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Article: Dendritic Cells in Cancer Immunology and Immunotherapy.

Hato, Laura / Vizcay, Angel / Eguren, Iñaki / Pérez-Gracia, José L / Rodríguez, Javier / Gállego Pérez-Larraya, Jaime / Sarobe, Pablo / Inogés, Susana / Díaz de Cerio, Ascensión López / Santisteban, Marta

Cancers

2024 Volume 16, Issue 5

Abstract: Cancer immunotherapy modulates the immune system, overcomes immune escape and stimulates immune defenses against tumors. Dendritic cells (DCs) are professional promoters of immune responses against tumor antigens with the outstanding ability to ... ...

Abstract	Cancer immunotherapy modulates the immune system, overcomes immune escape and stimulates immune defenses against tumors. Dendritic cells (DCs) are professional promoters of immune responses against tumor antigens with the outstanding ability to coordinate the innate and adaptive immune systems. Evidence suggests that there is a decrease in both the number and function of DCs in cancer patients. Therefore, they represent a strong scaffold for therapeutic interventions. DC vaccination (DCV) is safe, and the antitumoral responses induced are well established in solid tumors. Although the addition of checkpoint inhibitors (CPIs) to chemotherapy has provided new options in the treatment of cancer, they have shown no clinical benefit in immune desert tumors or in those tumors with dysfunctional or exhausted T-cells. In this way, DC-based therapy has demonstrated the ability to modify the tumor microenvironment for immune enriched tumors and to potentiate systemic host immune responses as an active approach to treating cancer patients. Application of DCV in cancer seeks to obtain long-term antitumor responses through an improved T-cell priming by enhancing previous or generating de novo immune responses. To date, DCV has induced immune responses in the peripheral blood of patients without a significant clinical impact on outcome. Thus, improvements in vaccines formulations, selection of patients based on biomarkers and combinations with other antitumoral therapies are needed to enhance patient survival. In this work, we review the role of DCV in different solid tumors with their strengths and weaknesses, and we finally mention new trends to improve the efficacy of this immune strategy.
Language	English
Publishing date	2024-02-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers16050981
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Article: Modification of Breast Cancer Milieu with Chemotherapy plus Dendritic Cell Vaccine: An Approach to Select Best Therapeutic Strategies.

Mejías Sosa, Luis / López-Janeiro, Álvaro / Córdoba Iturriagagoitia, Alicia / Sala, Pablo / Solans, Belén P / Hato, Laura / Inogés, Susana / López-Díaz de Cerio, Ascensión / Guillén-Grima, Francisco / Espinós, Jaime / De La Cruz, Susana / Lozano, María Dolores / Idoate, Miguel A / Santisteban, Marta

Biomedicines

2023 Volume 11, Issue 2

Abstract: Background: The addition of dendritic cell vaccines (DCV) to NAC could induce immune responses in those patients with residual disease (RD) by transforming the tumor microenvironment.: Methods: Core diagnostic biopsies and surgical specimens from 80 ... ...

Abstract	Background: The addition of dendritic cell vaccines (DCV) to NAC could induce immune responses in those patients with residual disease (RD) by transforming the tumor microenvironment. Methods: Core diagnostic biopsies and surgical specimens from 80 patients (38 in the vaccinated group plus NAC (VG) and 42 in the control group (CG, treated only with NAC) were selected. We quantify TILs (CD8, CD4 and CD45RO) using immunohistochemistry and the automated cellular imaging system (ACIS III) in paired samples. Results: A CD8 rise in TNBC samples was observed after NAC plus DCV, changing from 4.48% in the biopsy to 6.70% in the surgical specimen, not reaching statistically significant differences ( Conclusion: Our findings suggest that patients with TNBC could benefit from the stimulation of the antitumor immune system by using DCV together with NAC.
Language	English
Publishing date	2023-01-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11020238
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Article ; Online: C5a elevation in convalescents from severe COVID-19 is not associated with early complement activation markers C3bBbP or C4d.

Kowalska, Daria / Kuźniewska, Alicja / Senent, Yaiza / Tavira, Beatriz / Inogés, Susana / López-Díaz de Cerio, Ascensión / Pio, Ruben / Okrój, Marcin / Yuste, José Ramón

Frontiers in immunology

2022 Volume 13, Page(s) 946522

Abstract: Numerous publications have underlined the link between complement C5a and the clinical course of COVID-19. We previously reported that levels of C5a remain high in the group of severely ill patients up to 90 days after hospital discharge. We have now ... ...

Abstract	Numerous publications have underlined the link between complement C5a and the clinical course of COVID-19. We previously reported that levels of C5a remain high in the group of severely ill patients up to 90 days after hospital discharge. We have now evaluated which complement pathway fuels the elevated levels of C5a during hospitalization and follow-up. The alternative pathway (AP) activation marker C3bBbP and the soluble fraction of C4d, a footprint of the classical/lectin (CP/LP) pathway, were assessed by immunoenzymatic assay in a total of 188 serial samples from 49 patients infected with SARS-CoV-2. Unlike C5a, neither C3bBbP nor C4d readouts rose proportionally to the severity of the disease. Detailed correlation analyses in hospitalization and follow-up samples collected from patients of different disease severity showed significant positive correlations of AP and CP/LP markers with C5a in certain groups, except for the follow-up samples of the patients who suffered from highly severe COVID-19 and presented the highest C5a readouts. In conclusion, there is not a clear link between persistently high levels of C5a after hospital discharge and markers of upstream complement activation, suggesting the existence of a non-canonical source of C5a in patients with a severe course of COVID-19.
MeSH term(s)	Biomarkers/blood ; COVID-19/blood ; COVID-19/immunology ; Complement Activation/immunology ; Complement C3b/immunology ; Complement C4b/immunology ; Complement C5a/analysis ; Complement C5a/immunology ; Complement Factor B/immunology ; Complement System Proteins/immunology ; Humans ; Peptide Fragments/immunology ; SARS-CoV-2
Chemical Substances	Biomarkers ; Peptide Fragments ; Complement C3b (80295-43-8) ; Complement C4b (80295-50-7) ; complement C4d (80295-52-9) ; Complement C5a (80295-54-1) ; Complement System Proteins (9007-36-7) ; Complement Factor B (EC 3.4.21.47)
Language	English
Publishing date	2022-08-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.946522
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Article ; Online: Preclinical development of a humanized chimeric antigen receptor against B cell maturation antigen for multiple myeloma.

Perez-Amill, Lorena / Suñe, Guillermo / Antoñana-Vildosola, Asier / Castella, Maria / Najjar, Amer / Bonet, Jaume / Fernández-Fuentes, Narcis / Inogés, Susana / López, Ascensión / Bueno, Clara / Juan, Manel / Urbano-Ispizua, Álvaro / Martín-Antonio, Beatriz

Haematologica

2021 Volume 106, Issue 1, Page(s) 173–184

Abstract: Multiple myeloma is a prevalent and incurable disease, despite the development of new and effective drugs. The recent development of chimeric antigen receptor (CAR)-T cell therapy has shown impressive results in the treatment of patients with relapsed or ...

Abstract	Multiple myeloma is a prevalent and incurable disease, despite the development of new and effective drugs. The recent development of chimeric antigen receptor (CAR)-T cell therapy has shown impressive results in the treatment of patients with relapsed or refractory hematological B cell malignancies. In the recent years, B-cell maturation antigen (BCMA) has appeared as a promising antigen to target using a variety of immuno-therapy treatments including CART cells, for MM patients. To this end, we generated clinical-grade murine CART cells directed against BCMA, named ARI2m cells. Having demonstrated its efficacy, and in an attempt to avoid the immune rejection of CART cells by the patient, the single chain variable fragment was humanized, creating ARI2h cells. ARI2h cells demonstrated comparable in vitro and in vivo efficacy to ARI2m cells, and superiority in cases of high tumor burden disease. In terms of inflammatory response, ARI2h cells showed a lower TNFα production and lower in vivo toxicity profile. Large-scale expansion of both ARI2m and ARI2h cells was efficiently conducted following Good Manufacturing Practice guidelines, obtaining the target CART cell dose required for treatment of multiple myeloma patients. Moreover, we demonstrate that soluble BCMA and BCMA released in vesicles impacts on CAR-BCMA activity. In summary, this study sets the bases for the implementation of a clinical trial (EudraCT code: 2019-001472-11) to study the efficacy of ARI2h cell treatment for multiple myeloma patients.
MeSH term(s)	Animals ; B-Cell Maturation Antigen ; Humans ; Immunotherapy, Adoptive ; Mice ; Multiple Myeloma/therapy ; Receptors, Chimeric Antigen/genetics ; T-Lymphocytes
Chemical Substances	B-Cell Maturation Antigen ; Receptors, Chimeric Antigen
Language	English
Publishing date	2021-01-01
Publishing country	Italy
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2019.228577
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Article ; Online: Adoptive T-cell therapy with CD45RA-depleted donor in the treatment of cytomegalovirus disease in immunocompromised non-transplant patients.

Yuste, Jose R / López-Díaz de Cerio, Ascensión / Rifón, Jose / Moreno, Cristina / Panizo, María / Inogés, Susana

Antiviral therapy

2019 Volume 24, Issue 4, Page(s) 313–319

Abstract: Cytomegalovirus (CMV) infections can induce severe complications in immunosuppressed patients. Currently, ganciclovir represents the preferred treatment option; however, in patients with resistance or toxicity related to ganciclovir, the therapeutic ... ...

Abstract	Cytomegalovirus (CMV) infections can induce severe complications in immunosuppressed patients. Currently, ganciclovir represents the preferred treatment option; however, in patients with resistance or toxicity related to ganciclovir, the therapeutic options are limited.Cellular immunity plays an important role in the control of viral infections. Adoptive T-cell therapy can contribute to recovering immunological function in immunosuppressed patients. Selective T-cell depletion targeting CD45RA enhances early T-cell recovery and can represent a salvage therapy. In this study, an immunocompromised non-transplanted patient with CMV disease and toxicity to conventional therapy was successfully treated by adoptive transfer of CD45RA-depleted T-cells.
MeSH term(s)	Aged ; Cytomegalovirus Infections/etiology ; Cytomegalovirus Infections/therapy ; Cytomegalovirus Infections/virology ; DNA, Viral ; Donor Selection ; Flow Cytometry ; Humans ; Immunocompromised Host ; Immunoglobulin G/immunology ; Immunotherapy, Adoptive/methods ; Leukocyte Common Antigens/metabolism ; Male ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Tissue Donors ; Treatment Outcome ; Viral Load
Chemical Substances	DNA, Viral ; Immunoglobulin G ; Leukocyte Common Antigens (EC 3.1.3.48)
Language	English
Publishing date	2019-03-26
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	1339842-8
ISSN	2040-2058 ; 1359-6535
ISSN (online)	2040-2058
ISSN	1359-6535
DOI	10.3851/IMP3307
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Article ; Online: Persistence of High Levels of Serum Complement C5a in Severe COVID-19 Cases After Hospital Discharge.

Senent, Yaiza / Inogés, Susana / López-Díaz de Cerio, Ascensión / Blanco, Andres / Campo, Arantxa / Carmona-Torre, Francisco / Sunsundegui, Patricia / González-Martín, Antonio / Ajona, Daniel / Okrój, Marcin / Prósper, Felipe / Pio, Ruben / Yuste, José Ramón / Tavira, Beatriz

Frontiers in immunology

2021 Volume 12, Page(s) 767376

Abstract: Evidence supports a role of complement anaphylatoxin C5a in the pathophysiology of COVID-19. However, information about the evolution and impact of C5a levels after hospital discharge is lacking. We analyzed the association between circulating C5a levels ...

Abstract	Evidence supports a role of complement anaphylatoxin C5a in the pathophysiology of COVID-19. However, information about the evolution and impact of C5a levels after hospital discharge is lacking. We analyzed the association between circulating C5a levels and the clinical evolution of hospitalized patients infected with SARS-CoV-2. Serum C5a levels were determined in 32 hospitalized and 17 non-hospitalized patients from Clinica Universidad de Navarra. One hundred and eighty eight serial samples were collected during the hospitalization stay and up to three months during the follow-up. Median C5a levels were 27.71 ng/ml (25th to 75th percentile: 19.35-34.96) for samples collected during hospitalization,
MeSH term(s)	Aged ; COVID-19/blood ; COVID-19/complications ; COVID-19/immunology ; Complement C5a/metabolism ; Female ; Follow-Up Studies ; Hospitalization ; Humans ; Immunity, Innate ; Male ; Middle Aged ; Patient Discharge/statistics & numerical data ; Respiration Disorders/blood ; Respiration Disorders/etiology ; Respiration Disorders/immunology ; Risk Factors ; SARS-CoV-2 ; Severity of Illness Index
Chemical Substances	Complement C5a (80295-54-1)
Language	English
Publishing date	2021-11-18
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.767376
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Article: Final results regarding the addition of dendritic cell vaccines to neoadjuvant chemotherapy in early HER2-negative breast cancer patients: clinical and translational analysis.

Santisteban, Marta / Solans, Belén Pérez / Hato, Laura / Urrizola, Amaia / Mejías, Luis Daniel / Salgado, Esteban / Sánchez-Bayona, Rodrigo / Toledo, Estefanía / Rodríguez-Spiteri, Natalia / Olartecoechea, Begoña / Idoate, Miguel Angel / López-Díaz de Cerio, Ascensión / Inogés, Susana

Therapeutic advances in medical oncology

2021 Volume 13, Page(s) 17588359211064653

Abstract: Background: Primary breast cancer (BC) has shown a higher immune infiltration than the metastatic disease, justifying the optimal scenario for immunotherapy. Recently, neoadjuvant chemotherapy (NAC) combined with immune checkpoint inhibitors has ... ...

Abstract	Background: Primary breast cancer (BC) has shown a higher immune infiltration than the metastatic disease, justifying the optimal scenario for immunotherapy. Recently, neoadjuvant chemotherapy (NAC) combined with immune checkpoint inhibitors has demonstrated a gain in pathological complete responses (tpCR) in patients with BC. The aim of our study is to evaluate the safety, feasibility, and efficacy of the addition of dendritic cell vaccines (DCV) to NAC in HER2-negative BC patients. Methods: Thirty-nine patients with early BC received DCV together with NAC conforming the vaccinated group (VG) and compared with 44 patients as the control group (CG). All patients received anthracyclines and taxanes-based NAC (ddECx4→Dx4) followed by surgery ± radiotherapy ± hormonotherapy. Results: The tpCR rate was 28.9% in the VG and 9.09% in the CG ( Conclusion: The combination of DCV plus NAC is safe and increases tpCR, with a significant benefit among PD-L1-negative tumors. DCV modify tumor milieu and perform cellular and humoral responses in peripheral blood with no impact in outcome. Trial registration: ClinicalTrials.gov number: NCT01431196. EudraCT 2009-017402-36.
Language	English
Publishing date	2021-12-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2503443-1
ISSN	1758-8359 ; 1758-8340
ISSN (online)	1758-8359
ISSN	1758-8340
DOI	10.1177/17588359211064653
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Article ; Online: Preclinical evaluation of a synthetic peptide vaccine against SARS-CoV-2 inducing multiepitopic and cross-reactive humoral neutralizing and cellular CD4 and CD8 responses.

Aparicio, Belén / Casares, Noelia / Egea, Josune / Ruiz, Marta / Llopiz, Diana / Maestro, Sheila / Olagüe, Cristina / González-Aseguinolaza, Gloria / Smerdou, Cristian / López-Díaz de Cerio, Ascensión / Inogés, Susana / Prósper, Felipe / Yuste, José R / Carmona-Torre, Francisco / Reina, Gabriel / Lasarte, Juan J / Sarobe, Pablo

Emerging microbes & infections

2021 Volume 10, Issue 1, Page(s) 1931–1946

Abstract: Identification of relevant epitopes is crucial for the development of subunit peptide vaccines inducing neutralizing and cellular immunity against SARS-CoV-2. Our aim was the characterization of epitopes in the receptor-binding domain (RBD) of SARS-CoV-2 ...

Abstract	Identification of relevant epitopes is crucial for the development of subunit peptide vaccines inducing neutralizing and cellular immunity against SARS-CoV-2. Our aim was the characterization of epitopes in the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein to generate a peptide vaccine. Epitope mapping using a panel of 10 amino acid overlapped 15-mer peptides covering region 401-515 from RBD did not identify linear epitopes when tested with sera from infected individuals or from RBD-immunized mice. However, immunization of mice with these 15-mer peptides identified four peptides located at region 446-480 that induced antibodies recognizing the peptides and RBD/S1 proteins. Immunization with peptide 446-480 from S protein formulated with Freund's adjuvant or with CpG oligodeoxinucleotide/Alum induced polyepitopic antibody responses in BALB/c and C56BL/6J mice, recognizing RBD (titres of 3 × 10
MeSH term(s)	Adjuvants, Immunologic/administration & dosage ; Animals ; Antibodies, Neutralizing/blood ; Antibodies, Neutralizing/immunology ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19 Vaccines/immunology ; COVID-19 Vaccines/standards ; Cross Reactions/immunology ; Epitope Mapping ; Epitopes, B-Lymphocyte ; Epitopes, T-Lymphocyte/immunology ; Humans ; Immunity, Cellular ; Immunity, Humoral ; Immunization ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Transgenic ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/immunology ; Vaccines, Subunit/immunology ; Vaccines, Synthetic/immunology
Chemical Substances	Adjuvants, Immunologic ; Antibodies, Neutralizing ; COVID-19 Vaccines ; Epitopes, B-Lymphocyte ; Epitopes, T-Lymphocyte ; Spike Glycoprotein, Coronavirus ; Vaccines, Subunit ; Vaccines, Synthetic
Language	English
Publishing date	2021-08-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2681359-2
ISSN	2222-1751 ; 2222-1751
ISSN (online)	2222-1751
ISSN	2222-1751
DOI	10.1080/22221751.2021.1978823
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Article ; Online: Antibody-dependent cell cytotoxicity: immunotherapy strategies enhancing effector NK cells.

Ochoa, Maria Carmen / Minute, Luna / Rodriguez, Inmaculada / Garasa, Saray / Perez-Ruiz, Elisabeth / Inogés, Susana / Melero, Ignacio / Berraondo, Pedro

Immunology and cell biology

2017 Volume 95, Issue 4, Page(s) 347–355

Abstract: Antibody-dependent cellular cytotoxicity (ADCC) is a set of mechanisms that target cells coated with IgG antibodies of the proper subclasses (IgG1 in the human) to be the prey of cell-to-cell cytolysis executed by immune cells expressing FcRIIIA (CD16A). ...

Abstract	Antibody-dependent cellular cytotoxicity (ADCC) is a set of mechanisms that target cells coated with IgG antibodies of the proper subclasses (IgG1 in the human) to be the prey of cell-to-cell cytolysis executed by immune cells expressing FcRIIIA (CD16A). These effectors include not only natural killer (NK) cells but also other CD16
MeSH term(s)	Animals ; Antibody Affinity ; Antibody-Dependent Cell Cytotoxicity ; Antigens, Neoplasm/immunology ; Cytokines/metabolism ; Humans ; Immunotherapy, Adoptive/methods ; Killer Cells, Natural/immunology ; Killer Cells, Natural/transplantation ; Macrophages/physiology ; Molecular Targeted Therapy ; Neoplasms/immunology ; Neoplasms/therapy ; Receptors, Antigen, T-Cell, gamma-delta/metabolism ; Receptors, IgG/metabolism ; T-Lymphocytes/immunology ; Toll-Like Receptors/metabolism
Chemical Substances	Antigens, Neoplasm ; Cytokines ; FCGR3A protein, human ; Receptors, Antigen, T-Cell, gamma-delta ; Receptors, IgG ; Toll-Like Receptors
Language	English
Publishing date	2017-02-21
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	284057-1
ISSN	1440-1711 ; 0818-9641
ISSN (online)	1440-1711
ISSN	0818-9641
DOI	10.1038/icb.2017.6
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Article ; Online: Assessing the impact of the addition of dendritic cell vaccination to neoadjuvant chemotherapy in breast cancer patients: A model-based characterization approach.

Solans, Belén P / López-Díaz de Cerio, Ascensión / Elizalde, Arlette / Pina, Luis Javier / Inogés, Susana / Espinós, Jaime / Salgado, Esteban / Mejías, Luis Daniel / Trocóniz, Iñaki F / Santisteban, Marta

British journal of clinical pharmacology

2019 Volume 85, Issue 8, Page(s) 1670–1683

MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast/immunology ; Breast/pathology ; Breast Neoplasms/immunology ; Breast Neoplasms/mortality ; Breast Neoplasms/pathology ; Breast Neoplasms/therapy ; Cancer Vaccines/administration & dosage ; Cancer Vaccines/immunology ; Case-Control Studies ; Chemotherapy, Adjuvant ; Cohort Studies ; Computer Simulation ; Dendritic Cells/immunology ; Female ; Humans ; Mastectomy ; Middle Aged ; Models, Biological ; Neoadjuvant Therapy/methods ; Progression-Free Survival ; Tumor Burden/immunology
Chemical Substances	Cancer Vaccines
Language	English
Publishing date	2019-06-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Validation Study
ZDB-ID	188974-6
ISSN	1365-2125 ; 0306-5251 ; 0264-3774
ISSN (online)	1365-2125
ISSN	0306-5251 ; 0264-3774
DOI	10.1111/bcp.13947
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