n: not reported in source
Outcome group
Immune response · Cancer
Source sentences
Summary
Consequently, the LTX/siR-NPs robustly suppressed TGF-β1 production by tumor cells and created an immunologically active tumor with high infiltration of antitumor effector immune cells.
1 context sentence(design, population, supporting numbers)
Summary · context
Specifically, LTX-315, a first-in-class oncolytic cationic peptide, and TGF-β1 siRNA were co-entrapped in a polymer-lipid hybrid nanoparticle comprising PLGA, DSPE-mPEG, and DSPE-PEG-conjugated with cRGD peptide (LTX/siR-NPs).
In this study, LTX-315 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking LTX-315.
Show in the study text Report a problemFND-3769306508
05AnimalNot a test of LTX-315 aloneAnimal study (in vivo)Mechanism
In mice, LTX/siR-NPs with NKG2A checkpoint inhibition increased intratumoral CD8+NKG2D+ cells.
In plain wordsIn mice, the nanoparticle and checkpoint inhibitor combination increased CD8+NKG2D+ cells in tumors.
Peptide
LTX-315
Outcome
IncreaseCD8+NKG2D+ cells
Study
mousen: not reported in source
Outcome group
Immune response · Cancer
Source sentences
Summary
As a result, the combination of LTX/siR-NP treatment with NKG2A checkpoint inhibitor therapy remarkably increased numbers of CD8⁺NKG2D⁺ and NK1.1⁺NKG2D⁺ within tumor masses, and importantly, inhibited the tumor growth and prolonged survival rate of treated mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Specifically, LTX-315, a first-in-class oncolytic cationic peptide, and TGF-β1 siRNA were co-entrapped in a polymer-lipid hybrid nanoparticle comprising PLGA, DSPE-mPEG, and DSPE-PEG-conjugated with cRGD peptide (LTX/siR-NPs).
In this study, LTX-315 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking LTX-315.
Show in the study text Report a problemFND-3769306509
06AnimalNot a test of LTX-315 aloneAnimal study (in vivo)Mechanism
In mice, LTX/siR-NPs with NKG2A checkpoint inhibition increased intratumoral NK1.1+NKG2D+ cells.
In plain wordsIn mice, the nanoparticle and checkpoint inhibitor combination increased NK1.1+NKG2D+ cells in tumors.
Peptide
LTX-315
Outcome
IncreaseNK1.1+NKG2D+ cells
Study
mousen: not reported in source
Outcome group
Immune response · Cancer
Source sentences
Summary
As a result, the combination of LTX/siR-NP treatment with NKG2A checkpoint inhibitor therapy remarkably increased numbers of CD8⁺NKG2D⁺ and NK1.1⁺NKG2D⁺ within tumor masses, and importantly, inhibited the tumor growth and prolonged survival rate of treated mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Specifically, LTX-315, a first-in-class oncolytic cationic peptide, and TGF-β1 siRNA were co-entrapped in a polymer-lipid hybrid nanoparticle comprising PLGA, DSPE-mPEG, and DSPE-PEG-conjugated with cRGD peptide (LTX/siR-NPs).
In this study, LTX-315 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking LTX-315.
Show in the study text Report a problemFND-3769306510
07AnimalNot a test of LTX-315 aloneAnimal study (in vivo)Efficacy outcome
In mice, LTX/siR-NPs with NKG2A checkpoint inhibition inhibited tumor growth.
In plain wordsIn mice, the nanoparticle and checkpoint inhibitor combination inhibited tumor growth.
Peptide
LTX-315
Outcome
DecreaseTumor growth
Study
mousen: not reported in source
Outcome group
Tumor growth · Cancer
Source sentences
Summary
As a result, the combination of LTX/siR-NP treatment with NKG2A checkpoint inhibitor therapy remarkably increased numbers of CD8⁺NKG2D⁺ and NK1.1⁺NKG2D⁺ within tumor masses, and importantly, inhibited the tumor growth and prolonged survival rate of treated mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Specifically, LTX-315, a first-in-class oncolytic cationic peptide, and TGF-β1 siRNA were co-entrapped in a polymer-lipid hybrid nanoparticle comprising PLGA, DSPE-mPEG, and DSPE-PEG-conjugated with cRGD peptide (LTX/siR-NPs).
In this study, LTX-315 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking LTX-315.
Show in the study text Report a problemFND-3769306511
08AnimalNot a test of LTX-315 aloneAnimal study (in vivo)Efficacy outcome
In mice, LTX/siR-NPs with NKG2A checkpoint inhibition prolonged survival.
In plain wordsIn mice, the nanoparticle and checkpoint inhibitor combination prolonged survival.
Peptide
LTX-315
Outcome
IncreaseSurvival
Study
mousen: not reported in source
Outcome group
Mortality · Cancer
Source sentences
Summary
As a result, the combination of LTX/siR-NP treatment with NKG2A checkpoint inhibitor therapy remarkably increased numbers of CD8⁺NKG2D⁺ and NK1.1⁺NKG2D⁺ within tumor masses, and importantly, inhibited the tumor growth and prolonged survival rate of treated mice.
1 context sentence(design, population, supporting numbers)
Summary · context
Specifically, LTX-315, a first-in-class oncolytic cationic peptide, and TGF-β1 siRNA were co-entrapped in a polymer-lipid hybrid nanoparticle comprising PLGA, DSPE-mPEG, and DSPE-PEG-conjugated with cRGD peptide (LTX/siR-NPs).
In this study, LTX-315 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking LTX-315.
Show in the study text Report a problemFND-3769306512
09LabNot a test of LTX-315 aloneIn vitro (cells)Mechanism
In tumor cells, LTX/siR-NPs inhibited TGF-β1 expression.
In plain wordsIn cells, the LTX‑315 and siRNA nanoparticles reduced TGF-β1 expression.
Peptide
LTX-315
Outcome
DecreaseTGF-β1 expression
Study
n: not reported in source
Outcome group
Receptor activity and mechanism · Cancer
Source sentences
Summary
The LTX/siR-NPs showed significant inhibition of TGF-β1 expression, induction of type I interferon release, and triggering immunogenic cell death (ICD) in treated tumor cells, indicated via the increased levels of danger molecules, an in vitro setting.
1 context sentence(design, population, supporting numbers)
Summary · context
Specifically, LTX-315, a first-in-class oncolytic cationic peptide, and TGF-β1 siRNA were co-entrapped in a polymer-lipid hybrid nanoparticle comprising PLGA, DSPE-mPEG, and DSPE-PEG-conjugated with cRGD peptide (LTX/siR-NPs).
In this study, LTX-315 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking LTX-315.
Show in the study text Report a problemFND-3769306501
10LabNot a test of LTX-315 aloneIn vitro (cells)Mechanism
In tumor cells, LTX/siR-NPs induced type I interferon release.
In plain wordsIn cells, the LTX‑315 and siRNA nanoparticles induced type I interferon release.
Peptide
LTX-315
Outcome
IncreaseType I interferon release
Study
n: not reported in source
Outcome group
Immune response · Cancer
Source sentences
Summary
The LTX/siR-NPs showed significant inhibition of TGF-β1 expression, induction of type I interferon release, and triggering immunogenic cell death (ICD) in treated tumor cells, indicated via the increased levels of danger molecules, an in vitro setting.
1 context sentence(design, population, supporting numbers)
Summary · context
Specifically, LTX-315, a first-in-class oncolytic cationic peptide, and TGF-β1 siRNA were co-entrapped in a polymer-lipid hybrid nanoparticle comprising PLGA, DSPE-mPEG, and DSPE-PEG-conjugated with cRGD peptide (LTX/siR-NPs).
In this study, LTX-315 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking LTX-315.
Show in the study text Report a problemFND-3769306502
11LabNot a test of LTX-315 aloneIn vitro (cells)Efficacy outcome
In tumor cells, LTX/siR-NPs triggered immunogenic cell death.
In plain wordsIn cells, the LTX‑315 and siRNA nanoparticles triggered immune-related cell death.
Peptide
LTX-315
Outcome
IncreaseImmunogenic cell death
Study
n: not reported in source
Outcome group
Tumor growth · Cancer
Source sentences
Summary
The LTX/siR-NPs showed significant inhibition of TGF-β1 expression, induction of type I interferon release, and triggering immunogenic cell death (ICD) in treated tumor cells, indicated via the increased levels of danger molecules, an in vitro setting.
1 context sentence(design, population, supporting numbers)
Summary · context
Specifically, LTX-315, a first-in-class oncolytic cationic peptide, and TGF-β1 siRNA were co-entrapped in a polymer-lipid hybrid nanoparticle comprising PLGA, DSPE-mPEG, and DSPE-PEG-conjugated with cRGD peptide (LTX/siR-NPs).
In this study, LTX-315 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking LTX-315.
Show in the study text Report a problemFND-3769306503
12LabNot a test of LTX-315 aloneIn vitro (cells)Mechanism
In tumor cells, LTX/siR-NPs increased danger molecule levels.
In plain wordsIn cells, the LTX‑315 and siRNA nanoparticles increased danger molecule levels.
Peptide
LTX-315
Outcome
IncreaseDanger molecule levels
Study
n: not reported in source
Outcome group
Immune response · Cancer
Source sentences
Summary
The LTX/siR-NPs showed significant inhibition of TGF-β1 expression, induction of type I interferon release, and triggering immunogenic cell death (ICD) in treated tumor cells, indicated via the increased levels of danger molecules, an in vitro setting.
1 context sentence(design, population, supporting numbers)
Summary · context
Specifically, LTX-315, a first-in-class oncolytic cationic peptide, and TGF-β1 siRNA were co-entrapped in a polymer-lipid hybrid nanoparticle comprising PLGA, DSPE-mPEG, and DSPE-PEG-conjugated with cRGD peptide (LTX/siR-NPs).
In this study, LTX-315 was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking LTX-315.
Show in the study text Report a problemFND-3769306504

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
27 Oct 2026, 18:20 UTC
Study results updated
Version 1
27 Oct 2026, 16:32 UTC
First added · source update from Europe PMC

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Keywords

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