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1.
J Med Internet Res ; 19(12): e408, 2017 12 22.
Article in English | MEDLINE | ID: mdl-29273572

ABSTRACT

BACKGROUND: Social networking sites, in particular Facebook, are not only predominant in students' social life but are to varying degrees interwoven with the medical curriculum. Particularly, Facebook groups have been identified for their potential in higher education. However, there is a paucity of data on user types, content, and dynamics of study-related Facebook groups. OBJECTIVE: The aim of this study was to identify the role of study-related Facebook group use, characterize medical students that use or avoid using Facebook groups (demographics, participation pattern, and motivation), and analyze student posting behavior, covered topics, dynamics, and limitations in Facebook groups with regards to educational usage. METHODS: Using a multi-method approach (interviews, focus groups, and qualitative and quantitative analysis of Facebook posts), we analyzed two representative Facebook groups of medical preclinical semesters at Ludwig-Maximilians-University (LMU) Munich. Facebook primary posts and replies over one semester were extracted and evaluated by using thematic content analysis. We developed and applied a coding scheme for studying the frequency and distribution of these posts. Additionally, we interviewed students with various degrees of involvement in the groups, as well as "new minorities," students not registered on Facebook. RESULTS: Facebook groups seem to have evolved as the main tool for medical students at LMU to complement the curriculum and to discuss study-related content. These Facebook groups are self-organizing and quickly adapt to organizational or subject-related challenges posed by the curriculum. A wide range of topics is covered, with a dominance of organization-related posts (58.35% [6916/11,853] of overall posts). By measuring reply rates and comments per category, we were able to identify learning tips and strategies, material sharing, and course content discussions as the most relevant categories. Rates of adequate replies in these categories ranged between 78% (11/14) and 100% (13/13), and the number of comments per post ranged from 8.4 to 13.7 compared with the average overall reply rate of 68.69% (1167/1699) and 3.9 comments per post. User typology revealed social media drivers (>30 posts per semester) as engines of group function, frequent users (11-30 posts), and a majority of average users acting rather as consumers or lurkers (1-10 posts). CONCLUSIONS: For the moment, the medical faculty has no active involvement in these groups and therefore no influence on accuracy of information, professionalism, and ethical issues. Nevertheless, faculty could in the future benefit by extracting relevant information, identifying common problems, and understanding semester-related dynamics.


Subject(s)
Education, Medical/methods , Social Media/instrumentation , Female , Humans , Learning , Male , Social Networking
2.
GMS J Med Educ ; 34(3): Doc30, 2017.
Article in English | MEDLINE | ID: mdl-28890921

ABSTRACT

Introduction: One of the most important extracurricular aspects of medical studies in Germany is a research thesis completed by most students. This research project often times conveys relevant competencies for the physician's role as scientist. Nevertheless, the choice of the right project remains a challenge. Reasons for this are among others, missing structures for a comprehensive overview of research groups and their respective projects. Description of the project: We developed the online platform Doktabörse as an online marketplace for doctoral research projects. The platform enables authorized researchers to create working groups and upload, deactivate and change research projects within their institute. For interested students, a front end with integrated search function displays these projects in a structured and well-arranged way. In parallel, the Doktabörse provides for a comprehensive overview of research at the medical faculty. We evaluated Researchers' and students' use of the platform. Results: 96,6% of students participating in the evaluation (n=400) were in favor of a centralized research platform at the medical faculty. The platform grew at a steady pace and included 120 research groups in June 2016. The students appreciated the structure and design of the Doktabörse. Two thirds of all uploaded projects matched successfully with doctoral students via the platform and over 94% of researchers stated that they did not need technical assistance with uploading projects and handling the platform. Discussion: The Doktabörse represents an innovative and well accepted platform for doctoral research projects. The platform is perceived positively by researchers and students alike. However, students criticized limited extent and timeliness of offered projects. In addition, the platform serves as databank of research at the medical faculty of the LMU Munich. The future potential of this platform is to provide for an integrated management solution of doctoral thesis projects, possibly beyond the medical field and faculty.


Subject(s)
Academic Dissertations as Topic , Biomedical Research , Databases as Topic , Faculty, Medical , Hospitals, University , Internet , Software Design , Clinical Competence , Curriculum , Germany , Humans , Physician's Role
3.
GMS J Med Educ ; 33(3): Doc41, 2016.
Article in English | MEDLINE | ID: mdl-27275506

ABSTRACT

INTRODUCTION: During their formal studies medical students acquire extensive medical expertise. However, the medical profession demands additional competencies, such as those involved in efficient resource allocation, business administration, development, organization, and process management in the healthcare system. At present students are not sufficiently prepared for the physician's role as manager. In response, we designed the seminar course, MeCuM-SiGma, to impart basic knowledge about healthcare policy and management to students of medicine. This project report describes our teaching strategies and the initial evaluation of this educational project. PROJECT DESCRIPTION: In this semester-long, seminar course introduced in 2010, medical students gather experience with the competencies mentioned above as well as learn basic management skills. The course is offered each winter semester, and students sign up to attend voluntarily; course coordination and organization is done on a voluntary basis by physicians and employees of the Mentoring Office (MeCuM-Mentor) at the Medical School of the Ludwig Maximilian University (LMU) in Munich, Germany. The course is open to all students enrolled at the two medical schools in Munich. During the first part of this elective, students learn about the basic principles of the German political and healthcare systems in case-based, problem-based tutorials led by trained tutors and in lectures held by experts. In the second part of the course students take on the roles of the University Hospital's executive board of directors and supervisory board to work on an existing hospital project as a group within the scope of a simulation. This phase of the course is accompanied by workshops conducted in cooperation with university-based and off-campus partners that address the procedural learning objectives (teamwork, project management, negotiation strategies, etc.). A suitable, authentic issue currently facing the hospital is selected in advance by the course organizers in coordination with the hospital's executive board. Students then work on this issue in the third and final phase of the course under the supervision of tutors and with assistance from hospital employees. At the end of the course the students formally present the results of their work to the hospital's executive and supervisory boards. RESULTS: The course undergoes written student evaluation, a round of oral feedback, evaluation of the final projects, and feedback from the hospital's executive and supervisory boards. All attendees to date have reported a substantial gain in general knowledge and increased knowledge about the healthcare system, and rate the relevance of the course as being high. The majority felt the content was important for their future practice of medicine. Overall, students evaluated the course very positively [overall rating on a six-point grading scale (1=excellent; 6=unsatisfactory): 1.28 (mean)±0.45 (standard deviation)]. DISCUSSION: The importance of the physician's role as manager in medical organizations and as a guiding force in the healthcare system is neglected in medical degree programs. Our seminar course attempts to address this shortcoming, is the object of great interest and receives positive evaluations from seminar participants, our cooperative partners and the executive and supervisory boards of the University Hospital in Munich.


Subject(s)
Curriculum , Delivery of Health Care , Students, Medical , Germany , Humans , Schools, Medical
4.
Med Teach ; 38(9): 921-9, 2016 Sep.
Article in English | MEDLINE | ID: mdl-26822503

ABSTRACT

BACKGROUND: Spontaneous formation of mentoring relationships can be seen as the gold standard in mentoring. Unfortunately, it happens very infrequently. The purpose of structured mentoring programmes is to facilitate the formation of mentoring relationships. This remains a challenging task, especially for large institutions. AIMS: We set out to investigate and compare three methods of matchmaking in the setting of our structured mentoring programme. In a prospective, randomised trial we compared personal matching (PM) by an experienced expert to two different electronic data processing (EDP)-supported matching procedures: "online algorithm" (OA) versus "online search" (OS). METHODS: PM was performed after structured interviews of prospective protégés by one founder of our mentoring programme. The OA provides students with a choice of 10 potential mentors based on comparison of online profiles. OS lets students filter and search through all available mentor profiles. One hundred and ninty medical students were randomised into the three groups. One year later, we evaluated the endpoints 1. "establishment of a mentoring relationship" and 2. "satisfaction with the mentoring relationship". Satisfaction with the mentoring relationship was assessed using Munich-Evaluation-of-Mentoring-Questionnaire (MEMeQ). RESULTS: One hundred sixty-five out of the 190 study participants found a mentor. With regards to endpoint one we found an advantage of PM compared to both EDP-supported matching procedures. There was no significant difference between OA and OS. Concerning endpoint two the differences between the investigated matching procedures were not significant. CONCLUSION: PM is superior as to the number of mentoring relationships formed per participating student compared to EDP-supported methods. In our data, there was no significant difference in the level of satisfaction. Considering the high investments associated with PM of mentors and protégés, EDP-supported matching procedures seem a viable compromise between effectiveness and efficiency especially for large-scale structured mentoring programmes in medical education.


Subject(s)
Education, Medical , Mentoring/organization & administration , Students, Medical , Adult , Education, Medical/methods , Female , Humans , Male , Prospective Studies , Surveys and Questionnaires , Young Adult
5.
BMC Med Educ ; 15: 201, 2015 Nov 09.
Article in English | MEDLINE | ID: mdl-26553241

ABSTRACT

BACKGROUND: Despite the widespread recognition of the importance of mentoring in medical education, valid and reliable instruments for evaluating the relationship of mentors and protégés are lacking. The aim of this study was to develop a feasible instrument to measure the satisfaction with mentoring relationships. METHODS: Based on two existing questionnaires, the authors developed an instrument to evaluate the weighted satisfaction of mentoring relationships, emphasizing the protégés' individual expectations and needs. Protégés first define individual areas of interest in their mentoring relationship, then assign relative levels of personal importance to them and finally rate their individual level of satisfaction with their mentors' support in each area of interest. In order to evaluate psychometric properties as well as acceptance and feasibility the investigators conducted a multi-method-study. RESULTS: 134 protégés were included in the study. The instrument was neither perceived as distressing nor time-consuming. The two scores of the questionnaire correlated closely with the overall satisfaction regarding mentoring relationships (OSM, Rho: 0.66, p <.001 and Rho: 0.53, p < .001). CONCLUSIONS: The authors propose MEMeQ as a reliable, valid and flexible instrument for measuring the weighted satisfaction of protégés with their individual mentoring relationship in medical education. Further research is needed to evaluate the generalizability of MEMeQ across other institutions and mentoring programs to add to its validity.


Subject(s)
Personal Satisfaction , Surveys and Questionnaires , Adult , Clinical Competence , Education, Medical/methods , Female , Germany , Humans , Interprofessional Relations , Male , Mentors , Reproducibility of Results
6.
GMS Z Med Ausbild ; 32(3): Doc29, 2015.
Article in English | MEDLINE | ID: mdl-26413167

ABSTRACT

INTRODUCTION: The importance of research, as promoted by the CanMEDS framework, is widely acknowledged. Many medical students in Germany work on a research project as part of their doctoral thesis whilst still going to medical school. However, a significant amount of projects are abandoned unfinished, which leads to substantial wastage of resources. One reason for this is an information deficit concerning undergraduate research projects. PROJECT DESCRIPTION: To counteract this, we introduced an annual event at LMU Munich called DoktaMed with more than 600 visitors each year. It combines medical convention and research fair including keynote lectures, workshops and poster sessions as well as an exhibition of research groups and institutes. DoktaMed is a peer-to-peer event organized by a team of 40 students. RESULTS: A needs analysis before its implementation underlined the information deficit as a possible cause for the high rate of abandoned projects. In the annual evaluation, visitors of DoktaMed rate the event with an average grade of 2.1 on a six-level Likert scale (n=558, SD=1.06, with "1=very good", "6=poor"). They stated to now feel better informed about the topic and regarded visiting DoktaMed as a worthwhile investment of time. DISCUSSION: Students are generally satisfied with the event and feel better informed after visiting DoktaMed. However, many students never visit DoktaMed for various reasons. A possible improvement would be to present a greater number of clinical studies in addition to the laboratory work that DoktaMed focuses on now. CONCLUSION: Evaluation after six years of DoktaMed is very promising. Visitors seem to be better informed. Nevertheless there is space for improvement in order to get more students and more faculty members involved. More studies are needed to assess long-term effects.


Subject(s)
Academic Dissertations as Topic , Biomedical Research/education , Congresses as Topic , Education, Medical, Undergraduate , Attitude of Health Personnel , Curriculum , Germany , Humans , Students, Medical
7.
GMS Z Med Ausbild ; 32(1): Doc5, 2015.
Article in English | MEDLINE | ID: mdl-25699108

ABSTRACT

In this paper we present our 5-year-experience with a large-scale mentoring program for undergraduate medical students at the Ludwig Maximilians-Universität Munich (LMU). We implemented a two-tiered program with a peer-mentoring concept for preclinical students and a 1:1-mentoring concept for clinical students aided by a fully automated online-based matching algorithm. Approximately 20-30% of each student cohort participates in our voluntary mentoring program. Defining ideal program evaluation strategies, recruiting mentors from beyond the academic environment and accounting for the mentoring network reality remain challenging. We conclude that a two-tiered program is well accepted by students and faculty. In addition the online-based matching seems to be effective for large-scale mentoring programs.


Subject(s)
Education, Medical, Undergraduate/organization & administration , Mentors/education , Peer Group , Career Choice , Clinical Competence , Curriculum , Germany , Physician's Role , Program Evaluation
8.
JMIR Med Educ ; 1(2): e12, 2015 Oct 27.
Article in English | MEDLINE | ID: mdl-27731859

ABSTRACT

BACKGROUND: Peer mentoring is a powerful pedagogical approach for supporting undergraduate medical students in their learning environment. However, it remains unclear what exactly peer mentoring is and whether and how undergraduate medical students use social media for peer-mentoring activities. OBJECTIVE: We aimed at describing and exploring the Facebook use of undergraduate medical students during their first 2 years at a German medical school. The data should help medical educators to effectively integrate social media in formal mentoring programs for medical students. METHODS: We developed a coding scheme for peer mentoring and conducted a mixed-methods study in order to explore Facebook groups of undergraduate medical students from a peer-mentoring perspective. RESULTS: All major peer-mentoring categories were identified in Facebook groups of medical students. The relevance of these Facebook groups was confirmed through triangulation with focus groups and descriptive statistics. Medical students made extensive use of Facebook and wrote a total of 11,853 posts and comments in the respective Facebook groups (n=2362 total group members). Posting peaks were identified at the beginning of semesters and before exam periods, reflecting the formal curriculum milestones. CONCLUSIONS: Peer mentoring is present in Facebook groups formed by undergraduate medical students who extensively use these groups to seek advice from peers on study-related issues and, in particular, exam preparation. These groups also seem to be effective in supporting responsive and large-scale peer-mentoring structures; formal mentoring programs might benefit from integrating social media into their activity portfolio.

9.
GMS Z Med Ausbild ; 31(2): Doc17, 2014.
Article in English | MEDLINE | ID: mdl-24872852

ABSTRACT

OBJECTIVE: The selection of a future medical specialty is a challenge all medical students face during the course of their studies. Students can choose from more than sixty specialties after graduation. There is usually no structured career counselling program available at German medical faculties. So far only little data on acceptance, formats and effects of different career counselling programs are available. The aim of this study is to describe an innovative format of career counselling for medical students including its evaluation of acceptance and its possible influence on medical specialty preferences. METHODS: The need for career counselling became evident after the analysis of mentor-mentee conversations held within the mentoring program of our medical faculty, an online-based survey, an ad-hoc focus group and a pilot event. Panel discussions as an interactive format of presenting related medical specialties were developed and hence held four times under the name "FacharztDuell". Students evaluated all events separately with a questionnaire and changes in medical specialty choice preferences were documented using an Audience-Response-System (ARS). The FacharztDuell is organized regularly and supported by faculty teaching funds. RESULTS: Among the student body FacharztDuell was well accepted (an average of 300 participants/event) and rated (average grade of 1.8 (SD= 0.7, 1=very good, 6=unsatisfactory, n=424). On average, 77.8% of the participating students considered the FacharztDuell to be a decision support for their future selection of a specialty. Up to 12% of the students changed their medical specialty choice preference throughout the event. CONCLUSION: FacharztDuell was well accepted by medical students of all semesters and seems to be supportive for their selection of a future medical specialty. However, longitudinal studies are necessary to better understand the decision making process of medical students along their career path. The FacharztDuell is easily transferrable to other faculties with respect to organization, staff and technical resources.


Subject(s)
Education, Medical, Graduate , Medicine , Students, Medical/psychology , Vocational Guidance , Career Choice , Decision Support Techniques , Germany , Humans , Surveys and Questionnaires
12.
Med Educ Online ; 17(1): 17242, 2012 09 13.
Article in English | MEDLINE | ID: mdl-22989620

ABSTRACT

BACKGROUND: Little is known about the characteristics of mentoring relationships formed between faculty and medical students. Individual mentoring relationships of clinical medical students at Munich Medical School were characterized quantitatively and qualitatively. METHODS: All students signing up for the mentoring program responded to a questionnaire on their expectations (n = 534). Mentees were asked to give feedback after each of their one-on-one meetings (n = 203). A detailed analysis of the overall mentoring process and its characteristics was performed. For qualitative text analysis, free-text items were analyzed and categorized by two investigators. Quantitative analysis was performed using descriptive statistics and Wilcoxon-test to assess differences in grades between students with and without mentors. RESULTS: High-performing students were significantly more likely to participate in the mentoring program (p<0.001). Topics primarily discussed include the mentee's personal goals (65.5%), career planning (59.6%), and experiences abroad (57.6%). Mentees mostly perceived their mentors as counselors (88.9%), providers of ideas (85.0%), and role models (73.3%). Mentees emphasized the positive impact of the mentoring relationship on career planning (77.2%) and research (75.0%). CONCLUSIONS: Medical students with strong academic performance as defined by their grades are more likely to participate in formal mentoring programs. Mentoring relationships between faculty and medical students are perceived as a mutually satisfying and effective instrument for key issues in medical students' professional development. PRACTICAL IMPLICATIONS: Mentoring relationships are a highly effective means of enhancing the bidirectional flow of information between faculty and medical students. A mentoring program can thus establish a feedback loop enabling the educational institution to swiftly identify and address issues of medical students.


Subject(s)
Faculty, Medical/statistics & numerical data , Interpersonal Relations , Mentors/psychology , Students, Medical/psychology , Education, Medical, Graduate , Educational Measurement , Female , Humans , Male , Mentors/statistics & numerical data , Professional Role , Sex Factors , Students, Medical/statistics & numerical data
13.
BMC Med Educ ; 11: 68, 2011 Sep 24.
Article in English | MEDLINE | ID: mdl-21943281

ABSTRACT

BACKGROUND: Despite increasing recognition that mentoring is essential early in medical careers, little is known about the prevalence of mentoring programs for medical students. We conducted this study to survey all medical schools in Germany regarding the prevalence of mentoring programs for medical students as well as the characteristics, goals and effectiveness of these programs. METHODS: A definition of mentoring was established and program inclusion criteria were determined based on a review of the literature. The literature defined mentoring as a steady, long-lasting relationship designed to promote the mentee's overall development. We developed a questionnaire to assess key characteristics of mentoring programs: the advocated mentoring model, the number of participating mentees and mentors, funding and staff, and characteristics of mentees and mentors (e.g., level of training). In addition, the survey characterized the mentee-mentor relationship regarding the frequency of meetings, forms of communication, incentives for mentors, the mode of matching mentors and mentees, and results of program evaluations. Furthermore, participants were asked to characterize the aims of their programs. The questionnaire consisted of 34 questions total, in multiple-choice (17), numeric (7) and free-text (10) format. This questionnaire was sent to deans and medical education faculty in Germany between June and September 2009. For numeric answers, mean, median, and standard deviation were determined. For free-text items, responses were coded into categories using qualitative free text analysis. RESULTS: We received responses from all 36 medical schools in Germany. We found that 20 out of 36 medical schools in Germany offer 22 active mentoring programs with a median of 125 and a total of 5,843 medical students (6.9 - 7.4% of all German medical students) enrolled as mentees at the time of the survey. 14 out of 22 programs (63%) have been established within the last 2 years. Six programs (27%) offer mentoring in a one-on-one setting. 18 programs (82%) feature faculty physicians as mentors. Nine programs (41%) involve students as mentors in a peer-mentoring setting. The most commonly reported goals of the mentoring programs include: establishing the mentee's professional network (13 programs, 59%), enhancement of academic performance (11 programs, 50%) and counseling students in difficulties (10 programs, 45%). CONCLUSIONS: Despite a clear upsurge of mentoring programs for German medical students over recent years, the overall availability of mentoring is still limited. The mentoring models and goals of the existing programs vary considerably. Outcome data from controlled studies are needed to compare the efficiency and effectiveness of different forms of mentoring for medical students.


Subject(s)
Education, Medical/methods , Mentors/statistics & numerical data , Schools, Medical/statistics & numerical data , Students, Medical/statistics & numerical data , Cross-Sectional Studies , Germany , Humans , Interpersonal Relations , Surveys and Questionnaires
14.
GMS Z Med Ausbild ; 28(2): Doc26, 2011.
Article in English | MEDLINE | ID: mdl-21818236

ABSTRACT

PURPOSE: Mentoring plays an important role in students' performance and career. The authors of this study assessed the need for mentoring among medical students and established a novel large-scale mentoring program at Ludwig-Maximilians-University (LMU) Munich School of Medicine. METHODS: Needs assessment was conducted using a survey distributed to all students at the medical school (n=578 of 4,109 students, return rate 14.1%). In addition, the authors held focus groups with selected medical students (n=24) and faculty physicians (n=22). All students signing up for the individual mentoring completed a survey addressing their expectations (n=534). RESULTS: Needs assessment revealed that 83% of medical students expressed overall satisfaction with the teaching at LMU. In contrast, only 36.5% were satisfied with how the faculty supports their individual professional development and 86% of students voiced a desire for more personal and professional support. When asked to define the role of a mentor, 55.6% "very much" wanted their mentors to act as counselors, arrange contacts for them (36.4%), and provide ideas for professional development (28.1%). Topics that future mentees "very much" wished to discuss included research (56.6%), final year electives (55.8%) and experiences abroad (45.5%). CONCLUSIONS: Based on the strong desire for mentoring among medical students, the authors developed a novel two-tiered system that introduces one-to-one mentoring for students in their clinical years and offers society-based peer mentoring for pre-clinical students. One year after launching the program, more than 300 clinical students had experienced one-to-one mentoring and 1,503 students and physicians were involved in peer mentoring societies.

15.
J Immunol ; 185(4): 2580-8, 2010 Aug 15.
Article in English | MEDLINE | ID: mdl-20644173

ABSTRACT

In stomach cancer, there is a need for new therapeutic strategies, in particular for the treatment of unresectable tumors and micrometastases. We investigated the efficacy of immunotherapy in an autochthonous model of gastric cancer, the CEA424-SV40 T Ag (TAg) transgenic mice. Treatment efficacy against both the autochthonous tumors and s.c. tumors induced by the derived cell line mGC3 were assessed. In wild-type mice, a dendritic cell vaccine loaded with irradiated tumor cells combined with CpG oligonucleotides induced efficient cytotoxic T cell and memory responses against mGC3 s.c. tumors. In contrast, neither s.c. nor autochthonous tumors responded to vaccination in CEA424-SV40 TAg mice, indicating tolerance to the SV40 TAg. To examine whether tumors in these mice were principally accessible to immunotherapy, splenocytes from immune wild-type mice were adoptively transferred into CEA424-SV40 TAg transgenic mice. Treated mice showed complete regression of the s.c. tumors associated with intratumoral infiltrates of CD8 and CD4 T cells. In contrast, the autochthonous gastric tumors in the same mice were poorly infiltrated and did not regress. Thus, even in the presence of an active anti-tumoral T cell response, autochthonous gastric tumors do not respond to immunotherapy. This is the first comparison of the efficacy of adoptive T cell transfer between transplanted s.c. tumors and autochthonous tumors in the same animals. Our results suggest that in gastric cancer patients, even a strong anti-tumor T cell response will not efficiently penetrate the tumor in the absence of additional therapeutic strategies targeting the tumor microenvironment.


Subject(s)
Disease Models, Animal , Immunotherapy, Adoptive/methods , Stomach Neoplasms/therapy , T-Lymphocytes/transplantation , Animals , Antigens, Polyomavirus Transforming/genetics , Cancer Vaccines/adverse effects , Cancer Vaccines/immunology , Carcinoembryonic Antigen/genetics , Cell Line, Tumor , Combined Modality Therapy , CpG Islands/genetics , Dendritic Cells/immunology , Female , Mice , Mice, Inbred C57BL , Mice, Transgenic , Oligonucleotides/administration & dosage , Oligonucleotides/genetics , Promoter Regions, Genetic/genetics , Recombinant Fusion Proteins/genetics , Spleen/cytology , Spleen/immunology , Stomach Neoplasms/genetics , Stomach Neoplasms/immunology , Survival Analysis , T-Lymphocytes/immunology , Vaccination
17.
J Immunol ; 181(5): 2990-8, 2008 Sep 01.
Article in English | MEDLINE | ID: mdl-18713969

ABSTRACT

Viral nucleic acids are recognized by specific pattern-recognition receptors of the Toll-like and RIG-I-like receptor families. Synthetic DNA and RNA oligonucleotides can activate the immune system through these receptors and potentiate Ab and CD8 cytotoxic responses to Ags. Systemic application of immunostimulatory oligonucleotides however also results in a generalized, non-Ag-specific stimulation of the immune system. In this study, we have dissociated the induction of an Ag-specific response from the systemic immune activation generally associated with immunostimulatory oligonucleotides. Delivery of CpG oligodeoxynucleotides that bind TLR9 by cationized gelatin-based nanoparticles potentiates the in vivo generation of an Ag-specific cytotoxic T cell and Ab response. Furthermore, immunization with CpG-loaded nanoparticles induces a protective antitumoral response in a murine model of melanoma. The systemic release of proinflammatory cytokines and widespread immunostimulation associated with free CpG is however completely abolished. In addition, we show that gelatin nanoparticle formulation prevents the destruction of lymphoid follicles mediated by CpG. Nanoparticle-delivered CpG, in contrast to free CpG, are selectively targeted to APCs in the lymph nodes where they mediate local immune stimulation. We describe a novel strategy to target immunostimulatory oligonucleotides to the initiation site of the immune response while at the same time protecting from an indiscriminate and generalized activation of the immune system.


Subject(s)
Immunity/drug effects , Lymph Nodes/metabolism , Nanoparticles/administration & dosage , Neoplasms/therapy , Oligodeoxyribonucleotides/administration & dosage , Animals , Drug Delivery Systems/methods , Female , Gelatin , Immunotherapy/methods , Lymph Nodes/immunology , Mice , Neoplasms/immunology , Oligodeoxyribonucleotides/pharmacokinetics , T-Lymphocytes, Cytotoxic/immunology , Th1 Cells/immunology , Toll-Like Receptor 9/metabolism
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