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Dive into the research topics where Caridad Martinez is active.

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Featured researches published by Caridad Martinez.


Blood | 2014

Long-term outcome after haploidentical stem cell transplant and infusion of T cells expressing the inducible caspase 9 safety transgene

Xiaoou Zhou; Antonio Di Stasi; Siok-Keen Tey; Robert A. Krance; Caridad Martinez; Kathryn Leung; April G. Durett; Meng Fen Wu; Hao Liu; Ann M. Leen; Barbara Savoldo; Yu Feng Lin; Bambi Grilley; Adrian P. Gee; David M. Spencer; Cliona M. Rooney; Helen E. Heslop; Malcolm K. Brenner; Gianpietro Dotti

Adoptive transfer of donor-derived T lymphocytes expressing a safety switch may promote immune reconstitution in patients undergoing haploidentical hematopoietic stem cell transplant (haplo-HSCT) without the risk for uncontrolled graft versus host disease (GvHD). Thus, patients who develop GvHD after infusion of allodepleted donor-derived T cells expressing an inducible human caspase 9 (iC9) had their disease effectively controlled by a single administration of a small-molecule drug (AP1903) that dimerizes and activates the iC9 transgene. We now report the long-term follow-up of 10 patients infused with such safety switch-modified T cells. We find long-term persistence of iC9-modified (iC9-T) T cells in vivo in the absence of emerging oligoclonality and a robust immunologic benefit, mediated initially by the infused cells themselves and subsequently by an apparently accelerated reconstitution of endogenous naive T lymphocytes. As a consequence, these patients have immediate and sustained protection from major pathogens, including cytomegalovirus, adenovirus, BK virus, and Epstein-Barr virus in the absence of acute or chronic GvHD, supporting the beneficial effects of this approach to immune reconstitution after haplo-HSCT. This study was registered at www.clinicaltrials.gov as #NCT00710892.


Science Translational Medicine | 2015

CMV-specific T cells generated from naïve T cells recognize atypical epitopes and may be protective in vivo

Patrick J. Hanley; J. Joseph Melenhorst; Sarah Nikiforow; Phillip Scheinberg; James W. Blaney; Gail J. Demmler-Harrison; C. Russell Cruz; Sharon Lam; Robert A. Krance; Kathryn Leung; Caridad Martinez; Hao Liu; Helen E. Heslop; Cliona M. Rooney; Elizabeth J. Shpall; A. John Barrett; Catherine M. Bollard

CMV-specific T cells, derived from the naïve population, recognize different epitopes of CMV than do memory-derived T cells and may be functional and protective in vivo. Sourcing CMV immunotherapy Immunotherapy—such as adoptive T cell therapy—is making headway in treating cancer, autoimmunity, and infectious disease. Indeed, adoptive transfer of cytomegalovirus (CMV)–specific T cells can restore immunity to the virus. However, these cells have been primarily derived from memory cells from CMV-seropositive individuals, which limits the donor pool. Now, Hanley et al. demonstrate that CMV-specific T cells can be derived from naïve T cells taken from CMV-seronegative people. These cells react to different epitopes than the memory cell–derived T cells but with similar avidity. What’s more, these cells were associated with periods of CMV-free survival when transplanted into patients. These data support expanded trials of adoptive therapy of CMV-restricted T cells from seronegative donors. Adoptive transfer of cytomegalovirus (CMV)–specific T cells derived from adult seropositive donors can effectively restore antiviral immunity after transplantation. However, CMV-seronegative donors lack CMV-specific memory T cells, which restricts the availability of virus-specific T cells for immunoprophylaxis. We demonstrate the feasibility of deriving CMV-specific T cells from naïve cells for T cell therapy. Naïve T cells primed to recognize CMV were restricted to different, atypical epitopes than T cells derived from CMV-seropositive individuals; however, these two cell populations had similar avidities. CMV-seropositive individuals also had T cells recognizing these atypical epitopes, but these cells had a lower avidity than those derived from the seronegative subjects, which suggests that high-avidity T cells to these epitopes may be lost over time. Indeed, recipients of cord blood (CB) grafts who did not develop CMV were found by clonotypic analysis to have T cells recognizing atypical CMVpp65 epitopes. Therefore, we examined unmanipulated CB units and found that T cells with T cell receptors restricted by atypical epitopes were the most common, which may explain why these T cells expanded. When infused to recipients, naïve donor–derived virus-specific T cells that recognized atypical epitopes were associated with prolonged periods of CMV-free survival and complete remission. These data suggest that naïve-derived T cells from seronegative patients may be an additional source of cells for CMV immunoprophylaxis.


The Journal of Allergy and Clinical Immunology | 2012

Excellent survival after sibling or unrelated donor stem cell transplantation for chronic granulomatous disease.

Caridad Martinez; Sweta S. Shah; William T. Shearer; Howard M. Rosenblatt; Mary E. Paul; Javier Chinen; Kathryn Leung; Alana A. Kennedy-Nasser; Malcolm K. Brenner; Helen E. Heslop; Hao Liu; Meng Fen Wu; Imelda C. Hanson; Robert A. Krance

BACKGROUND Matched related donor (MRD) hematopoietic stem cell transplantation (HSCT) is a successful treatment for chronic granulomatous disease (CGD), but the safety and efficacy of HSCT from unrelated donors is less certain. OBJECTIVE We evaluated the outcomes and overall survival in patients with CGD after HSCT. METHODS We report the outcomes for 11 children undergoing HSCT from an MRD (n = 4) or an HLA-matched unrelated donor (MUD) (n = 7); 9 children were boys, and the median age was 3.8 years (range, 1-13 years). We treated both X-linked (n = 9) and autosomal recessive (n = 2) disease. Nine children had serious clinical infections before transplantation. The conditioning regimens contained busulfan, cyclophosphamide, cytarabine, or fludarabine according to the donor used. All patients received alemtuzumab (anti-CD52 antibody). Additional graft-versus-host disease (GvHD) prophylaxis included cyclosporine and methotrexate for MUD recipients and cyclosporine and prednisone for MRD recipients. RESULTS Neutrophil recovery took a median of 16 days (range, 12-40 days) and 18 days (range, 13-24 days) for MRD and MUD recipients, respectively. Full donor neutrophil engraftment occurred in 9 patients, and 2 had stable mixed chimerism; all patients had sustained correction of neutrophil oxidative burst defect. Four patients had grade I skin acute GVHD responding to topical treatment. No patient had grade II to IV acute GvHD or chronic GvHD. All patients are alive between 1 and 8 years after HSCT. CONCLUSION For CGD, equivalent outcomes can be obtained with MRD or MUD stem cells, and HSCT should be considered an early treatment option.


Clinical and Experimental Immunology | 2014

Vaccine-associated varicella and rubella infections in severe combined immunodeficiency with isolated CD4 lymphocytopenia and mutations in IL7R detected by tandem whole exome sequencing and chromosomal microarray

D. K. Bayer; Caridad Martinez; Hanne Sørmo Sorte; Lisa R. Forbes; G. J. Demmler-Harrison; I. C. Hanson; N. M. Pearson; Lenora M. Noroski; S. R. Zaki; W. J. Bellini; Magalie S. Leduc; Yaping Yang; Christine M. Eng; Ankita Patel; Olaug K. Rødningen; Donna M. Muzny; Richard A. Gibbs; Ian M. Campbell; Chad A. Shaw; M. W. Baker; Victor Wei Zhang; James R. Lupski; Jordan S. Orange; Filiz O. Seeborg; Asbjørg Stray-Pedersen

In areas without newborn screening for severe combined immunodeficiency (SCID), disease‐defining infections may lead to diagnosis, and in some cases, may not be identified prior to the first year of life. We describe a female infant who presented with disseminated vaccine‐acquired varicella (VZV) and vaccine‐acquired rubella infections at 13 months of age. Immunological evaluations demonstrated neutropenia, isolated CD4 lymphocytopenia, the presence of CD8+ T cells, poor lymphocyte proliferation, hypergammaglobulinaemia and poor specific antibody production to VZV infection and routine immunizations. A combination of whole exome sequencing and custom‐designed chromosomal microarray with exon coverage of primary immunodeficiency genes detected compound heterozygous mutations (one single nucleotide variant and one intragenic copy number variant involving one exon) within the IL7R gene. Mosaicism for wild‐type allele (20–30%) was detected in pretransplant blood and buccal DNA and maternal engraftment (5–10%) demonstrated in pretransplant blood DNA. This may be responsible for the patients unusual immunological phenotype compared to classical interleukin (IL)‐7Rα deficiency. Disseminated VZV was controlled with anti‐viral and immune‐based therapy, and umbilical cord blood stem cell transplantation was successful. Retrospectively performed T cell receptor excision circle (TREC) analyses completed on neonatal Guthrie cards identified absent TREC. This case emphasizes the danger of live viral vaccination in severe combined immunodeficiency (SCID) patients and the importance of newborn screening to identify patients prior to high‐risk exposures. It also illustrates the value of aggressive pathogen identification and treatment, the influence newborn screening can have on morbidity and mortality and the significant impact of newer genomic diagnostic tools in identifying the underlying genetic aetiology for SCID patients.


IEEE Transactions on Nuclear Science | 2005

Comparison of radiation hardness of P-in-N, N-in-N, and N-in-P silicon pad detectors

M. Lozano; G. Pellegrini; C. Fleta; C. Loderer; J.M. Rafí; M. Ullan; F. Campabadal; Caridad Martinez; M. Key; G. Casse; Phillip Allport

The very high radiation fluence expected at LHC (Large Hadron Collider) at CERN will induce serious changes in the electrical properties of the silicon detectors that will be used in the internal layers of the experiments (ATLAS, CMS, LHCb). To understand the influence of the fabrication technology in the radiation-induced degradation, silicon detectors were fabricated simultaneously with the three different possible technologies, P-in-N, N-in-N, and N-in-P, on standard and oxygenated float-zone silicon wafers. The diodes were irradiated with protons to fluences up to 10/sup 15/ cm/sup -2/. The measurements of the electrical characteristics, current-voltage and capacitance-voltage, are presented for the detectors manufactured with the three technologies. In terms of alpha factor (leakage current) the three technologies behave similarly. In terms of beta factor (effective doping concentration) N-in-P devices show the best performances.


Blood | 2017

Immune reconstitution and survival of 100 SCID patients post-hematopoietic cell transplant: A PIDTC natural history study

Jennifer Heimall; Brent R. Logan; Morton J. Cowan; Luigi D. Notarangelo; Linda M. Griffith; Jennifer M. Puck; Donald B. Kohn; Michael A. Pulsipher; Suhag Parikh; Caridad Martinez; Neena Kapoor; Richard J. O'Reilly; Michael Boyer; Sung-Yun Pai; Frederick Goldman; Lauri Burroughs; Sharat Chandra; Morris Kletzel; Monica S. Thakar; James A. Connelly; Geoff D.E. Cuvelier; Blachy J. Dávila Saldaña; Alan P. Knutsen; Kathleen E. Sullivan; Kenneth B. DeSantes; Alfred P. Gillio; Elie Haddad; Aleksandra Petrovic; Troy C. Quigg; Angela Smith

The Primary Immune Deficiency Treatment Consortium (PIDTC) is enrolling children with severe combined immunodeficiency (SCID) to a prospective natural history study. We analyzed patients treated with allogeneic hematopoietic cell transplantation (HCT) from 2010 to 2014, including 68 patients with typical SCID and 32 with leaky SCID, Omenn syndrome, or reticular dysgenesis. Most (59%) patients were diagnosed by newborn screening or family history. The 2-year overall survival was 90%, but was 95% for those who were infection-free at HCT vs 81% for those with active infection (P = .009). Other factors, including the diagnosis of typical vs leaky SCID/Omenn syndrome, diagnosis via family history or newborn screening, use of preparative chemotherapy, or the type of donor used, did not impact survival. Although 1-year post-HCT median CD4 counts and freedom from IV immunoglobulin were improved after the use of preparative chemotherapy, other immunologic reconstitution parameters were not affected, and the potential for late sequelae in extremely young infants requires additional evaluation. After a T-cell-replete graft, landmark analysis at day +100 post-HCT revealed that CD3 < 300 cells/μL, CD8 < 50 cells/μL, CD45RA < 10%, or a restricted Vβ T-cell receptor repertoire (<13 of 24 families) were associated with the need for a second HCT or death. In the modern era, active infection continues to pose the greatest threat to survival for SCID patients. Although newborn screening has been effective in diagnosing SCID patients early in life, there is an urgent need to identify validated approaches through prospective trials to ensure that patients proceed to HCT infection free. The trial was registered at www.clinicaltrials.gov as #NCT01186913.


european conference on radiation and its effects on components and systems | 2001

Novel results on fluence dependence and annealing behaviour of oxygenated and non-oxygenated silicon detectors

Caridad Martinez; J.M. Rafí; M. Lozano; F. Campabadal; J. Santander; L. Fonseca; M. Ullan; A. Moreno

This work presents the latest results on electrical properties degradation of silicon radiation detectors manufactured at the Institut de Microelectronica de Barcelona (IMB-CNM) subjected to proton irradiation at CERN, Switzerland, for high-energy physics (HEP) applications. The evolution of full depletion voltage and leakage current with fluence as well as their annealing behavior with time were studied. The results obtained extend the previous understanding of the role played by technology and oxygenated material in hardening silicon radiation detectors.


Nuclear Instruments & Methods in Physics Research Section A-accelerators Spectrometers Detectors and Associated Equipment | 1989

Transverse profile of electron showers in a lead-glass calorimeter

F. Bianchi; E. Castelli; P. Checchia; R. Cirio; Mp Clara; A. De Angelis; A. Ferrer; G. Galeazzi; D. Gamba; U. Gasparini; M Innocente; L. Lanceri; I Lippi; A. Lopez; J. Marco; Caridad Martinez; Mirco Mazzucato; E Menichetti; M Pegoraro; C. Pinori; P. Poropat; R. Ragazzon; G Rinaudo; Alessandra Romero; P. Ronchese; A. Ruiz; F. Scuri; A. Sebastia; M. Sessa; F. Simonetto

Abstract As a part of a large experimental program aiming to produce high quality calibration data for the Forward ElectroMagnetic Calorimeter (FEMC) of the DELPHI detector at LEP, special runs were devoted to the study of the transverse profile of electromagnetic showers in lead glass. Results of this study are presented.


Pediatric Blood & Cancer | 2011

Children with acute leukemia: a comparison of outcomes from allogeneic blood stem cell and bone marrow transplantation.

Yu-Feng Lin; David R. Lairson; Wenyaw Chan; Xianglin L. Du; Kathryn Leung; Alana A. Kennedy-Nasser; Caridad Martinez; Helen E. Heslop; Malcolm K. Brenner; Robert A. Krance

The relative merits of peripheral blood stem‐cell transplantation (PBSCT) versus bone marrow transplantation (BMT) for children with standard and high‐risk hematologic malignancies remain unclear. In a retrospective study, we compared allogeneic PBSCT (n = 30) with BMT (n = 110) in children with acute leukemia between January 2001 and September 2006.


Nuclear Instruments & Methods in Physics Research Section A-accelerators Spectrometers Detectors and Associated Equipment | 2003

New evidence of dominant processing effects in standard and oxygenated silicon diodes after neutron irradiation

A. Candelori; R. Rando; D. Bisello; F. Campabadal; V. Cindro; L. Fonseca; A. Kaminski; A. Litovchenko; M. Lozano; Caridad Martinez; A. Moreno; J.M. Rafí; J. Santander; M. Ullan; J. Wyss

Abstract Silicon diodes processed on standard and oxygenated silicon substrates by three different manufacturers have been irradiated by neutrons in a nuclear reactor. The leakage current density ( J D ) increase is linear with the neutron fluence. J D and its annealing curve at 80°C do not present any sizeable dependence on substrate oxygenation and/or manufacturing process. The acceptor introduction rate ( β ) of the effective substrate doping concentration ( N eff ) is independent from the oxygen concentration when standard and oxygenated devices from the same manufacturer are considered. On the contrary, β significantly varies from one manufacturer to another showing that the β dependence on the particular process can be important, overtaking the small substrate oxygenation effect. Finally, the average saturation value of the N eff reverse annealing is slightly lower for the oxygenated samples, pointing out a positive effect of the substrate oxygenation even for devices irradiated by neutrons.

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Robert A. Krance

Center for Cell and Gene Therapy

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Helen E. Heslop

Center for Cell and Gene Therapy

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Malcolm K. Brenner

Center for Cell and Gene Therapy

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Ann M. Leen

Center for Cell and Gene Therapy

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Catherine M. Bollard

Center for Cell and Gene Therapy

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Kathryn Leung

Center for Cell and Gene Therapy

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Lisa R. Forbes

Baylor College of Medicine

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Cliona M. Rooney

Center for Cell and Gene Therapy

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