Publications by authors named "Jessica Markby"

13 Publications

  • Page 1 of 1

Feasibility, effectiveness and cost of a decentralized HCV care model among the general population in Delhi, India.

Liver Int 2021 Nov 24. Epub 2021 Nov 24.

FIND, Geneva, Switzerland.

Background And Aims: India has a significant burden of hepatitis C virus (HCV) infection and has committed to achieving national elimination by 2030. This will require a substantial scale-up in testing and treatment. The "HEAD-Start Project Delhi" aimed to enhance HCV diagnosis and treatment pathways among the general population.

Methods: A prospective study was conducted at 5 district hospitals (Arm 1: one-stop shop), 15 polyclinics (Arm 2: referral for viral load (VL) testing and treatment) and 62 screening camps (Arm 3: referral for treatment). HCV prevalence, retention in the HCV care cascade, and turn-around time were measured.

Results: Between January and September 2019, 37 425 participants were screened for HCV. The median (IQR) age of participants was 35 (26-48) years, with 50.4% male and 49.6% female. A significantly higher proportion of participants in Arm 1 (93.7%) and Arm 3 (90.3%) received a VL test compared with Arm 2 (52.5%, P < .001). Of those confirmed positive, treatment was initiated at significantly higher rates for participants in both Arms 1 (85.6%) and 2 (73.7%) compared to Arm 3 (41.8%, P < .001). Arm 1 was found to be a cost-saving strategy compared to Arm 2, Arm 3, and no action.

Conclusions: Delivery of all services at a single site (district hospitals) resulted in a higher yield of HCV seropositive cases and retention compared with sites where participants were referred elsewhere for VL testing and/or treatment. The highest level of retention in the care cascade was also associated with the shortest turn-around times.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.15112DOI Listing
November 2021

Diagnostic accuracy of dried plasma spot specimens for HIV-1 viral load testing: a systematic review and meta-analysis.

J Acquir Immune Defic Syndr 2021 Nov 2. Epub 2021 Nov 2.

Fred Hutchinson Cancer Research Center, Seattle, Washington; Clinton Health Access Initiative, Boston, Massachusetts; National Center for Global Health, Istituto Superiore di Sanita, Rome, Italy; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington; Laboratory of Virology, University Hospital of Saint-Etienne, France; RTI International, Rockville, Maryland; Departments of Pediatrics and Laboratory Medicine, University of Washington, Seattle, Washington; Unidad de Investigacion Medica en Enfermedades Infecciosas y Parasitarias, UMAE Hospital de Pediatria, CMN Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico; Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC; Department of Human Retrovirology, University of Amsterdam, Amsterdam, The Netherlands; Laboratory of Virology, University Hospital of Bordeaux 33076, Bordeaux, France; University of California San Diego, La Jolla, California; Division of Global HIV/AIDS, US Centers for Disease Control and Prevention, Windhoek, Namibia; St. Stephens AIDS Trust, Chelsea & Westminster Hospital, London, UK; International Laboratory Branch, Division of Global HIV/AIDS and TB, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia; Division of HIV/AIDS Prevention, US Centers for Disease Control and Prevention, Kisumu, Kenya; World Health Organization, Geneva, Switzerland.

Background: Dried plasma spot specimens may be a viable alternative to traditional liquid plasma in field settings, but the diagnostic accuracy is not well understood.

Methods: Standard databases (PubMed and Medline), conferences, and grey literature were searched until January 2019. The quality of evidence was evaluated using STARD and QUADAS-2 criteria. We used univariate and bivariate random effects models to determine misclassification, sensitivity, and specificity across multiple thresholds, overall and for each viral load technology and to account for between-study variation.

Results: We identified 23 studies for inclusion in the systematic review that compared the diagnostic accuracy of dried plasma spots to plasma. Primary data from 16 of the 23 studies were shared and included in the meta-analysis, representing 18 countries, totaling 1,847 paired dried plasma spot:plasma data points. The mean bias of dried plasma spot specimens compared to plasma was 0.28 log10 copies/ml, while the difference in median viral load was 2.25 log10 copies/ml. More dried plasma spot values were undetectable compared to plasma values (43.6% vs. 29.8%). Analyzing all technologies together, the sensitivity and specificity of dried plasma spot specimens was >92% across all treatment failure thresholds compared and total misclassification <5.4% across all treatment failure thresholds compared. Some technologies had lower sensitivity or specificity; however, the results were typically consistent across treatment failure thresholds.

Discussion: Overall, dried plasma spot specimens performed relatively well compared to plasma with sensitivity and specificity values greater than 90% and misclassification rates less than 10% across all treatment failure thresholds reviewed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAI.0000000000002855DOI Listing
November 2021

Outcomes of the CT2 study: A 'one-stop-shop' for community-based hepatitis C testing and treatment in Yangon, Myanmar.

Liver Int 2021 11 10;41(11):2578-2589. Epub 2021 Jul 10.

Disease Elimination Program, Burnet Institute, Melbourne, Australia.

Background: With the advent of low-cost generic direct-acting antivirals (DAA), hepatitis C (HCV) elimination is now achievable even in low-/middle-income settings. We assessed the feasibility and effectiveness of a simplified clinical pathway using point-of-care diagnostic testing and non-specialist-led care in a decentralized, community-based setting.

Methods: This feasibility study was conducted at two sites in Yangon, Myanmar: one for people who inject drugs (PWID), and the other for people with liver disease. Participants underwent on-site rapid anti-HCV testing and HCV RNA testing using GeneXpert . General practitioners determined whether participants started DAA therapy immediately or required specialist evaluation. Primary outcome measures were progression through the HCV care cascade, including uptake of RNA testing and treatment, and treatment outcomes.

Findings: All 633 participants underwent anti-HCV testing; 606 (96%) were anti-HCV positive and had HCV RNA testing. Of 606 tested, 535 (88%) were RNA positive and had pre-treatment assessments; 30 (6%) completed specialist evaluation. Of 535 RNA positive participants, 489 (91%) were eligible to initiate DAAs, 477 (98%) completed DAA therapy and 421 achieved SVR12 (92%; 421/456). Outcomes were similar by site: PWID site: 91% [146/161], and liver disease site: 93% [275/295]). Compensated cirrhotic patients were treated in the community; they achieved an SVR12 of 83% (19/23). Median time from RNA test to DAA initiation was 3 days (IQR 2-5).

Conclusions: Delivering a simplified, non-specialist-led HCV treatment pathway in a decentralized community setting was feasible in Yangon, Myanmar; retention in care and treatment success rates were very high. This care model could be integral in scaling up HCV services in Myanmar and other low- and middle-income settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.14983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8596916PMC
November 2021

Systematic review of the accuracy of plasma preparation tubes for HIV viral load testing.

PLoS One 2019 21;14(11):e0225393. Epub 2019 Nov 21.

World Health Organization, Geneva, Switzerland.

Expanding access to HIV viral load testing is essential to improving the care and treatment of people living with HIV/AIDS and ending the AIDS epidemic. Though significant investments have been made in the past five years, many high burden, low resource countries continue to have viral load access rates below 50%. Plasma preparation tubes (PPTs) can simplify storage, transport, and preparation of plasma used for viral load testing. A systematic review was conducted to evaluate the accuracy of plasma preparation tubes for HIV viral load testing. Study results regarding the accuracy of PPT viral load measurements across various storage and transportation conditions were examined. The quality of evidence was evaluated using GRADE and QUADAS-2 criteria. The review identified 16 studies using PPTs with data from 6,141 individuals from 1995 to 2014. Overall the quality of evidence was rated as moderate, with unclear applicability for studies evaluating viral load assays that are no longer commercially available. Significantly elevated viral load results (>0.3 log copies/ml difference) have been observed with PPTs; however, when manufacturer handling instructions are followed, when plasma is aliquoted into a secondary tube, or when PPTs are centrifuged prior to testing, PPT results only differed from standard EDTA plasma testing using commercially available viral load assays by a range on average of -0.03 to +0.08 log copies/ml across studies. Although spuriously elevated viral load results have been observed with PPTs, following proper sample handing techniques have been shown to provide accurate results. PPTs, therefore, provide a high quality alternative specimen type for countries seeking solutions to infrastructure and specimen transportation challenges in an effort to scale-up viral load testing and achieve 90-90-90 targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225393PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874077PMC
March 2020

Performance of non-laboratory staff for diagnostic testing and specimen collection in HIV programs: A systematic review and meta-analysis.

PLoS One 2019 2;14(5):e0216277. Epub 2019 May 2.

World Health Organization, Geneva, Switzerland.

Background: In most high HIV burden countries, many HIV patients do not have reliable access to required diagnostic laboratory tests. Task shifting of clinical tasks to lower cadres of health care workers and lay counselors has been successful in scaling up treatment for HIV and may also be an effective strategy in expanding access to essential diagnostic testing.

Methods: We screened major electronic databases between 1 January 2005 to 26 August 2018 to identify studies assessing ease of use and accuracy of task shifting of HIV-related diagnostic testing and/or specimen collection to non-laboratory health staff. Two independent reviewers screened all titles and abstracts for studies that analyzed diagnostic accuracy, patient impact, ease-of-use, or cost-effectiveness. Studies were assessed for quality, bias, and applicability following the QUADAS-2 framework. We generated summary estimates using random-effects meta-analyses.

Results: We identified 42 relevant studies. Overall, point-of-care CD4 testing performed by non-laboratory staff had a mean bias of -54.44 (95% CI: -72.40 --36.48) compared to conventional laboratory-based. Though studies were limited, the diagnostic accuracy of point-of-care alanine transaminase enzyme (ALT) and hemoglobin testing performed by non-laboratory staff was comparable to conventional laboratory-based testing by laboratory professionals. Point-of-care testing and/or specimen collection were generally found to be acceptable and easy to use for non-laboratory staff.

Conclusions: Task shifting of testing using point-of-care technologies to non-laboratory staff was comparable to laboratory professionals operating the same technology in the laboratory. Some variability was observed comparing the performance of point-of-care CD4 testing by non-laboratory staff to conventional laboratory-based technologies by laboratory professionals indicating potential lower performance was likely technological rather than operator caused. The benefits of task shifting of testing may outweigh any possible harms as task shifting allows for increased decentralization, access of specific diagnostics, and faster result delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0216277PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497381PMC
January 2020

Impact of SMS/GPRS Printers in Reducing Time to Early Infant Diagnosis Compared With Routine Result Reporting: A Systematic Review and Meta-Analysis.

J Acquir Immune Defic Syndr 2017 12;76(5):522-526

*Clinton Health Access Initiative, Boston, MA; and †World Health Organization, Geneva, Switzerland.

Background: Despite significant gains made toward improving access, early infant diagnosis (EID) testing programs suffer from long test turnaround times that result in substantial loss to follow-up and mortality associated with delays in antiretroviral therapy initiation. These delays in treatment initiation are particularly impactful because of significant HIV-related infant mortality observed by 2-3 months of age. Short message service (SMS) and general packet radio service (GPRS) printers allow test results to be transmitted immediately to health care facilities on completion of testing in the laboratory.

Methods: We conducted a systematic review and meta-analysis to assess the benefit of using SMS/GPRS printers to increase the efficiency of EID test result delivery compared with traditional courier paper-based results delivery methods.

Results: We identified 11 studies contributing data for over 16,000 patients from East and Southern Africa. The test turnaround time from specimen collection to result received at the health care facility with courier paper-based methods was 68.0 days (n = 6835), whereas the test turnaround time with SMS/GPRS printers was 51.1 days (n = 6711), resulting in a 2.5-week (25%) reduction in the turnaround time.

Conclusions: Courier paper-based EID test result delivery methods are estimated to add 2.5 weeks to EID test turnaround times in low resource settings and increase the risk that infants receive test results during or after the early peak of infant mortality. SMS/GPRS result delivery to health care facility printers significantly reduced test turnaround time and may reduce this risk. SMS/GPRS printers should be considered for expedited delivery of EID and other centralized laboratory test results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QAI.0000000000001526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5690299PMC
December 2017

High Levels of Transmitted HIV Drug Resistance in a Study in Papua New Guinea.

PLoS One 2017 1;12(2):e0170265. Epub 2017 Feb 1.

Division of Geographic Medicine and Infection Disease, Tufts Medical Center, Boston, Massachusetts, United States of America.

Introduction: Papua New Guinea is a Pacific Island nation of 7.3 million people with an estimated HIV prevalence of 0.8%. ART initiation and monitoring are guided by clinical staging and CD4 cell counts, when available. Little is known about levels of transmitted HIV drug resistance in recently infected individuals in Papua New Guinea.

Methods: Surveillance of transmitted HIV drug resistance in a total of 123 individuals recently infected with HIV and aged less than 30 years was implemented in Port Moresby (n = 62) and Mount Hagen (n = 61) during the period May 2013-April 2014. HIV drug resistance testing was performed using dried blood spots. Transmitted HIV drug resistance was defined by the presence of one or more drug resistance mutations as defined by the World Health Organization surveillance drug resistance mutations list.

Results: The prevalence of non-nucleoside reverse transcriptase inhibitor transmitted HIV drug resistance was 16.1% (95% CI 8.8%-27.4%) and 8.2% (95% CI 3.2%-18.2%) in Port Moresby and Mount Hagen, respectively. The prevalence of nucleoside reverse transcriptase inhibitor transmitted HIV drug resistance was 3.2% (95% CI 0.2%-11.7%) and 3.3% (95% CI 0.2%-11.8%) in Port Moresby and Mount Hagen, respectively. No protease inhibitor transmitted HIV drug resistance was observed.

Conclusions: The level of non-nucleoside reverse transcriptase inhibitor drug resistance in antiretroviral drug naïve individuals recently infected with HIV in Port Moresby is amongst the highest reported globally. This alarming level of transmitted HIV drug resistance in a young sexually active population threatens to limit the on-going effective use of NNRTIs as a component of first-line ART in Papua New Guinea. To support the choice of nationally recommended first-line antiretroviral therapy, representative surveillance of HIV drug resistance among antiretroviral therapy initiators in Papua New Guinea should be urgently implemented.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0170265PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5287486PMC
August 2017

POC CD4 Testing Improves Linkage to HIV Care and Timeliness of ART Initiation in a Public Health Approach: A Systematic Review and Meta-Analysis.

PLoS One 2016 13;11(5):e0155256. Epub 2016 May 13.

Clinton Health Access Initiative, Boston, MA, United States of America.

Background: CD4 cell count is an important test in HIV programs for baseline risk assessment, monitoring of ART where viral load is not available, and, in many settings, antiretroviral therapy (ART) initiation decisions. However, access to CD4 testing is limited, in part due to the centralized conventional laboratory network. Point of care (POC) CD4 testing has the potential to address some of the challenges of centralized CD4 testing and delays in delivery of timely testing and ART initiation. We conducted a systematic review and meta-analysis to identify the extent to which POC improves linkages to HIV care and timeliness of ART initiation.

Methods: We searched two databases and four conference sites between January 2005 and April 2015 for studies reporting test turnaround times, proportion of results returned, and retention associated with the use of point-of-care CD4. Random effects models were used to estimate pooled risk ratios, pooled proportions, and 95% confidence intervals.

Results: We identified 30 eligible studies, most of which were completed in Africa. Test turnaround times were reduced with the use of POC CD4. The time from HIV diagnosis to CD4 test was reduced from 10.5 days with conventional laboratory-based testing to 0.1 days with POC CD4 testing. Retention along several steps of the treatment initiation cascade was significantly higher with POC CD4 testing, notably from HIV testing to CD4 testing, receipt of results, and pre-CD4 test retention (all p<0.001). Furthermore, retention between CD4 testing and ART initiation increased with POC CD4 testing compared to conventional laboratory-based testing (p = 0.01). We also carried out a non-systematic review of the literature observing that POC CD4 increased the projected life expectancy, was cost-effective, and acceptable.

Conclusions: POC CD4 technologies reduce the time and increase patient retention along the testing and treatment cascade compared to conventional laboratory-based testing. POC CD4 is, therefore, a useful tool to perform CD4 testing and expedite result delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0155256PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4866695PMC
July 2017

Reducing mortality in HIV-infected infants and achieving the 90-90-90 target through innovative diagnosis approaches.

J Int AIDS Soc 2015 2;18(Suppl 6):20299. Epub 2015 Dec 2.

World Health Organization, Geneva, Switzerland.

Introduction: Despite significant gains in access to early infant diagnosis (EID) over the past decade, most HIV-exposed infants still do not get tested for HIV in the first two months of life. For those who are tested, the long turnaround time between when the sample is drawn and when the results are returned leads to a high rate of loss to follow-up, which in turn means that few infected infants start antiretroviral treatment. Consequently, there continues to be high mortality from perinatally acquired HIV, and the ambitious goals of 90% of infected children identified, 90% of identified children treated and 90% of treated children with sustained virologic suppression by 2020 seem far beyond our reach. The objective of this commentary is to review recent advances in the field of HIV diagnosis in infants and describe how these advances may overcome long-standing barriers to access to testing and treatment.

Discussion: Several innovative approaches to EID have recently been described. These include point-of-care testing, use of SMS printers to connect the central laboratory and the health facility through a mobile phone network, expanding paediatric testing to other entry points where children access the health system and testing HIV-exposed infants at birth as a rapid way to identify in utero infection. Each of these interventions is discussed here, together with the opportunities and challenges associated with scale-up. Point-of-care testing has the potential to provide immediate results but is less cost-effective in settings where test volumes are low. Virological testing at birth has been piloted in some countries to identify those infants who need urgent treatment, but a negative test at birth does not obviate the need for additional testing at six weeks. Routine testing of infants in child health settings is a useful strategy to identify exposed and infected children whose mothers were not enrolled in programmes for the prevention of mother-to-child transmission. Facility-based SMS printers speed up the return of laboratory results and may be of value for other testing services apart from HIV infant diagnosis.

Conclusions: New tools and strategies for HIV infant diagnosis could have a significant positive impact on the identification and retention of HIV-infected infants. In order to be most effective, national programmes should carefully consider which ideas to implement and how best to integrate novel strategies into existing systems. There is no single solution that will work everywhere. Rather, a number of approaches need to be considered and should be linked in order to achieve the greatest impact on the continuum of care from testing to treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4670838PMC
http://dx.doi.org/10.7448/IAS.18.7.20299DOI Listing
August 2016

CD4 changes among virologically suppressed patients on antiretroviral therapy: a systematic review and meta-analysis.

J Int AIDS Soc 2015 7;18:20061. Epub 2015 Aug 7.

Department of Pharmacology and Therapeutics, Liverpool University, Liverpool, United Kingdom.

Introduction: The effectiveness of antiretroviral therapy (ART) is assessed by measuring CD4 cell counts and viral load. Recent studies have questioned the added value of routine CD4 cell count measures in patients who are virologically suppressed.

Methods: We systematically searched three databases and two conference sites up to 31 October 2014 for studies reporting CD4 changes among patients who were on ART and virologically suppressed. No geographic, language or age restrictions were applied.

Results And Discussion: We identified 12 published and 1 unpublished study reporting CD4 changes among 20,297 virologically suppressed patients. The pooled proportion of patients who experienced an unexplained, confirmed CD4 decline was 0.4% (95% CI 0.2-0.6%). Results were not influenced by duration of follow-up, age, study design or region of economic development. No studies described clinical adverse events among virologically suppressed patients who experienced CD4 declines.

Conclusions: The findings of this review support reducing or stopping routine CD4 monitoring for patients who are immunologically stable on ART in settings where routine viral load monitoring is provided.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530137PMC
http://dx.doi.org/10.7448/IAS.18.1.20061DOI Listing
March 2016

Multisite evaluation of point of care CD4 testing in Papua New Guinea.

PLoS One 2014 26;9(11):e112173. Epub 2014 Nov 26.

Clinton Health Access Initiative, Goroka, Papua New Guinea.

Laboratory-based CD4 monitoring of HIV patients presents challenges in resource limited settings (RLS) including frequent machine breakdown, poor engineering support and limited cold chain and specimen transport logistics. This study assessed the performance of two CD4 tests designed for use in RLS; the Dynal assay and the Alere PIMA test (PIMA). Accuracy of Dynal and PIMA using venous blood was assessed in a centralised laboratory by comparison to BD FACSCount (BD FACS). Dynal had a mean bias of -50.35 cells/µl (r(2) = 0.973, p<0.0001, n = 101) and PIMA -22.43 cells/µl (r(2)= 0.964, p<0.0001, n = 139) compared to BD FACS. Similar results were observed for PIMA operated by clinicians in one urban (n = 117) and two rural clinics (n = 98). Using internal control beads, PIMA precision was 10.34% CV (low bead mean 214.24 cells/µl) and 8.29% (high bead mean 920.73 cells/µl) and similar %CV results were observed external quality assurance (EQA) and replicate patient samples. Dynal did not perform using EQA and no internal controls are supplied by the manufacturer, however duplicate testing of samples resulted in r(2) = 0.961, p<0.0001, mean bias =  -1.44 cells/µl. Using the cut-off of 350 cells/µl compared to BD FACS, PIMA had a sensitivity of 88.85% and specificity of 98.71% and Dynal 88.61% and 100%. A total of 0.44% (2/452) of patient samples were misclassified as "no treat" and 7.30% (33/452) "treat" using PIMA whereas with Dynal 8.91% (9/101) as "treat" and 0% as "no treat". In our setting PIMA was found to be accurate, precise and user-friendly in both laboratory and clinic settings. Dynal performed well in initial centralized laboratory evaluation, however lacks requisite quality control measures, and was technically more difficult to use, making it less suitable for use at lower tiered laboratories.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0112173PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4245096PMC
July 2015

A long, naturally presented immunodominant epitope from NY-ESO-1 tumor antigen: implications for cancer vaccine design.

Cancer Res 2009 Feb 27;69(3):1046-54. Epub 2009 Jan 27.

Ludwig Institute for Cancer Research, Melbourne Centre for Clinical Sciences, Austin Health, Heidelberg, Victoria, Australia.

The tumor antigen NY-ESO-1 is a promising cancer vaccine target. We describe here a novel HLA-B7-restricted NY-ESO-1 epitope, encompassing amino acids 60-72 (APRGPHGGAASGL), which is naturally presented by melanoma cells. The tumor epitope bound to HLA-B7 by bulging outward from the peptide-binding cleft. This bulged epitope was not an impediment to T-cell recognition, however, because four of six HLA-B7(+) melanoma patients vaccinated with NY-ESO-1 ISCOMATRIX vaccine generated a potent T-cell response to this determinant. Moreover, the response to this epitope was immunodominant in three of these patients and, unlike the T-cell responses to bulged HLA class I viral epitopes, the responding T cells possessed a remarkably broad TCR repertoire. Interestingly, HLA-B7(+) melanoma patients who did not receive the NY-ESO-1 ISCOMATRIX vaccine rarely generated a spontaneous T-cell response to this cryptic epitope, suggesting a lack of priming of such T cells in the natural anti-NY-ESO-1 response, which may be corrected by vaccination. Together, our results reveal several surprising aspects of antitumor immunity and have implications for cancer vaccine design.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/0008-5472.CAN-08-2926DOI Listing
February 2009

Induction of tumor-specific T cell memory by NK cell-mediated tumor rejection.

Nat Immunol 2002 Jan 17;3(1):83-90. Epub 2001 Dec 17.

Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, St. Andrews Place, East Melbourne, Victoria, Australia.

Natural killer (NK) cells may modulate the development of adaptive immune responses, but until now there has been little evidence to support this hypothesis. We investigated the primary and secondary immunity elicited by various tumor cell lines that express CD70 and interact with CD70 ligand (CD27), which is constitutively expressed on NK cells. CD70 expression enhanced primary tumor rejection in vivo as well as T cell immunity against secondary tumor challenge. Primary rejection of major histocompatibility complex (MHC) class I-deficient RMA-S.CD70 tumor cells was mediated by NK cells and perforin- and interferon-gamma-dependent mechanisms. This NK cell-mediated process also efficiently evoked the subsequent development of tumor-specific cytotoxic and T helper type 1 responses to the parental, MHC class I-sufficient, RMA tumor cells. Thus CD27-CD70 interactions provide a key link between innate NK cell responses and adaptive T cell immunity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ni746DOI Listing
January 2002
-->