Treatment of Advanced NSCLC Patients with an Anti-Idiotypic NeuGcGM3-Based Vaccine: Immune Correlates in Long-Term Survivors
<b>Background:</b> Racotumomab-alum is an anti-idiotype vaccine targeting the NeuGcGM3 tumor-associated ganglioside. Clinical trials in advanced cancer patients have demonstrated low toxicity, high immunogenicity and clinical benefit. The goal of this study was to identify circulating bi...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/13/5/1122 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849327546410205184 |
|---|---|
| author | Zaima Mazorra Haslen H. Cáceres-Lavernia Elia Nenínger-Vinageras Leslie M. Varona-Rodríguez Carmen Elena Viada Zuyen González Nely Rodríguez-Zhurbenko Anne-Christine Thierry Gisela María Suarez-Formigo Yendry Ventura-Carmenate Petra Baumgaertner Sara Trabanelli Camila Jandus Tania Crombet |
| author_facet | Zaima Mazorra Haslen H. Cáceres-Lavernia Elia Nenínger-Vinageras Leslie M. Varona-Rodríguez Carmen Elena Viada Zuyen González Nely Rodríguez-Zhurbenko Anne-Christine Thierry Gisela María Suarez-Formigo Yendry Ventura-Carmenate Petra Baumgaertner Sara Trabanelli Camila Jandus Tania Crombet |
| author_sort | Zaima Mazorra |
| collection | DOAJ |
| description | <b>Background:</b> Racotumomab-alum is an anti-idiotype vaccine targeting the NeuGcGM3 tumor-associated ganglioside. Clinical trials in advanced cancer patients have demonstrated low toxicity, high immunogenicity and clinical benefit. The goal of this study was to identify circulating biomarkers of clinical outcome. <b>Methods:</b> Eighteen patients with stage IIIb/IV non-small-cell lung cancer (NSCLC) were injected with racotumomab-alum as switch maintenance therapy after first-line chemotherapy. Treatment was administered until severe performance status worsening or toxicity. The frequencies of innate and adaptive lymphocytes were assessed by flow cytometry. Circulating factors were measured using multi-analyte flow assay kits. <b>Results:</b> The median overall survival was 16.5 months. Twenty-seven percent of patients were classified as long-term survivors. Patients with lower baseline frequencies of CD4+Tregs and central memory (CM) CD8+T cells displayed longer survival rates. Furthermore, higher baseline frequencies of NKT cells and a high CD8+T/CD4+Treg ratio were associated with longer survival. Interestingly, patients with significantly lower levels of effector memory (EM) CD8+T cells survived longer. The levels of NKT cells and terminal effector memory (EMRA) CD8+T cells were higher in long-term survivors in comparison with short-term survivors in post-immune samples. As expected, the ratio of CD8+T/CD4+Tregs showed significantly higher values during treatment in patients with clinical benefits. Regarding serum factors, pro-tumorigenic cytokines significantly increased during treatment in poor survivors. <b>Conclusions</b>: In advanced NSCLC patients receiving racotumomab-alum vaccine, longer survival could be associated with a unique profile of circulating lymphocyte subsets at baseline and during treatment. Additionally, certain pro-tumor-related cytokines increased in short-term survivors. These results should be confirmed in larger randomized clinical trials. This clinical trial was registered in the Cuban Clinical Trials Register (RPCE00000279). |
| format | Article |
| id | doaj-art-7fe2caa6346f4ba9b85adf9922d6e7f9 |
| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-7fe2caa6346f4ba9b85adf9922d6e7f92025-08-20T03:47:50ZengMDPI AGBiomedicines2227-90592025-05-01135112210.3390/biomedicines13051122Treatment of Advanced NSCLC Patients with an Anti-Idiotypic NeuGcGM3-Based Vaccine: Immune Correlates in Long-Term SurvivorsZaima Mazorra0Haslen H. Cáceres-Lavernia1Elia Nenínger-Vinageras2Leslie M. Varona-Rodríguez3Carmen Elena Viada4Zuyen González5Nely Rodríguez-Zhurbenko6Anne-Christine Thierry7Gisela María Suarez-Formigo8Yendry Ventura-Carmenate9Petra Baumgaertner10Sara Trabanelli11Camila Jandus12Tania Crombet13Center of Molecular Immunology, Havana 11600, CubaClinical Oncology Department, University Hospital “Hermanos Ameijeiras”, Havana 10400, CubaClinical Oncology Department, University Hospital “Hermanos Ameijeiras”, Havana 10400, CubaClinical Oncology Department, University Hospital “Hermanos Ameijeiras”, Havana 10400, CubaCenter of Molecular Immunology, Havana 11600, CubaCenter of Molecular Immunology, Havana 11600, CubaCenter of Molecular Immunology, Havana 11600, CubaCenter of Experimental Therapeutics, Department of Oncology, Lausanne University Hospital (CHUV), 1005 Lausanne, SwitzerlandDepartment of Immunology, Abu Dhabi Stem Cells Center (ADSCC), Abu Dhabi 23231, United Arab EmiratesDepartment of Immunology, Abu Dhabi Stem Cells Center (ADSCC), Abu Dhabi 23231, United Arab EmiratesCenter of Experimental Therapeutics, Department of Oncology, Lausanne University Hospital (CHUV), 1005 Lausanne, SwitzerlandDepartment of Pathology and Immunology, University of Geneva, 1211 Geneva, SwitzerlandDepartment of Pathology and Immunology, University of Geneva, 1211 Geneva, SwitzerlandCenter of Molecular Immunology, Havana 11600, Cuba<b>Background:</b> Racotumomab-alum is an anti-idiotype vaccine targeting the NeuGcGM3 tumor-associated ganglioside. Clinical trials in advanced cancer patients have demonstrated low toxicity, high immunogenicity and clinical benefit. The goal of this study was to identify circulating biomarkers of clinical outcome. <b>Methods:</b> Eighteen patients with stage IIIb/IV non-small-cell lung cancer (NSCLC) were injected with racotumomab-alum as switch maintenance therapy after first-line chemotherapy. Treatment was administered until severe performance status worsening or toxicity. The frequencies of innate and adaptive lymphocytes were assessed by flow cytometry. Circulating factors were measured using multi-analyte flow assay kits. <b>Results:</b> The median overall survival was 16.5 months. Twenty-seven percent of patients were classified as long-term survivors. Patients with lower baseline frequencies of CD4+Tregs and central memory (CM) CD8+T cells displayed longer survival rates. Furthermore, higher baseline frequencies of NKT cells and a high CD8+T/CD4+Treg ratio were associated with longer survival. Interestingly, patients with significantly lower levels of effector memory (EM) CD8+T cells survived longer. The levels of NKT cells and terminal effector memory (EMRA) CD8+T cells were higher in long-term survivors in comparison with short-term survivors in post-immune samples. As expected, the ratio of CD8+T/CD4+Tregs showed significantly higher values during treatment in patients with clinical benefits. Regarding serum factors, pro-tumorigenic cytokines significantly increased during treatment in poor survivors. <b>Conclusions</b>: In advanced NSCLC patients receiving racotumomab-alum vaccine, longer survival could be associated with a unique profile of circulating lymphocyte subsets at baseline and during treatment. Additionally, certain pro-tumor-related cytokines increased in short-term survivors. These results should be confirmed in larger randomized clinical trials. This clinical trial was registered in the Cuban Clinical Trials Register (RPCE00000279).https://www.mdpi.com/2227-9059/13/5/1122non-small cell lung canceranti-idiotypic cancer vaccinecirculating biomarkers |
| spellingShingle | Zaima Mazorra Haslen H. Cáceres-Lavernia Elia Nenínger-Vinageras Leslie M. Varona-Rodríguez Carmen Elena Viada Zuyen González Nely Rodríguez-Zhurbenko Anne-Christine Thierry Gisela María Suarez-Formigo Yendry Ventura-Carmenate Petra Baumgaertner Sara Trabanelli Camila Jandus Tania Crombet Treatment of Advanced NSCLC Patients with an Anti-Idiotypic NeuGcGM3-Based Vaccine: Immune Correlates in Long-Term Survivors Biomedicines non-small cell lung cancer anti-idiotypic cancer vaccine circulating biomarkers |
| title | Treatment of Advanced NSCLC Patients with an Anti-Idiotypic NeuGcGM3-Based Vaccine: Immune Correlates in Long-Term Survivors |
| title_full | Treatment of Advanced NSCLC Patients with an Anti-Idiotypic NeuGcGM3-Based Vaccine: Immune Correlates in Long-Term Survivors |
| title_fullStr | Treatment of Advanced NSCLC Patients with an Anti-Idiotypic NeuGcGM3-Based Vaccine: Immune Correlates in Long-Term Survivors |
| title_full_unstemmed | Treatment of Advanced NSCLC Patients with an Anti-Idiotypic NeuGcGM3-Based Vaccine: Immune Correlates in Long-Term Survivors |
| title_short | Treatment of Advanced NSCLC Patients with an Anti-Idiotypic NeuGcGM3-Based Vaccine: Immune Correlates in Long-Term Survivors |
| title_sort | treatment of advanced nsclc patients with an anti idiotypic neugcgm3 based vaccine immune correlates in long term survivors |
| topic | non-small cell lung cancer anti-idiotypic cancer vaccine circulating biomarkers |
| url | https://www.mdpi.com/2227-9059/13/5/1122 |
| work_keys_str_mv | AT zaimamazorra treatmentofadvancednsclcpatientswithanantiidiotypicneugcgm3basedvaccineimmunecorrelatesinlongtermsurvivors AT haslenhcacereslavernia treatmentofadvancednsclcpatientswithanantiidiotypicneugcgm3basedvaccineimmunecorrelatesinlongtermsurvivors AT elianeningervinageras treatmentofadvancednsclcpatientswithanantiidiotypicneugcgm3basedvaccineimmunecorrelatesinlongtermsurvivors AT lesliemvaronarodriguez treatmentofadvancednsclcpatientswithanantiidiotypicneugcgm3basedvaccineimmunecorrelatesinlongtermsurvivors AT carmenelenaviada treatmentofadvancednsclcpatientswithanantiidiotypicneugcgm3basedvaccineimmunecorrelatesinlongtermsurvivors AT zuyengonzalez treatmentofadvancednsclcpatientswithanantiidiotypicneugcgm3basedvaccineimmunecorrelatesinlongtermsurvivors AT nelyrodriguezzhurbenko treatmentofadvancednsclcpatientswithanantiidiotypicneugcgm3basedvaccineimmunecorrelatesinlongtermsurvivors AT annechristinethierry treatmentofadvancednsclcpatientswithanantiidiotypicneugcgm3basedvaccineimmunecorrelatesinlongtermsurvivors AT giselamariasuarezformigo treatmentofadvancednsclcpatientswithanantiidiotypicneugcgm3basedvaccineimmunecorrelatesinlongtermsurvivors AT yendryventuracarmenate treatmentofadvancednsclcpatientswithanantiidiotypicneugcgm3basedvaccineimmunecorrelatesinlongtermsurvivors AT petrabaumgaertner treatmentofadvancednsclcpatientswithanantiidiotypicneugcgm3basedvaccineimmunecorrelatesinlongtermsurvivors AT saratrabanelli treatmentofadvancednsclcpatientswithanantiidiotypicneugcgm3basedvaccineimmunecorrelatesinlongtermsurvivors AT camilajandus treatmentofadvancednsclcpatientswithanantiidiotypicneugcgm3basedvaccineimmunecorrelatesinlongtermsurvivors AT taniacrombet treatmentofadvancednsclcpatientswithanantiidiotypicneugcgm3basedvaccineimmunecorrelatesinlongtermsurvivors |