Potencial de los receptores Her1, Her2 y Her3 como antígenos para el desarrollo de vacunas terapéuticas contra el cáncer / Potential of Her1, Her2, and Her3 receptors as antigens for the development of therapeutic cancer vaccines

Autores/as

Palabras clave:

cáncer; inmunoterapia; receptores del factor de crecimiento epidérmico; vacunas

Resumen

Introducción: Los receptores Her1, Her2 y Her3, constituyen dianas terapéuticas valiosas en oncología debido a su sobreexpresión en múltiples carcinomas y su papel central en la proliferación y supervivencia celular. Aunque son el blanco de anticuerpos monoclonales e inhibidores de tirosina quinasa, estas terapias presentan limitaciones como la resistencia y la inmunidad transitoria.
Objetivo: Analizar el potencial de Her1, Her2 y Her3 como antígenos para el desarrollo de vacunas terapéuticas contra el cáncer.
Métodos: Se realizó una revisión sistemática de la literatura científica en PubMed, Scopus, Web of Science y Scielo comprendida entre abril y diciembre de 2025. Se seleccionaron y analizaron un total de 71 referencias que cumplieron con los criterios de selección.
Desarrollo: Las vacunas terapéuticas representan una estrategia de inmunoterapia activa que busca generar una respuesta inmunológica policlonal, duradera y dirigida contra múltiples epítopos. Para vencer la tolerancia inmunológica hacia estos antígenos propios, se destacan formulaciones que utilizan liposomas como adyuvantes. La revisión describe avances preclínicos y clínicos de vacunas basadas en Her1, Her2 y, más recientemente, en Her3, demostrando su capacidad para inducir anticuerpos policlonales que bloquean vías de señalización y reducen la viabilidad tumoral.
Conclusiones: Los receptores Her1, Her2 y Her3 se consolidan como antígenos tumorales promisorios para el desarrollo de vacunas. Su formulación en sistemas liposomales adyuvados representa una alternativa estratégica para generar respuestas inmunes policlonales, multiepítopo y de memoria, con potencial para superar algunas limitaciones de las terapias dirigidas actuales y ofrecer un efecto antitumoral sinérgico en carcinomas HER-positivos.

Descargas

Los datos de descargas todavía no están disponibles.

Citas

1. Dhomen NS, Mariadason J, Tebbutt N, Scott AM. Therapeutic Targeting of the Epidermal Growth Factor Receptor in Human Cancer. Critical Reviews in Oncogenesis. 2012;17(1):31-50. [acceso: 05/01/2026]. DOI: https://doi.org/10.1615/CritRevOncog.v17.i1.40

2. Bergado G, Hernández DR, Mazorra Z, Sánchez B. HER1-based vaccine: Simultaneous activation of humoral and cellular immune response. Seminars in Oncology. 2018;45(1-2):75-83. [acceso: 07/01/2026]. DOI: https://doi.org/10.1053/j.seminoncol.2018.05.002

3. Finn OJ. Cancer vaccines: Between the idea and the reality. Nature Reviews Immunology. 2003;3(8):630-41. [acceso: 07/01/2026]. DOI: https://doi.org/10.1038/nri1150

4. Ramírez BS, Pestana ES, Hidalgo GG, García TH, Rodríguez RP, Ullrich A, et al. Active antimetastatic immunotherapy in Lewis lung carcinoma with self EGFR extracellular domain protein in VSSP adjuvant. International Journal of Cancer. 2006;119(9):2190-9. [acceso: 02/01/2026]. DOI: https://doi.org/10.1002/ijc.22085

5. Fenoglio D, Traverso P, Parodi A, Kalli F, Zanetti M, Filaci G. Generation of more effective cancer vaccines. Human Vaccines & Immunotherapeutics. 2013;9(12):2543-7. [acceso: 04/01/2026]. DOI: https://doi.org/10.4161/hv.26147

6. Rao M, Peachman KK, Alving CR. Liposome Formulations as Adjuvants for Vaccines. Current Topics in Microbiology and Immunology. 2021;433:1-28. [acceso: 06/01/2026]. DOI: https://doi.org/10.1007/82_2020_227

7. Fan Y, Marioli M, Zhang K. Analytical characterization of liposomes and other lipid nanoparticles for drug delivery. Journal of Pharmaceutical and Biomedical Analysis. 2021;192:113642. [acceso: 09/01/2026]. DOI: https://doi.org/10.1016/j.jpba.2020.113642

8. Poria R, Kala D, Nagraik R, Dhir Y, Dhir S, Singh B, et al. Desarrollo de vacunas: Tendencias y tecnologías actuales. Life Sciences. 2024;336:122331. [acceso: 04/01/2026]. DOI: https://doi.org/10.1016/j.lfs.2023.122331

9. Saxena M, van der Burg SH, Melief CJM, Bhardwaj N. Vacunas terapéuticas contra el cáncer. Nature Reviews Cancer. 2021;21(6):360-78. [acceso: 05/01/2026]. DOI: https://doi.org/10.1038/s41568-021-00346-0

10. Bastola R, Noh G, Keum T, Bashyal S, Seo JE, Choi J, et al. Vaccine adjuvants: Smart components to boost the immune system. Archives of Pharmacal Research. 2017;40(11):1238-48. [acceso: 05/01/2026]. DOI: https://doi.org/10.1007/s12272-017-0969-z

11. Luo L, Luo Z, Wang L, Hu Y, Zhang J, Yin H, et al. Liposome Vaccine for Active Regulation of Cellular and Humoral Immunity. Molecular Pharmaceutics. 2023;20(11):5668-81. [acceso: 05/01/2026]. DOI: https://doi.org/10.1021/acs.molpharmaceut.3c00536

12. Krasnopolsky Y, Pylypenko D. Licensed liposomal vaccines and adjuvants in the antigen delivery system. Biotechnologia. 2022;103(4):359-72. [acceso: 05/01/2026]. DOI: https://doi.org/10.5114/bta.2022.120709

13. Ullrich A, Coussens L, Hayflick JS, Dull TJ, Gray A, Tam AW, et al. Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. Nature. 1984;309(5967):418-25. [acceso: 08/01/2026]. DOI: https://doi.org/10.1038/309418a0

14. Gao L, Zhang Y, Feng M, Shen M, Yang L, Wei B, et al. HER3: Updates and current biology function, targeted therapy and pathologic detecting methods. Life Sciences. 2024;357:123087. [acceso: 07/01/2026]. DOI: https://doi.org/10.1016/j.lfs.2024.123087

15. Bermudez-Abreut E, Bergado-Báez G, Fundora-Barrios T, Arencibia-Perezleo J, Lopez Medinilla A, Chao L, et al. HER1 (EGFR) and/or HER2 Inclusion Potentiates the Antitumor Effect Elicited by a HER3-Specific Monovalent Vaccine. Molecular Cancer Therapeutics. 2025;24(8):1226-39. [acceso: 09/01/2026]. DOI: https://doi.org/10.1158/1535-7163.MCT-24-0973

16. Halder S, Basu S, Lall SP, Ganti AK, Batra SK, Seshacharyulu P. Targeting the EGFR signaling pathway in cancer therapy: What's new in 2023? Expert Opinion on Therapeutic Targets. 2023;27(4-5):305-24. [acceso: 05/01/2026]. DOI: https://doi.org/10.1080/14728222.2023.2218613

17. Cai X, Zhang L, Chen S. Editorial: Cancer Treatment and Early Detection Targeting HER Receptors. Frontiers in Molecular Biosciences. 2022;9:940055. [acceso: 05/01/2026]. DOI: https://doi.org/10.3389/fmolb.2022.940055

18. Nair S, Bonner JA, Bredel M. EGFR Mutations in Head and Neck Squamous Cell Carcinoma. International Journal of Molecular Sciences. 2022;23(7):3818. [acceso: 02/01/2026]. DOI: https://doi.org/10.3390/ijms23073818

19. Nowak J, Bentele M, Kutle I, Zimmermann K, Lühmann JL, Steinemann D, et al. CAR-NK Cells Targeting HER1 (EGFR) Show Efficient Anti-Tumor Activity against Head and Neck Squamous Cell Carcinoma (HNSCC). Cancers. 2023;15(12):3169. [acceso: 04/01/2026]. DOI: https://doi.org/10.3390/cancers15123169

20. Cheng X. A Comprehensive Review of HER2 in Cancer Biology and Therapeutics. Genes. 2024;15(7):903. [acceso: 05/01/2026]. DOI: https://doi.org/10.3390/genes15070903

21. Nasioudis D, Gysler S, Latif N, Cory L, Giuntoli RL, Kim SH, et al. Molecular landscape of ERBB2/HER2 gene amplification among patients with gynecologic malignancies; clinical implications and future directions. Gynecologic Oncology. 2024;180:1-5. [acceso: 05/01/2026]. DOI: https://doi.org/10.1016/j.ygyno.2023.11.021

22. Pous A, Notario L, Hierro C, Layos L, Bugés C. HER2-Positive Gastric Cancer: The Role of Immunotherapy and Novel Therapeutic Strategies. International Journal of Molecular Sciences. 2023;24(14):11403. [acceso: 06/01/2026]. DOI: https://doi.org/10.3390/ijms241411403

23. Balestra A, Larsimont D, Noël JC. HER2 Amplification in p53-Mutated Endometrial Carcinomas. Cancers. 2023;15(5):1435. DOI: https://doi.org/10.3390/cancers15051435

24. Riudavets M, Sullivan I, Abdayem P, Planchard D. Targeting HER2 in non-small-cell lung cancer (NSCLC): A glimpse of hope? An updated review on therapeutic strategies in NSCLC harbouring HER2 alterations. Open is the European Society for Medical Oncology's. 2021;6(5):100260. [acceso: 05/01/2026]. DOI: https://doi.org/10.1016/j.esmoop.2021.100260

25. Ergun Y. HER3 in breast cancer: molecular insights, clinical implications, and therapeutic horizons. Expert Opinion on Therapeutic Targets. 2025;29(7):481-9. [acceso: 05/01/2026]. DOI: https://doi.org/10.1080/14728222.2025.2540355

26. Desai O, Rathore M, Boutros CS, Wright M, Bryson E, Curry K, et al. HER3: Unmasking a twist in the tale of a previously unsuccessful therapeutic pursuit targeting a key cancer survival pathway. Genes & Diseases. 2025;12(4):101354. [acceso: 07/01/2026]. DOI: https://doi.org/10.1016/j.gendis.2024.101354

27. Jenke R, Heinrich T, Lordick F, Aigner A. ERBB3 influences the ferroptosis pathway via modulation of lipid peroxidation and GSH synthesis in gastric cancer. Cell Death Discovery. 2025;11(1):398. [acceso: 08/01/2026]. DOI: https://doi.org/10.1038/s41420-025-02707-2

28. Bermúdez Abreut E, Bergado Báez G, Martínez Pestano M, Attanasio G, Gonzales Castillo CY, Hernández Fernández DR, et al. Antitumor activity of PAbs generated by immunization with a novel HER3-targeting protein-based vaccine candidate in preclinical models. Frontiers in Oncology. 2024;14:1472607. [acceso: 09/01/2026]. DOI: https://doi.org/10.3389/fonc.2024.1472607

29. Kim M, Ju HM, Song JY, Sampson J, Bayliss R, Choi J. HER3 overexpression: a predictive marker for poor prognosis in advanced ALK-positive non-small cell lung cancer treated with ALK inhibitors. Translational Lung Cancer Research. 2024;13(2):321-33. [acceso: 09/01/2026].DOI: https://doi.org/10.21037/tlcr-23-804

30. Gao L, Zhang Y, Feng M, Shen M, Yang L, Wei B, et al. HER3: Updates and current biology function, targeted therapy and pathologic detecting methods. Life Sciences. 2024;357:123087. [acceso: 08/01/2026]. DOI: https://doi.org/10.1016/j.lfs.2024.123087

31. Uribe ML, Marrocco I, Yarden Y. EGFR in Cancer: Signaling Mechanisms, Drugs, and Acquired Resistance. Cancers. 2021;13(11):2748. [acceso: 05/01/2026]. DOI: https://doi.org/10.3390/cancers13112748

32. Reichert JM. Marketed therapeutic antibodies compendium. mAbs. 2012;4(3):413-5. [acceso: 03/01/2026]. DOI: https://doi.org/10.4161/mabs.19931

33. Ramos M, Lorenzo P, Lazo NG, Perez ML, Soriano JL, Gonzalez CEV, et al. Treatment of malignant, non-resectable, epithelial origin esophageal tumours with the humanized anti-epidermal growth factor antibody nimotuzumab combined with radiation therapy and chemotherapy. Cancer Biology & Therapy. 2012;13(8):600-5. [acceso: 03/01/2026]. DOI: https://doi.org/10.4161/cbt.19849

34. Najjar MK, Manore SG, Regua AT, Lo HW. Antibody-Drug Conjugates for the Treatment of HER2-Positive Breast Cancer. Genes. 2022;13(11):2065. [acceso: 05/01/2026]. DOI: https://doi.org/10.3390/genes13112065

35. Rugo HS, Im SA, Cardoso F, Cortés J, Curigliano G, Musolino A, et al. Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncology. 2021;7(4):573-84. [acceso: 05/01/2026]. DOI: https://doi.org/10.1001/jamaoncol.2020.7932

36. Desai O, Rathore M, Boutros CS, Wright M, Bryson E, Curry K, et al. HER3: Unmasking a twist in the tale of a previously unsuccessful therapeutic pursuit targeting a key cancer survival pathway. Genes & Diseases. 2025;12(4):101354. [acceso: 05/01/2026]. DOI: https://doi.org/10.1016/j.gendis.2024.101354

37. Gandullo Sánchez L, Ocaña A, Pandiella A. HER3 in cancer: from the bench to the bedside. Journal of Experimental & Clinical Cancer Research. 2022;41(1):310. [acceso: 05/01/2026]. D DOI: https://doi.org/10.1186/s13046-022-02515-x

38. Jänne PA, Baik C, Su WC, Johnson ML, Hayashi H, Nishio M, et al. Efficacy and Safety of Patritumab Deruxtecan (HER3-DXd) in EGFR Inhibitor-Resistant, EGFR-Mutated Non-Small Cell Lung Cancer. Cancer Discovery. 2022;12(1):74-89. [acceso: 05/01/2026]. DOI: https://doi.org/10.1158/2159-8290.CD-21-0715

39. Yu HA, Goto K, Kim DW, Su WC, Yang JC, Morgenstern D, et al. HERTHENA-Lung01, a Phase II Trial of Patritumab Deruxtecan (HER3-DXd) in Epidermal Growth Factor Receptor-Mutated Non-Small-Cell Lung Cancer After Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Platinum-Based Chemotherapy. Journal of Clinical Oncology. 2023;41(36):5363-75. [acceso: 05/01/2026]. DOI: https://doi.org/10.1200/JCO.23.01476

40. Schram AM, Goto K, Kim DW, Macarulla T, Hollebecque A, O'Reilly EM, et al. Zenocutuzumab in NRG1 Fusion-Positive Advanced Solid Tumors: Efficacy and Safety from the Phase 1/2 eNRGy Trial. New England Journal of Medicine. 2025;392(6):566-76. [acceso: 05/01/2026]. DOI: https://doi.org/10.1056/NEJMoa2405008

41. Liu J, Fu M, Wang M, Wan D, Wei Y, Wei X. Cancer vaccines as promising immuno-therapeutics: Platforms and current progress. Journal of Hematology and Oncology. 2022;15(1):28. [acceso: 05/01/2026]. DOI: https://doi.org/10.1186/s13045-022-01247-x

42. Milani A, Sangiolo D, Montemurro F, Aglietta M, Valabrega G. Active immunotherapy in HER2 overexpressing breast cancer: Current status and future perspectives. Annals of Oncology. 2013;24(7):1740-8. [acceso: 05/01/2026]. DOI: https://doi.org/10.1093/annonc/mdt133

43. Murray JL, Gillogly ME, Przepiorka D, Brewer H, Ibrahim NK, Booser DJ, et al. Toxicity, immunogenicity, and induction of E75-specific tumor-lytic CTLs by HER-2 peptide E75 (369-377) combined with granulocyte macrophage colony-stimulating factor in HLA-A2+ patients with metastatic breast and ovarian cancer. Clinical Cancer Research. 2002;8(11):3407-18. [acceso: 05/01/2026]. PMID: 12429628. Disponible en: https://pubmed.ncbi.nlm.nih.gov/12429628/.

44. Disis ML, Schiffman K, Guthrie K, Salazar LG, Knutson KL, Goodell V, et al. Effect of dose on immune response in patients vaccinated with an her-2/neu intracellular domain protein-based vaccine. Journal of Clinical Oncology. 2004;22(10):1916-25. [acceso: 05/01/2026]. DOI: https://doi.org/10.1200/JCO.2004.09.005

Descargas

Publicado

2026-05-02

Cómo citar

1.
Acosta Castro Y, Castillo Llanes J, Luzardo Lorenzo M del C. Potencial de los receptores Her1, Her2 y Her3 como antígenos para el desarrollo de vacunas terapéuticas contra el cáncer / Potential of Her1, Her2, and Her3 receptors as antigens for the development of therapeutic cancer vaccines. Arch Hosp Univ "Gen Calixto García” [Internet]. 2 de mayo de 2026 [citado 3 de mayo de 2026];14(1). Disponible en: https://revcalixto.sld.cu/index.php/ahcg/article/view/1677

Número

Sección

Artículos de Revisión