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1.
Blood ; 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31942610

RESUMO

Viral infections are common and are potentially life-threatening in patients with moderate to severe primary immunodeficiency disorders. Since T-cell immunity contributes to the control of many viral pathogens, adoptive immunotherapy with virus-specific T-cells has been a logical and effective way of combating severe viral disease in immunocompromised patients in multiple phase I and II clinical trials. Common viral targets include cytomegalovirus, Epstein-Barr virus, and adenovirus, though recent published studies have successfully targeted additional pathogens, including HHV6, BK virus and JC virus. Though most studies have utilized VSTs derived from allogenic stem cell donors, the use of banked VSTs derived from partially HLA-matched donors has shown efficacy in multi-center settings. Hence, this approach could shorten the time for patients to receive VST therapy thus improving accessibility. In this review, we discuss the usage of VSTs for patients with PID in clinical trials, as well as future potential targets and methods to broaden the applicability of virus-directed T-cell immunotherapy for this vulnerable patient population.

2.
J Allergy Clin Immunol ; 145(1): 46-69, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31568798

RESUMO

Genetic testing has become an integral component of the diagnostic evaluation of patients with suspected primary immunodeficiency diseases. Results of genetic testing can have a profound effect on clinical management decisions. Therefore clinical providers must demonstrate proficiency in interpreting genetic data. Because of the need for increased knowledge regarding this practice, the American Academy of Allergy, Asthma & Immunology Primary Immunodeficiency Diseases Committee established a work group that reviewed and summarized information concerning appropriate methods, tools, and resources for evaluating variants identified by genetic testing. Strengths and limitations of tests frequently ordered by clinicians were examined. Summary statements and tables were then developed to guide the interpretation process. Finally, the need for research and collaboration was emphasized. Greater understanding of these important concepts will improve the diagnosis and management of patients with suspected primary immunodeficiency diseases.

3.
Transfusion ; 60(1): 7-10, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31469438

RESUMO

Virus-specific T cells allow targeting of multiple pathogens in patients after hematopoietic stem cell transplantation and have demonstrated potential efficacy for cytomegalovirus, Epstein-Barr Virus, and adenovirus. Novel targets may include BK virus, JC virus, varicella zoster virus, human herpesvirus 6, Aspergillus, human parainfluenza virus-3, herpes simplex virus Type I, Zika virus, and mycobacteria. Generation of patient-specific products and third-party products may expand feasibility of therapy.

4.
Pediatr Blood Cancer ; 67(3): e28126, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31850668

RESUMO

Children with ataxia telangiectasia (AT), a primary immunodeficiency caused by mutations in ATM, which is critical for repairing DNA defects, are at risk for the development of hematologic malignancy, frequently driven by infection with Epstein-Barr virus (EBV). Conventional chemotherapy is poorly tolerated by patients with AT, with excessive toxicity even when doses are reduced. Here, we report on two patients with AT and EBV-positive neoplasms who were treated with EBV-targeted viral-specific T cells (VST). One patient had a prolonged complete response to VSTs while the other had a partial response. Therapy was well tolerated without infusion toxicity or graft-versus-host disease.

5.
J Infect Dis ; 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31562500

RESUMO

BACKGROUND: Chronic norovirus infection in immunocompromised patients can be severe, and presently there is no effective treatment. Adoptive transfer of virus-specific T-cells has proven to be safe and effective for the treatment of many viral infections, and could represent a novel treatment approach for chronic norovirus infection. Hence, we sought to generate human norovirus-specific T-cells (NSTs) that can recognize different viral sequences. METHODS: NSTs were generated from peripheral blood of healthy donors by stimulation with overlapping peptide libraries spanning the entire coding sequence of the norovirus genome. RESULTS: We successfully generated T-cells targeting multiple norovirus antigens with a mean 4.2 ± 0.5-fold expansion after 10 days. NSTs were comprised of both CD4+ and CD8+ T-cells that expressed markers for central memory and effector memory phenotype with minimal expression of co-inhibitory molecules, and were polyfunctional based on cytokine production. We identified novel CD4 and CD8-restricted immunodominant epitopes within NS6 and VP1 antigens. Furthermore, NSTs showed a high degree of cross-reactivity to multiple variant epitopes from clinical isolates. CONCLUSIONS: Our findings identify immunodominant human norovirus T-cell epitopes and demonstrate that it is feasible to generate potent NSTs from third party donors for use in antiviral immunotherapy.

6.
Blood Adv ; 3(14): 2057-2068, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31292125

RESUMO

Adoptive transfer of virus-specific T cells (VSTs) has been shown to be safe and effective in stem cell transplant recipients. However, the lack of virus-experienced T cells in donor cord blood (CB) has prevented the development of ex vivo expanded donor-derived VSTs for recipients of this stem cell source. Here we evaluated the feasibility and safety of ex vivo expansion of CB T cells from the 20% fraction of the CB unit in pediatric patients receiving a single CB transplant (CBT). In 2 clinical trials conducted at 2 separate sites, we manufactured CB-derived multivirus-specific T cells (CB-VSTs) targeting Epstein-Barr virus (EBV), adenovirus, and cytomegalovirus (CMV) for 18 (86%) of 21 patients demonstrating feasibility. Manufacturing for 2 CB-VSTs failed to meet lot release because of insufficient cell recovery, and there was 1 sterility breach during separation of the frozen 20% fraction. Delayed engraftment was not observed in patients who received the remaining 80% fraction for the primary CBT. There was no grade 3 to 4 acute graft-versus-host disease (GVHD) associated with the infusion of CB-VSTs. None of the 7 patients who received CB-VSTs as prophylaxis developed end-organ disease from CMV, EBV, or adenovirus. In 7 patients receiving CB-VSTs for viral reactivation or infection, only 1 patient developed end-organ viral disease, which was in an immune privileged site (CMV retinitis) and occurred after steroid therapy for GVHD. Finally, we demonstrated the long-term persistence of adoptively transferred CB-VSTs using T-cell receptor-Vß clonotype tracking, suggesting that CB-VSTs are a feasible addition to antiviral pharmacotherapy.

7.
Cytotherapy ; 21(8): 840-855, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31279695

RESUMO

BACKGROUND: Zika virus (ZIKV) infection can cause severe birth defects in newborns with no effective currently available treatment. Adoptive transfer of virus-specific T cells has proven to be safe and effective for the prevention or treatment of many viral infections, and could represent a novel treatment approach for patients with ZIKV infection. However, extending this strategy to the ZIKV setting has been hampered by limited data on immunogenic T-cell antigens within ZIKV. Hence, we have generated ZIKV-specific T cells and characterized the cellular immune responses against ZIKV antigens. METHODS: T-cell products were generated from peripheral blood of ZIKV-exposed donors, ZIKV-naive adult donors and umbilical cord blood by stimulation with pentadecamer (15mer) overlapping peptide libraries spanning four ZIKV polyproteins (C, M, E and NS1) using a Good Manufacturing Practice-compliant protocol. RESULTS: We successfully generated T cells targeting ZIKV antigens with clinically relevant numbers. The ex vivo-expanded T cells comprised both CD4+ and CD8+ T cells that were able to produce Th1-polarized effector cytokines and kill ZIKV-infected HLA-matched monocytes, confirming functionality of this unique T-cell product as a potential "off-the-shelf" therapeutic. Epitope mapping using peptide arrays identified several novel HLA class I and class II-restricted epitopes within NS1 antigen, which is essential for viral replication and immune evasion. DISCUSSION: Our findings demonstrate that it is feasible to generate potent ZIKV-specific T cells from a variety of cell sources including virus naïve donors for future clinical use in an "off-the-shelf" setting.

8.
F1000Res ; 8: 2, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249677

RESUMO

A patient with WHIM syndrome immunodeficiency presented with sudden painless right eye blindness associated with advanced retinal and optic nerve damage. Toxoplasma gondii was detected by PCR in vitreous fluid but not serum.  The patient was treated with pyrimethamine/sulfadiazine for 6 weeks due to evidence of active ocular inflammation and then received prophylaxis with trimethoprim-sulfamethoxazole due to his immunosuppression.  Vision did not return; however, the infection did not spread to involve other sites.  Toxoplasmosis is rare in primary immunodeficiency disorders and is the first protozoan infection reported in WHIM syndrome.

9.
Br J Haematol ; 187(2): 206-218, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31219185

RESUMO

Viral infections are a serious cause of morbidity and mortality following haematopoietic stem cell transplantation (HSCT). Adoptive cellular therapy with virus-specific T cells (VSTs) has been successful in preventing or treating targeted viruses in prior studies, but the composition of ex vivo expanded VST and the critical cell populations that mediate antiviral activity in vivo are not well defined. We utilized deep sequencing of the T-cell receptor beta chain (TCRB) in order to classify and track VST populations in 12 patients who received VSTs following HSCT to prevent or treat viral infections. TCRB sequencing was performed on sorted VST products and patient peripheral blood mononuclear cells samples. TCRB diversity was gauged using the Shannon entropy index, and repertoire similarity determined using the Morisita-Horn index. Similarity indices reflected an early change in TCRB diversity in eight patients, and TCRB clonotypes corresponding to targeted viral epitopes expanded in eight patients. TCRB repertoire diversity increased in nine patients, and correlated with cytomegalovirus (CMV) viral load following VST infusion (P = 0·0071). These findings demonstrate that allogeneic VSTs can be tracked via TCRB sequencing, and suggests that T-cell receptor repertoire diversity may be critical for the control of CMV reactivation after HSCT.

10.
J Exp Med ; 216(9): 2038-2056, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31217193

RESUMO

Autosomal recessive IRF7 and IRF9 deficiencies impair type I and III IFN immunity and underlie severe influenza pneumonitis. We report three unrelated children with influenza A virus (IAV) infection manifesting as acute respiratory distress syndrome (IAV-ARDS), heterozygous for rare TLR3 variants (P554S in two patients and P680L in the third) causing autosomal dominant (AD) TLR3 deficiency. AD TLR3 deficiency can underlie herpes simplex virus-1 (HSV-1) encephalitis (HSE) by impairing cortical neuron-intrinsic type I IFN immunity to HSV-1. TLR3-mutated leukocytes produce normal levels of IFNs in response to IAV. In contrast, TLR3-mutated fibroblasts produce lower levels of IFN-ß and -λ, and display enhanced viral susceptibility, upon IAV infection. Moreover, the patients' iPSC-derived pulmonary epithelial cells (PECs) are susceptible to IAV. Treatment with IFN-α2b or IFN-λ1 rescues this phenotype. AD TLR3 deficiency may thus underlie IAV-ARDS by impairing TLR3-dependent, type I and/or III IFN-mediated, PEC-intrinsic immunity. Its clinical penetrance is incomplete for both IAV-ARDS and HSE, consistent with their typically sporadic nature.

11.
Front Immunol ; 10: 621, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984189

RESUMO

Mycobacterial Infections can be severe in patients with T-cell deficiency or phagocyte disorders, and treatment is frequently complicated by antimicrobial resistance. Restoration of T-cell immunity via stem cell transplantation facilitates control of mycobacterial infections, but presence of active infections during transplantation is associated with a higher risk of mortality. Adoptive T cell immunotherapy has been successful in targeting viruses, but has not been attempted to treat mycobacterial infections. We sought to expand and characterize mycobacterial-specific T-cells derived from healthy donors in order to determine suitability for adoptive immunotherapy. Mycobacteria-specific T-cells (MSTs) were generated from 10 healthy donors using a rapid ex vivo expansion protocol targeting five known mycobacterial target proteins (AG85B, PPE68, ESXA, ESXB, and ADK). MSTs were compared to T-cells expanded from the same donors using lysate from M. tuberculosis or purified protein derivative from M. avium (sensitin). MST expansion from seven patients with primary immunodeficiency disorders (PID) and two patients with IFN-γ autoantibodies and invasive M. avium infections. MSTs expanded from healthy donors recognized a median of 3 of 5 antigens, with production of IFN-γ, TNF, and GM-CSF in CD4+ T cells. Comparison of donors who received BCG vaccine (n = 6) to those who did not (n = 4) showed differential responses to PPE68 (p = 0.028) and ADK (p = 0.015) by IFN-γ ELISpot. MSTs expanded from lysate or sensitin also recognized multiple mycobacterial antigens, with a statistically significant differences noted only in the response to PPE68 (p = 0.016). MSTs expanded from patients with primary immunodeficiency (PID) and invasive mycobacterial infections showed activity against mycobacterial antigens in only two of seven subjects, whereas both patients with IFN-γ autoantibodies recognized mycobacterial antigens. Thus, MSTs can be generated from donors using a rapid expansion protocol regardless of history of BCG immunization. Most tested PID patients had no detectable T-cell immunity to mycobacteria despite history of infection. MSTs may have clinical utility for adoptive immunotherapy in T-cell deficient patients with invasive mycobacterial infections.

12.
J Allergy Clin Immunol Pract ; 7(3): 809-818, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30581131

RESUMO

Viral infections are common and can be potentially fatal in patients with primary immunodeficiency disorders (PIDDs). Because viral susceptibility stems from poor to absent T-cell function in most patients with moderate to severe forms of PIDD, adoptive immunotherapy with virus-specific T cells (VSTs) has been used to combat viral infections in the setting of hematopoietic stem cell transplantation in multiple clinical trials. Most trials to date have targeted cytomegalovirus, EBV, and adenovirus either alone or in combination, although newer trials have expanded the number of targeted pathogens. Use of banked VSTs produced from third-party donors has also been studied as a method of expanding access to this therapy. Here we review the clinical experience with VST therapy for patients with PIDDs as well as future potential targets and approaches for the use of VSTs to improve clinical outcomes for this specific patient population.

14.
J Clin Immunol ; 38(7): 804-809, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30267241

RESUMO

PURPOSE: Patients with primary immunodeficiency diseases (PID) are perceived to be at high risk for acquiring as well as developing complications from infections. There is little data describing the infection type and frequency these patients may acquire in the community or during hospital admissions. Data is critically needed in order to inform best practices on how to protect these vulnerable patients. METHODS: This is a retrospective study which included PID patients who were discharged from Children's National Health System (CNHS) from January 1, 2011, through August 31, 2017, and were assigned a discharge diagnosis code indicating PID. Hospitalizations that occurred in the study period were reviewed to extract information on the type of infections upon admission and during hospitalization. The rate of hospital acquired infections (HAIs) was calculated by the number of HAIs divided by the total number of days between date of admission and date of discharge or receiving the first bone marrow transplant, whichever the one came first. The rates were then compared to the HAI rate among oncology patients receiving treatment at CNHS during the same study period. RESULTS: During this study period, 33 PID patients were admitted 80 times for a total of 1855 patient days. Of these 80 admissions, 31 were due to an infection. Ten of the 31 admissions with severe combined immunodeficiency disease (SCID) were infection related, 4/4 in ectodermal dysplasia with immunodeficiency due to gain of function mutation (IkappaBalpha) patients, 8/10 in Wiskott-Aldrich patients, 1/2 in STAT3 mutation patients, 1/1 in Hyper IGM patient, 1/5 in severe chronic active EBV (SCAEBV) patients, 1/1 NK defect, 2/21 in primary hemophagocytic lymphohistiocytosis patients, 3/4 chronic granulomatous disease, and 0/1 congenital neutropenia. HAI occurred in 11 out of 80 admissions (13.75%). Patients with SCID had the highest HAI rate of 13.09 per 1000 patient days, followed by SCAEBV (11.10), IkappaBalpha (6.58), and Wiskott-Aldrich (4.91). Comparing to oncology patients in which the HAI rate was 0.92 per 1000 patient days. SCID patients had 11.7 (95% confidence interval 3.7-29; p < 0.001) and T cell defects excluding SCID had 4.8 (95% CI 1.0-14.8; p = 0.03) times greater risk of acquiring an infection during a hospitalization. CONCLUSIONS: Patients with severe T cell defects such as SCID are at greater risk for infections in the community and in hospital settings. Additional infection prevention measures are likely needed when caring for these patients in a clinic or as an inpatient. Further studies are urgently needed to determine the most appropriate measures for these patients.


Assuntos
Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/etiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/etiologia , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/epidemiologia , Biomarcadores , Infecções Comunitárias Adquiridas/prevenção & controle , Infecção Hospitalar/prevenção & controle , Suscetibilidade a Doenças , Hospitalização , Humanos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
15.
Blood ; 132(17): 1737-1749, 2018 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-30154114

RESUMO

The Primary Immune Deficiency Treatment Consortium (PIDTC) performed a retrospective analysis of 662 patients with severe combined immunodeficiency (SCID) who received a hematopoietic cell transplantation (HCT) as first-line treatment between 1982 and 2012 in 33 North American institutions. Overall survival was higher after HCT from matched-sibling donors (MSDs). Among recipients of non-MSD HCT, multivariate analysis showed that the SCID genotype strongly influenced survival and immune reconstitution. Overall survival was similar for patients with RAG, IL2RG, or JAK3 defects and was significantly better compared with patients with ADA or DCLRE1C mutations. Patients with RAG or DCLRE1C mutations had poorer immune reconstitution than other genotypes. Although survival did not correlate with the type of conditioning regimen, recipients of reduced-intensity or myeloablative conditioning had a lower incidence of treatment failure and better T- and B-cell reconstitution, but a higher risk for graft-versus-host disease, compared with those receiving no conditioning or immunosuppression only. Infection-free status and younger age at HCT were associated with improved survival. Typical SCID, leaky SCID, and Omenn syndrome had similar outcomes. Landmark analysis identified CD4+ and CD4+CD45RA+ cell counts at 6 and 12 months post-HCT as biomarkers predictive of overall survival and long-term T-cell reconstitution. Our data emphasize the need for patient-tailored treatment strategies depending upon the underlying SCID genotype. The prognostic significance of CD4+ cell counts as early as 6 months after HCT emphasizes the importance of close follow-up of immune reconstitution to identify patients who may need additional intervention to prevent poor long-term outcome.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Transplante de Células-Tronco Hematopoéticas , Reconstituição Imune/imunologia , Imunodeficiência Combinada Severa/genética , Imunodeficiência Combinada Severa/mortalidade , Imunodeficiência Combinada Severa/terapia , Genótipo , Humanos , Contagem de Linfócitos , Estudos Retrospectivos
16.
Biol Blood Marrow Transplant ; 24(9): 1944-1946, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29753156

RESUMO

Viral infections can be life threatening in patients with severe combined immunodeficiency (SCID) and other forms of profound primary immunodeficiency disorders both before and after hematopoietic stem cell transplantation (HSCT). Adoptive immunotherapy with virus-specific T cells (VSTs) has been utilized in many patients in the setting of HSCT, but has very rarely been attempted for treatment of viral infections before HSCT. Here we describe the use of VSTs in an infant with RAG1 SCID who had developed disseminated adenovirus which failed to improve on cidofovir. Adenovirus cleared following 2 doses of VSTs and marrow infusion from a matched unrelated donor, without incidence of graft versus host disease. T cell receptor-b sequencing demonstrated expansion of adenovirus-specific T cell fraction of the VSTs, suggesting that infusion facilitated viral clearance. This report suggests that VSTs are likely safe in the pre-HSCT period, and may be a useful bridge therapy for infants with SCID and persistent viral infections.


Assuntos
Adenoviridae/patogenicidade , Antivirais/uso terapêutico , Imunodeficiência Combinada Severa/terapia , Viroses/virologia , Antivirais/farmacologia , Feminino , Humanos , Lactente , Masculino , Imunodeficiência Combinada Severa/patologia
18.
J Pediatric Infect Dis Soc ; 7(suppl_1): S40-S44, 2018 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-29746676

RESUMO

Chronic granulomatous disease is a rare and potentially fatal disorder of neutrophil function. Beyond current medical management and hematopoietic stem cell transplantation, new methods of gene therapy that use lentiviral vectors or gene editing might extend curative therapies to patients who lack a suitable transplantation donor while eliminating the risk of graft-versus-host disease. Furthermore, new therapies focused on altering the biology of phagolysosomes might offer novel targeted treatments for inflammatory complications in patients with chronic granulomatous disease.


Assuntos
Terapia Genética , Doença Granulomatosa Crônica/terapia , Vetores Genéticos , Doença Granulomatosa Crônica/genética , Humanos , Lentivirus , Mutação com Perda de Função
19.
Front Immunol ; 9: 556, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29616044

RESUMO

Patients with primary immunodeficiency disorders (PID) have an increased risk from acute and chronic Epstein-Barr Virus (EBV) viral infections and EBV-associated malignancies. Hematopoietic stem cell transplantation (HSCT) is a curative strategy for many patients with PID, but EBV-related complications are common in the immediate post-transplant period due to delayed reconstitution of T cell immunity. Adoptive T cell therapy with EBV-specific T cells is a promising therapeutic strategy for patients with PID both before and after HSCT. Here we review the methods used to manufacture EBV-specific T cells, the clinical outcomes, and the ongoing challenges for future development of the strategy.


Assuntos
Transferência Adotiva/métodos , Infecções por Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4/imunologia , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/terapia , Linfócitos T/imunologia , Antígenos Virais/imunologia , Proliferação de Células , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Transplante de Células-Tronco Hematopoéticas/métodos , Herpesvirus Humano 4/fisiologia , Humanos , Síndromes de Imunodeficiência/complicações , Linfócitos T/transplante
20.
Cytotherapy ; 20(3): 385-393, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29331266

RESUMO

Human papilloma virus (HPV) is a known cause of cervical cancer, squamous cell carcinoma and laryngeal cancer. Although treatments exist for HPV-associated malignancies, patients unresponsive to these therapies have a poor prognosis. Recent findings from vaccine studies suggest that T-cell immunity is essential for disease control. Because Epstein-Barr Virus (EBV)-specific T cells have been highly successful in treating or preventing EBV-associated tumors, we hypothesized that the development of a manufacturing platform for HPV-specific T cells from healthy donors could be used in a third-party setting to treat patients with high-risk/relapsed HPV-associated cancers. Most protocols for generating virus-specific T cells require prior exposure of the donor to the targeted virus and, because the seroprevalence of high-risk HPV types varies greatly by age and ethnicity, manufacturing of donor-derived HPV-specific T cells has proven challenging. We, therefore, made systematic changes to our current Good Manufacturing Practice (GMP)-compliant protocols to improve antigen presentation, priming and expansion for the manufacture of high-efficacy HPV-specific T cells. Like others, we found that current methodologies fail to expand HPV-specific T cells from most healthy donors. By optimizing dendritic cell maturation and function with lipopolysaccharide (LPS) and interferon (IFN)γ, adding interleukin (IL)-21 during priming and depleting memory T cells, we achieved reliable expansion of T cells specific for oncoproteins E6 and E7 to clinically relevant amounts (mean, 578-fold expansion; n = 10), which were polyfunctional based on cytokine multiplex analysis. In the third-party setting, such HPV-specific T-cell products might serve as a potent salvage therapy for patients with HPV-associated diseases.


Assuntos
Imunoterapia/métodos , Papillomaviridae/imunologia , Linfócitos T/imunologia , Células Cultivadas , Células Dendríticas/imunologia , Células Dendríticas/virologia , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Hospedeiro Imunocomprometido , Interferon gama/farmacologia , Interleucinas/farmacologia , Antígenos Comuns de Leucócito/metabolismo , Lipopolissacarídeos/farmacologia , Proteínas Oncogênicas Virais/farmacologia , Proteínas E7 de Papillomavirus/farmacologia , Proteínas Repressoras/farmacologia , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/fisiologia
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