5 results on '"Navarro-Zapata A"'
Search Results
2. Immunotherapy: MEMORY-LIKE NK CELLS: A PROMISING THERAPY FOR EWING SARCOMA
- Author
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C. Martín Cortázar, A. Navarro Zapata, C. Mestre Durán, L. Clares Villa, K. Al-Akioui, C. Ferreras, and A. Perez-Martinez
- Subjects
Cancer Research ,Transplantation ,Oncology ,Immunology ,Immunology and Allergy ,Cell Biology ,Genetics (clinical) - Published
- 2022
3. A Mathematical Description of the Bone Marrow Dynamics during CAR T-Cell Therapy in B-Cell Childhood Acute Lymphoblastic Leukemia
- Author
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Cristina Blázquez Goñi, Cristina Ferreras, Álvaro Martínez-Rubio, Salvador Chulián, Manuel Ramírez Orellana, Alfonso Navarro-Zapata, María Rosa, Víctor M. Pérez-García, Antonio Pérez Martínez, Matemáticas, [Martínez-Rubio,Á, Chulián,S, Rosa,M] Department of Mathematics, Universidad de Cádiz, Puerto Real, Cádiz, Spain. [Martínez-Rubio,Á, Blázquez Goñi,C, Rosa,M] Biomedical Research and Innovation Institute of Cádiz (INiBICA), Hospital Universitario Puerta del Mar, Cádiz, Spain. [Blázquez Goñi,C] Department of Pediatric Hematology and Oncology, Hospital de Jerez, Cádiz, Spain. [Ramírez Orellana,M] Department of Paediatric Haematology and Oncology, Instituto Investigación Sanitaria La Princesa, Hospital Infantil Universitario Niño Jesús, Madrid, Spain. [Pérez Martínez,A, Navarro-Zapata,A, Ferreras,C] Translational Research in Pediatric Oncology, Hematopoietic Transplantation and Cell Therapy, IdiPAZ, Hospital Universitario La Paz, Madrid, Spain. [Pérez Martínez,A] Pediatric Hemato-Oncology Department, Hospital Universitario La Paz, Madrid, Spain. [Pérez-García,VM] Mathematical Oncology Laboratory (MOLAB), Instituto de Matemática Aplicada a la Ciencia y la Ingeniería, Universidad de Castilla-La Mancha, Ciudad Real, Spain. [Pérez-García,VM] Departamento de Matemáticas, Escuela Técnica Superior de Ingenieros Industriales, Universidad de Castilla-La Mancha, Ciudad Real, Spain., and This work was partially supported by the Fundación Española para la Ciencia y la Tecnología (UCA PR214), the Asociación Pablo Ugarte (APU, Spain), Junta de Comunidades de Castilla-La Mancha (SBPLY/17/180501/000154), Ministry of Science and Technology, Spain (PID2019-110895RB-I00), and Inversión Territorial Integrada de la Provincia de Cádiz (ITI-0038-2019).
- Subjects
0301 basic medicine ,CAR T ,Leucemia-linfoma linfoblástico de células precursoras ,Disease ,Immunotherapy, Adoptive ,Anatomy::Hemic and Immune Systems::Immune System::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::Lymphocyte Subsets::B-Lymphocyte Subsets [Medical Subject Headings] ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical [Medical Subject Headings] ,0302 clinical medicine ,Subgrupos de linfocitos B ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, Biological [Medical Subject Headings] ,Biology (General) ,Young adult ,Child ,Spectroscopy ,B-Lymphocytes ,B cell ,Dynamics (mechanics) ,Médula ósea ,Diseases::Hemic and Lymphatic Diseases::Lymphatic Diseases::Lymphoproliferative Disorders::Leukemia, Lymphoid::Precursor Cell Lymphoblastic Leukemia-Lymphoma::Precursor B-Cell Lymphoblastic Leukemia-Lymphoma [Medical Subject Headings] ,General Medicine ,Computer Science Applications ,Chemistry ,Leukemia ,Treatment Outcome ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Niño ,Modelos teóricos ,Car t cells ,bone marrow ,QH301-705.5 ,acute lymphoblastic leukemia ,Models, Biological ,Catalysis ,Receptores quiméricos de antígenos ,Article ,Inorganic Chemistry ,03 medical and health sciences ,Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ,medicine ,Humans ,Persons::Persons::Age Groups::Child [Medical Subject Headings] ,Physical and Theoretical Chemistry ,QD1-999 ,Molecular Biology ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings] ,business.industry ,Organic Chemistry ,Anatomy::Hemic and Immune Systems::Immune System::Bone Marrow [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunization::Immunization, Passive::Adoptive Transfer::Immunotherapy, Adoptive [Medical Subject Headings] ,medicine.disease ,Chimeric antigen receptor ,030104 developmental biology ,Phenomena and Processes::Immune System Phenomena::Immunity::Adaptive Immunity::Immunologic Memory [Medical Subject Headings] ,Cancer research ,Bone marrow ,business ,Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::B-Lymphocytes [Medical Subject Headings] ,Immunologic Memory ,mathematical model - Abstract
Chimeric Antigen Receptor (CAR) T-cell therapy has demonstrated high rates of response in recurrent B-cell Acute Lymphoblastic Leukemia in children and young adults. Despite this success, a fraction of patients' experience relapse after treatment. Relapse is often preceded by recovery of healthy B cells, which suggests loss or dysfunction of CAR T-cells in bone marrow. This site is harder to access, and thus is not monitored as frequently as peripheral blood. Understanding the interplay between B cells, leukemic cells, and CAR T-cells in bone marrow is paramount in ascertaining the causes of lack of response. In this paper, we put forward a mathematical model representing the interaction between constantly renewing B cells, CAR T-cells, and leukemic cells in the bone marrow. Our model accounts for the maturation dynamics of B cells and incorporates effector and memory CAR T-cells. The model provides a plausible description of the dynamics of the various cellular compartments in bone marrow after CAR T infusion. After exploration of the parameter space, we found that the dynamics of CAR T product and disease were independent of the dose injected, initial B-cell load, and leukemia burden. We also show theoretically the importance of CAR T product attributes in determining therapy outcome, and have studied a variety of possible response scenarios, including second dosage schemes. We conclude by setting out ideas for the refinement of the model., This work was partially supported by the Fundacion Espanola para la Ciencia y la Tecnologia (UCA PR214), the Asociacion Pablo Ugarte (APU, Spain), Junta de Comunidades de Castilla-La Mancha (SBPLY/17/180501/000154), Ministry of Science and Technology, Spain (PID2019110895RB-I00), and Inversion Territorial Integrada de la Provincia de Cadiz (ITI-0038-2019).
- Published
- 2021
4. A Mathematical Description of the Bone Marrow Dynamics of CAR T-Cell Therapy in B-cell Childhood Acute Lymphoblastic Leukemia
- Author
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Cristina Blázquez Goñi, Salvador Chulián, Alfonso Navarro-Zapata, Víctor M. Pérez-García, Antonio Pérez Martínez, Manuel Ramírez Orellana, Cristina Ferreras, María Rosa, and Álvaro Martínez-Rubio
- Subjects
applied_mathematics ,medicine.anatomical_structure ,B-Cell Childhood Acute Lymphoblastic Leukemia ,business.industry ,medicine ,Cancer research ,CAR T-cell therapy ,Bone marrow ,Car t cells ,business ,B cell - Abstract
Chimeric Antigen Receptor (CAR) T-cell therapy has demonstrated high rates of response in recurrent B-cell Acute Lymphoblastic Leukemia in children and young adults. Despite this success, a fraction of patients experience relapse after treatment. Relapse is often preceded by recovery of healthy B cells, which suggests loss or dysfunction of CAR T cells in bone marrow. This site is harder to access, and thus is not monitored as frequently as peripheral blood. Understanding the interplay between B cells, leukemic cells and CAR T cells in bone marrow is paramount in ascertaining the causes of lack of response. In this paper, we put forward a mathematical model representing the interaction between constantly renewing B cells, CAR T cells and leukemic cells in the bone marrow. Our model accounts for the maturation dynamics of B cells and incorporates effector and memory CAR T cells. The model provides a plausible description of the dynamics of the various cellular compartments in bone marrow after CAR T infusion. After exploration of the parameter space, we found that the dynamics of CAR T product and disease were independent of the dose injected, initial B-cell load and tumor burden. We also show theoretically the importance of CAR T product attributes in determining therapy outcome, and have studied a variety of possible response scenarios, including second dosage schemes. We conclude by setting out ideas for the refinement of the model.
- Published
- 2021
5. Optimizing the procedure to manufacture clinical‐grade NK cells for adoptive immunotherapy
- Author
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Lucía Fernández, Alfonso Navarro-Zapata, Cristina Ferreras, Diego Lanzarot, Alicia Pernas, Carlos Rodriguez-Antolin, Alejandra Leivas, Marta Cobo, Aurora Viejo, Joaquín Martínez, Gema Casado, Beatriz Ruz-Caracuel, Carmen Mestre, María Vela, Adela Escudero, Isabel Mirones, Nerea Matamala, Adrián Fernández, Antonio Pérez-Martínez, and UAM. Departamento de Pediatría
- Subjects
0301 basic medicine ,Cancer Research ,Medicina ,medicine.medical_treatment ,T cell ,Cell ,NK cell activation and expansion ,Peripheral blood mononuclear cell ,lcsh:RC254-282 ,Article ,Oncología ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Cancer immunotherapy ,Clinical‐grade manufacturing ,medicine ,Hematología ,clinical-grade manufacturing ,Cytotoxicity ,Chemistry ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,CliniMACS Prodigy ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Cell culture ,030220 oncology & carcinogenesis ,Cancer research ,Stem cell ,NKAE cells ,NK cell immunotherapy - Abstract
Natural killer (NK) cells represent promising tools for cancer immunotherapy. We report the optimization of an NK cell activation–expansion process and its validation on clinical‐scale. Methods: RPMI‐1640, stem cell growth medium (SCGM), NK MACS and TexMACS were used as culture mediums. Activated and expanded NK cells (NKAE) were obtained by coculturing total peripheral blood mononuclear cells (PBMC) or CD45RA+ cells with irradiated K562mbIL15‐41BBL or K562mbIL21‐41BBL. Fold increase, NK cell purity, activation status, cytotoxicity and transcriptome profile were analyzed. Clinical‐grade NKAE cells were manufactured in CliniMACS Prodigy. Results: NK MACS and TexMACs achieved the highest NK cell purity and lowest T cell contamination. Obtaining NKAE cells from CD45RA+ cells was feasible although PBMC yielded higher total cell numbers and NK cell purity than CD45RA+ cells. The highest fold expansion and NK purity were achieved by using PBMC and K562mbIL21‐41BBL cells. However, no differences in activation and cytotoxicity were found when using either NK cell source or activating cell line. Transcriptome profile showed to be different between basal NK cells and NKAE cells expanded with K562mbIL21‐41BBL or K562mbIL15‐41BBL. Clinical‐grade manufactured NKAE cells complied with the specifications from the Spanish Regulatory Agency. Conclusions: GMP‐grade NK cells for clinical use can be obtained by using different starting cells and aAPC, This work was supported by the National Health Service of Spain, Instituto de Salud Carlos III (ISCIII), FONDOS FEDER grant (FIS) PI18/01301 to Pérez‐Martínez A, CRIS Foundation to Beat Cancer to Escudero A, Fernández A; Navarro A, Mirones I, and Fundación Mari Paz Jiménez Casado and La Sonrisa de Álex to Vela M.
- Published
- 2021
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