Oncolytic peptide LTX-315 plus an anti-CTLA-4 antibody induces a synergistic anti-cancer immune response in residual tumors after radiofrequency ablation of hepatocellular carcinoma.

Sun B, Liu J, Liu X, Li J, Zhang G, Sun T, Zheng C, Kan X

Cell death & disease13 Apr 2025Cited by 9 (Europe PMC)

PMID40222972PMCIDPMC11994779DOI10.1038/s41419-025-07622-zPepBankPUB-40222972

Summary

Preventing tumor recurrence after radiofrequency ablation (RFA) of malignant solid tumors with large size or in high-risk locations represents a great challenge. In this study, we explored the feasibility of using oncolytic peptide LTX-315 plus an anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody for inhibiting residual tumors after RFA of hepatocellular carcinoma (HCC). In in vitro experiment, the CD8⁺T cells from Hepa1-6 tumors, after being subjected to three different treatments (control, iRFA, iRFA + LTX-315), were extracted and were then co-cultured with Hepa1-6 cells and an anti-CTLA-4 antibody. The enzyme-linked immunospot, flow cytometry, and cell counting kit-8 assay were employed to assess the cytotoxicity of extracted CD8⁺T cells on Hepa1-6 cells. In in vivo experiment, different murine orthotopic HCC models were variously treated by: (1) pseudo iRFA + phosphate-buffered saline (PBS); (2) iRFA + PBS; (3) iRFA + LTX-315; (4) iRFA + anti-CTLA-4 antibody; and (5) iRFA + LTX-315 + anti-CTLA-4 antibody. The treatment effects were compared among different groups and were pathologically confirmed. The possible mechanisms of the combination treatment (LTX-315+anti-CTLA-4 antibody) for residual tumors after iRFA of HCC were explored. LTX-315 significantly reduced the PD-1 expression and significantly increased CTLA-4 expression of CD8⁺T cells in residual tumors, and additional treatment of anti-CTLA-4 antibody could significantly enhance the cytotoxicity of CD8⁺T cells for Hepa1-6 cells in vitro experiments. Compared with the other treatments, the combined treatment of LTX-315 with anti-CTLA-4 antibody achieved a better tumor response and longer survival, and it could synergistically activate the cGAS-STING pathway and elicit an immunogenic cell death, leading to a strong anti-tumor immunity after iRFA of HCC. The immunosuppressive microenvironment of residual tumors was significantly improved by the combination therapy with a significantly increased ratio of M1-like tumor-associated macrophages to M2-like tumor-associated macrophages, a significantly decreased infiltration of regulatory T cells and myeloid-derived suppressor cells, and a significantly lower expression of PD-1 and CTLA-4. Overall, the results of this study demonstrated that LTX-315 plus anti-CTLA-4 antibody could synergistically improve the immunosuppressive microenvironment of residual tumors and induce a strong anti-tumor immunity after iRFA of HCC. This combination treatment strategy may offer a new alternative to reduce the tumor recurrence after RFA of malignant solid tumors with large sizes or in high-risk locations.

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

Results from this study12

2 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Mechanism
In residual hepatocellular tumors, LTX‑315 significantly reduced PD-1 expression on CD8 T cells.
In plain wordsIn mice, LTX‑315 reduced PD-1 expression on immune cells in residual liver tumors.
Peptide
LTX-315
Outcome
DecreasePD-1 expression on CD8 T cells
Study
Mousen: not reported in source
Orthotopic hepatocellular carcinoma after incomplete radiofrequency ablation
Outcome group
Immune response · Cancer
Studied dose
Dose not stated
Source sentences
Summary
LTX-315 significantly reduced the PD-1 expression and significantly increased CTLA-4 expression of CD8⁺T cells in residual tumors
1 context sentence(design, population, supporting numbers)
Summary · context
In in vivo experiment, different murine orthotopic HCC models were variously treated by: (1) pseudo iRFA + phosphate-buffered saline (PBS); (2) iRFA + PBS; (3) iRFA + LTX-315; (4) iRFA + anti-CTLA-4 antibody; and (5) iRFA + LTX-315 + anti-CTLA-4 antibody.
Show in the study text Report a problemFND-4022297201
02AnimalAnimal study (in vivo)Mechanism
In residual hepatocellular tumors, LTX‑315 significantly increased CTLA-4 expression on CD8 T cells.
In plain wordsIn mice, LTX‑315 increased CTLA-4 expression on immune cells in residual liver tumors.
Peptide
LTX-315
Outcome
IncreaseCTLA-4 expression on CD8 T cells
Study
Mousen: not reported in source
Orthotopic hepatocellular carcinoma after incomplete radiofrequency ablation
Outcome group
Immune response · Cancer
Studied dose
Dose not stated
Source sentences
Summary
LTX-315 significantly reduced the PD-1 expression and significantly increased CTLA-4 expression of CD8⁺T cells in residual tumors
1 context sentence(design, population, supporting numbers)
Summary · context
In in vivo experiment, different murine orthotopic HCC models were variously treated by: (1) pseudo iRFA + phosphate-buffered saline (PBS); (2) iRFA + PBS; (3) iRFA + LTX-315; (4) iRFA + anti-CTLA-4 antibody; and (5) iRFA + LTX-315 + anti-CTLA-4 antibody.
Show in the study text Report a problemFND-4022297202

Studies that did not test the peptide alone10

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.

03AnimalNot a test of LTX-315 aloneAnimal study (in vivo)Efficacy outcome
In mice after incomplete ablation, LTX‑315 plus anti-CTLA-4 antibody achieved a better tumor response than other treatments.
In plain wordsIn mice, LTX‑315 plus antibody improved tumor response compared with other treatments after incomplete ablation.
Peptide
LTX-315
Outcome
IncreaseTumor response
Study
Mousen: not reported in source
Orthotopic hepatocellular carcinoma after incomplete radiofrequency ablation
Comparator
Other treatments
Outcome group
Tumor growth · Cancer
Source sentences
Summary
Compared with the other treatments, the combined treatment of LTX-315 with anti-CTLA-4 antibody achieved a better tumor response and longer survival, and it could synergistically activate the cGAS-STING pathway and elicit an immunogenic cell death, leading to a strong anti-tumor immunity after iRFA of HCC.
1 context sentence(design, population, supporting numbers)
Summary · context
In in vivo experiment, different murine orthotopic HCC models were variously treated by: (1) pseudo iRFA + phosphate-buffered saline (PBS); (2) iRFA + PBS; (3) iRFA + LTX-315; (4) iRFA + anti-CTLA-4 antibody; and (5) iRFA + LTX-315 + anti-CTLA-4 antibody.
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-4022297203
04AnimalNot a test of LTX-315 aloneAnimal study (in vivo)Efficacy outcome
In mice after incomplete ablation, LTX‑315 plus anti-CTLA-4 antibody prolonged survival compared with other treatments.
In plain wordsIn mice, LTX‑315 plus antibody prolonged survival compared with other treatments after incomplete ablation.
Peptide
LTX-315
Outcome
IncreaseSurvival
Study
Mousen: not reported in source
Orthotopic hepatocellular carcinoma after incomplete radiofrequency ablation
Comparator
Other treatments
Outcome group
Mortality · Cancer
Source sentences
Summary
Compared with the other treatments, the combined treatment of LTX-315 with anti-CTLA-4 antibody achieved a better tumor response and longer survival, and it could synergistically activate the cGAS-STING pathway and elicit an immunogenic cell death, leading to a strong anti-tumor immunity after iRFA of HCC.
1 context sentence(design, population, supporting numbers)
Summary · context
In in vivo experiment, different murine orthotopic HCC models were variously treated by: (1) pseudo iRFA + phosphate-buffered saline (PBS); (2) iRFA + PBS; (3) iRFA + LTX-315; (4) iRFA + anti-CTLA-4 antibody; and (5) iRFA + LTX-315 + anti-CTLA-4 antibody.
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-4022297204
05AnimalNot a test of LTX-315 aloneAnimal study (in vivo)Mechanism
In mice after incomplete ablation, LTX‑315 plus anti-CTLA-4 antibody synergistically activated the cGAS-STING pathway.
In plain wordsIn mice, LTX‑315 plus antibody activated an immune signaling pathway after incomplete tumor ablation.
Peptide
LTX-315
Outcome
IncreasecGAS-STING activation
Study
Mousen: not reported in source
Orthotopic hepatocellular carcinoma after incomplete radiofrequency ablation
Outcome group
Immune response · Cancer
Source sentences
Summary
Compared with the other treatments, the combined treatment of LTX-315 with anti-CTLA-4 antibody achieved a better tumor response and longer survival, and it could synergistically activate the cGAS-STING pathway and elicit an immunogenic cell death, leading to a strong anti-tumor immunity after iRFA of HCC.
1 context sentence(design, population, supporting numbers)
Summary · context
In in vivo experiment, different murine orthotopic HCC models were variously treated by: (1) pseudo iRFA + phosphate-buffered saline (PBS); (2) iRFA + PBS; (3) iRFA + LTX-315; (4) iRFA + anti-CTLA-4 antibody; and (5) iRFA + LTX-315 + anti-CTLA-4 antibody.
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-4022297205
06AnimalNot a test of LTX-315 aloneAnimal study (in vivo)Mechanism
In mice after incomplete ablation, LTX‑315 plus anti-CTLA-4 antibody elicited immunogenic cell death.
In plain wordsIn mice, LTX‑315 plus antibody triggered tumor cell death that stimulates immunity.
Peptide
LTX-315
Outcome
IncreaseImmunogenic cell death
Study
Mousen: not reported in source
Orthotopic hepatocellular carcinoma after incomplete radiofrequency ablation
Outcome group
Immune response · Cancer
Source sentences
Summary
Compared with the other treatments, the combined treatment of LTX-315 with anti-CTLA-4 antibody achieved a better tumor response and longer survival, and it could synergistically activate the cGAS-STING pathway and elicit an immunogenic cell death, leading to a strong anti-tumor immunity after iRFA of HCC.
1 context sentence(design, population, supporting numbers)
Summary · context
In in vivo experiment, different murine orthotopic HCC models were variously treated by: (1) pseudo iRFA + phosphate-buffered saline (PBS); (2) iRFA + PBS; (3) iRFA + LTX-315; (4) iRFA + anti-CTLA-4 antibody; and (5) iRFA + LTX-315 + anti-CTLA-4 antibody.
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-4022297206
07AnimalNot a test of LTX-315 aloneAnimal study (in vivo)Mechanism
In mice after incomplete ablation, LTX‑315 plus anti-CTLA-4 antibody elicited strong antitumor immunity.
In plain wordsIn mice, LTX‑315 plus antibody stimulated antitumor immunity after incomplete ablation.
Peptide
LTX-315
Outcome
IncreaseAntitumor immunity
Study
Mousen: not reported in source
Orthotopic hepatocellular carcinoma after incomplete radiofrequency ablation
Outcome group
Immune response · Cancer
Source sentences
Summary
Compared with the other treatments, the combined treatment of LTX-315 with anti-CTLA-4 antibody achieved a better tumor response and longer survival, and it could synergistically activate the cGAS-STING pathway and elicit an immunogenic cell death, leading to a strong anti-tumor immunity after iRFA of HCC.
1 context sentence(design, population, supporting numbers)
Summary · context
In in vivo experiment, different murine orthotopic HCC models were variously treated by: (1) pseudo iRFA + phosphate-buffered saline (PBS); (2) iRFA + PBS; (3) iRFA + LTX-315; (4) iRFA + anti-CTLA-4 antibody; and (5) iRFA + LTX-315 + anti-CTLA-4 antibody.
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-4022297207
08AnimalNot a test of LTX-315 aloneAnimal study (in vivo)Mechanism
In residual mouse tumors, LTX‑315 plus anti-CTLA-4 antibody significantly increased the M1-like to M2-like macrophage ratio.
In plain wordsIn mice, LTX‑315 plus antibody increased the ratio of M1-like to M2-like macrophages in residual tumors.
Peptide
LTX-315
Outcome
IncreaseM1-like to M2-like macrophage ratio
Study
Mousen: not reported in source
Orthotopic hepatocellular carcinoma after incomplete radiofrequency ablation
Outcome group
Immune response · Cancer
Source sentences
Summary
The immunosuppressive microenvironment of residual tumors was significantly improved by the combination therapy with a significantly increased ratio of M1-like tumor-associated macrophages to M2-like tumor-associated macrophages
1 context sentence(design, population, supporting numbers)
Summary · context
In in vivo experiment, different murine orthotopic HCC models were variously treated by: (1) pseudo iRFA + phosphate-buffered saline (PBS); (2) iRFA + PBS; (3) iRFA + LTX-315; (4) iRFA + anti-CTLA-4 antibody; and (5) iRFA + LTX-315 + anti-CTLA-4 antibody.
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-4022297208
09AnimalNot a test of LTX-315 aloneAnimal study (in vivo)Mechanism
In residual mouse tumors, LTX‑315 plus anti-CTLA-4 antibody significantly reduced regulatory T-cell infiltration.
In plain wordsIn mice, LTX‑315 plus antibody reduced regulatory T-cell infiltration in residual tumors.
Peptide
LTX-315
Outcome
DecreaseRegulatory T-cell infiltration
Study
Mousen: not reported in source
Orthotopic hepatocellular carcinoma after incomplete radiofrequency ablation
Outcome group
Immune response · Cancer
Source sentences
Summary
a significantly decreased infiltration of regulatory T cells and myeloid-derived suppressor cells, and a significantly lower expression of PD-1 and CTLA-4.
1 context sentence(design, population, supporting numbers)
Summary · context
In in vivo experiment, different murine orthotopic HCC models were variously treated by: (1) pseudo iRFA + phosphate-buffered saline (PBS); (2) iRFA + PBS; (3) iRFA + LTX-315; (4) iRFA + anti-CTLA-4 antibody; and (5) iRFA + LTX-315 + anti-CTLA-4 antibody.
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-4022297209
10AnimalNot a test of LTX-315 aloneAnimal study (in vivo)Mechanism
In residual mouse tumors, LTX‑315 plus anti-CTLA-4 antibody significantly reduced myeloid-derived suppressor cell infiltration.
In plain wordsIn mice, LTX‑315 plus antibody reduced suppressor cell infiltration in residual tumors.
Peptide
LTX-315
Outcome
DecreaseMyeloid-derived suppressor cell infiltration
Study
Mousen: not reported in source
Orthotopic hepatocellular carcinoma after incomplete radiofrequency ablation
Outcome group
Immune response · Cancer
Source sentences
Summary
a significantly decreased infiltration of regulatory T cells and myeloid-derived suppressor cells, and a significantly lower expression of PD-1 and CTLA-4.
1 context sentence(design, population, supporting numbers)
Summary · context
In in vivo experiment, different murine orthotopic HCC models were variously treated by: (1) pseudo iRFA + phosphate-buffered saline (PBS); (2) iRFA + PBS; (3) iRFA + LTX-315; (4) iRFA + anti-CTLA-4 antibody; and (5) iRFA + LTX-315 + anti-CTLA-4 antibody.
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-4022297210
11AnimalNot a test of LTX-315 aloneAnimal study (in vivo)Mechanism
In residual mouse tumors, LTX‑315 plus anti-CTLA-4 antibody significantly lowered PD-1 expression.
In plain wordsIn mice, LTX‑315 plus antibody lowered PD-1 expression in residual tumors.
Peptide
LTX-315
Outcome
DecreasePD-1 expression
Study
Mousen: not reported in source
Orthotopic hepatocellular carcinoma after incomplete radiofrequency ablation
Outcome group
Immune response · Cancer
Source sentences
Summary
a significantly decreased infiltration of regulatory T cells and myeloid-derived suppressor cells, and a significantly lower expression of PD-1 and CTLA-4.
1 context sentence(design, population, supporting numbers)
Summary · context
In in vivo experiment, different murine orthotopic HCC models were variously treated by: (1) pseudo iRFA + phosphate-buffered saline (PBS); (2) iRFA + PBS; (3) iRFA + LTX-315; (4) iRFA + anti-CTLA-4 antibody; and (5) iRFA + LTX-315 + anti-CTLA-4 antibody.
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-4022297211
12AnimalNot a test of LTX-315 aloneAnimal study (in vivo)Mechanism
In residual mouse tumors, LTX‑315 plus anti-CTLA-4 antibody significantly lowered CTLA-4 expression.
In plain wordsIn mice, LTX‑315 plus antibody lowered CTLA-4 expression in residual tumors.
Peptide
LTX-315
Outcome
DecreaseCTLA-4 expression
Study
Mousen: not reported in source
Orthotopic hepatocellular carcinoma after incomplete radiofrequency ablation
Outcome group
Immune response · Cancer
Source sentences
Summary
a significantly decreased infiltration of regulatory T cells and myeloid-derived suppressor cells, and a significantly lower expression of PD-1 and CTLA-4.
1 context sentence(design, population, supporting numbers)
Summary · context
In in vivo experiment, different murine orthotopic HCC models were variously treated by: (1) pseudo iRFA + phosphate-buffered saline (PBS); (2) iRFA + PBS; (3) iRFA + LTX-315; (4) iRFA + anti-CTLA-4 antibody; and (5) iRFA + LTX-315 + anti-CTLA-4 antibody.
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-4022297212

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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