Podcasts about ptld

Born with congenital heart disease, Kameryn Raspberry never let it hold her back. From her earliest procedures as an infant to her transplant at age 12, Kameryn's spirit, and her desire for a normal childhood, were supported by her parents' love. Hear Kameryn's story, including the pivotal moment on April 4, 2018, when doctors discussed her slim chances of receiving a donor heart. Against all odds, a timely call changed everything. Receiving her new heart, Kameryn embraced life anew, rediscovering the joys of childhood activities, and simply walking and eating with joy. Yet, Kameryn's journey continued post-transplant, marked by battles with lymphoproliferative disorder (PTLD), enduring cancer three times and becoming diabetic due to medication side effects. Through it all, Kameryn's spirit shines, sharing her story of courage, hope and the transformative power of her transplant.

The JHLT Digital Media Editors explore two manuscripts from the August issue of The Journal of Heart and Lung Transplantation—the first on immunosuppression in pediatric heart transplantation, and the second TA-NRP in DCD lung transplantation. Digital Media Editor Van-Khue Ton, MD, heart failure and transplant cardiologist at Massachusetts General Hospital, hosts this episode.   First, hear from senior author Steven C. Greenway, MSc, MD, on his team's study “Single-drug immunosuppression is associated with noninferior medium-term survival in pediatric heart transplant recipients.” Dr. Greenway shares his journey from enzyme biochemistry in mollusks, snails, and frogs to pediatric cardiology, then outlines the results of the paper.   The study queried the Pediatric Heart Transplant Society's registry to determine the efficacy and safety of monotherapy immunosuppression. The results showed better graft survival and less coronary allograft vasculopathy in the monotherapy group, even after adjusted for age at transplant, sex, neonatal transplant, infection, PTLD, and etiology of cardiomyopathy. Dr. Greenway and the digital media editors discuss the burning questions that obviously arise from the study's findings, the limitations of the paper, and what follow-up studies might start generating the answers that might eventually change clinical practice.   Next, the editors welcome first author Jad Malas, MD, to discuss the paper “The impact of thoracoabdominal normothermic regional perfusion on early outcomes in donation after circulatory death lung transplantation.” This study utilized the United Network of Organ Sharing (UNOS) database to identify DCD donors whose heart was procured in order to evaluate lung utilization rates and early post-lung transplant outcomes. Lung utilization was similar between the groups—14.9% for the NRP group and 13.8% for direct procurement. Post-lung transplant rates of ECMO and mechanical ventilation at 72 hours were not statistically different, and 6-month survival was equivalent.   Dr. Malas and the Digital Media Editors discuss the study's findings and implications, including exploring the background of NRP's relationship to lung allografts, differences in assessment or procurement techniques, and what might be needed to further evaluate this procurement technique for lung allografts.   Follow along at www.jhltonline.org/current, or, if you're an ISHLT member, log in at ishlt.org/journal-of-heart-lung-transplantation.  Don't already get the Journal and want to read along? Join the International Society of Heart and Lung Transplantation at www.ishlt.org for a free subscription, or subscribe today at www.jhltonline.org.   This episode of JHLT: The Podcast, but not the studies within, is sponsored by Natera.

O uso de um imunossupressor após a realização de um transplante de pulmão fez com que um dos pacientes que a Abrale recentemente entrou em contato desenvolvesse linfoma.    O surgimento de um linfoma pós-transplante de órgão sólido é raro mas pode acontecer. Essa complicação é conhecida como “PTLD” (que significa, em português, doença linfoproliferativa pós-transplante).     Algumas condições podem favorecer esse quadro e, por isso, para explicar um pouco mais sobre o assunto, realizamos uma entrevista com o Dr. Fábio Pires, médico hematologista do Hospital Israelita Albert Einstein. Confira!    Hosts: Bárbara Fernandes e Amanda Oliveira                      Site: https://www.abrale.org.br/                Instagram: www.instagram.com/abraleoficial/                Youtube: www.youtube.com/AbraleSP                Facebook: www.facebook.com/abrale                Twitter: https://twitter.com/abraleoficial              Tiktok: https://www.tiktok.com/@abraleoficial

In a replay of episode #90 from 2019, we re-review a recent report from the CTOTC-04 study group assessing the impact of novel anti-rejection approaches which generally markedly reduce or remove steroids in the prevention of rejection. How are rejection rates affected by such an approach? Did incidences of diabetes or PTLD differ when using this form of steroid reduced approach in the 'low immunological risk' subset of patients undergoing heart transplantation? We speak with the first author of this work, Professor of Pediatrics, Dr. Jacqueline Lamour of the Icahn School of Medicine at Mount Sinai. Dr. Lamour provides deep insights this week! doi: 10.1016/j.healun.2019.06.006

Jill's guest is Lisa Davis, aka Litecoin Lisa. Litecoin Lisa is rocking the Cryptocurrency world and beyond with her informative videos on her Youtube channel, which also covers everything from health to politics to cryptos to woo woo and more! Litecoin Lisa also has a Patreon site where people can join and be part of a community while receiving all the Crypto scoop from her.  Check out her podcast, "The New Normal." "The New Normal," is Lisa's podcast on YouTube which began pre-Covid, and airs live every weekday at 5 pm Central time. 12 years ago Lisa founded a non-profit to serve kids in foster care which quickly became the largest volunteer effort in the state of Oklahoma. The non-profit  partnered with the community to make sure that no child is without a gift every Christmas. This is how Lisa met three of her children. Her youngest two, "the twins", were both born with only half a heart (Hypo-plastic Left Heart Syndrome) caused from drug exposure while they were in their mothers womb. She quickly learned to be a caregiver for medically fragile kids and an advocate for organ donation. She lived in the hospital with her youngest daughter during the first few months of her life until she received her gift of a new heart. Sadly, her daughter passed away after she developed cancer (PTLD) from the anti rejection meds that she had to take to keep her body from attacking her new heart. Lisa started a 501c3 Non Profit charity to honor her daughter. Lisa is married to her best friend and true partner in life.  They both got "RED PILLED"and began their Crypto journey when Lisa's mother gifted the newlyweds some Litecoin Cryptocurrency.  Litecoin Lisa was launched and her Crypto mission began to unfold.  Lisa likes that the Cryptocurrency movement is one of inclusiveness.  As more people get into Crypto, more people will benefit, and "we all rise together."In this episode, Litecoin Lisa outlines the workings of Cryptocurrency and the blockchain.   Lisa describes the concept of Cryptocurrency, like Bitcoin and Litecoin as being "mined." The idea of "labor" or energy with Bitcoin or Litecoin is connected to the "mining." There's a scarcity of Bitcoin, just like there is a scarcity of silver or goid, which gives it value.   LItecoin Lisa distinguishes Cryptocurrency from traditional banking systems.  Unlike banking, Bitcoin is not centralized, meaning one entity does not decide what Bitcoin is worth.  Thus, Cryptocurrency is decentralized so there is no "double spent" situation as with other currencies. One of the benefits of Cryptocurrency is that it removes central banks from managing the money supply as they reduce the value of money via inflation.  Bitcoin and blockchain technology has a decentralized processing and recording system even more secure than traditional recording systems.  Bitcoin is a peer-to-peer currency exchange, eliminating a middle man and has minimal fees.  Bitcoin, and Cryptocurrency has been the best performing asset in the last decade, and adoption has more than doubled in the past six months. Bitcoin, Litecoin and Digibites are true cryptocurrencies, while other "cryptos" are tokens. Follow Lisa Litecoin on her Patreon site, her Youtube channel and through her podcast!

In this special AYA episode, guest host Montana Skurka connects with Amanda Saunders, who 13 months after having a heart transplant was diagnosed with post-transplant lymphoproliferative disorder (PTLD). The two discuss what life is like living with a rare blood cancer while completing university and living through a pandemic.

NEW BOOK DISCUSSION ON GUT HEALTH & LYME RELATED EATING DISORDERSThank you for joining me for another discussion on your book, Recovery from Lyme Disease, The Integrative Medicine Guide to diagnosing and treating tick-borne illness.  Dr Kinderlehrer bio:Dr. Daniel Kinderlehrer is a Lyme Literate internist in Denver CO. After completing a residency in Internal Medicine in 1979, he opened one of the first practices in the US in what was then called Holistic Medicine. After becoming an expert in nutrition and environmental illness, he became ill himself with Lyme disease complex. His long road to recovery has given him insights into what patients are going through; his background in internal medicine trained him to understand the complexities of his multi-systemic illness; his knowledge of environmental illness has enabled him to evaluate immune dysregulation; and his study of energetic medicine, spiritual alignment, and healing from trauma has yielded insights into how to help patients shift their belief systems to being well.  Recovery from Lyme Disease is by far the most thorough book available on Lyme Disease Complex. It will provide patients with information that will guide them on their healing journeys, as well as supplying doctors with instruction on appropriate diagnosis and treatment approaches.  Dr. Kinderlehrer enjoys teaching his patients and the medical community, and we are honored to host him again!His book is available on Amazon in March, please don't forget to leave a review.How do you identify a Lyme related eating disorder? What are they? anorexia, bulimia...How do you treat them?What are the tests you order for someone with Lyme and GI problems?How do you treat the GI problems? What Binders do you use? Most GI doctors I've encountered recommend an immune modulator like Humera for intestinal bowel disease/syndrome.  Can this cause problems with a patient who is undiagnosed Chronic Lyme Complex?How common is GI problems in Lyme patients?What's your best hope for anyone reading your book?Intro18 minutes Impact of stress on immune system19:28 epigenetics20 antibiotics & microbiome21 inherited obesity and PTSD23 Healing ecosystem24 candida and enzymes27:39 Bartonella and Babesia influence on the gut29 parasites30 behavioral problems 32 Crohn's & biologics33 Research needs on treatments and diagnosticsHonoring all clinicians and researchers treating Lyme, THANK YOU!Please subscribe to our channel and like this video to support our work.  If you like my content and work, consider supporting it with a donation to https://www.texaslymealliance.net/donate.html.  There are podcasts of these interviews also on all major channels.  Thanks for joining us and we support your HEALING, YOU CAN!Support the show

NEW BOOK DISCUSSION ON PANS/PANDAS, MCAS, FOOD TRIGGERSRecovery from Lyme Disease, The Integrative Medicine Guide to diagnosing and treating tick-borne illness.  Dr Kinderlehrer bio:Dr. Daniel Kinderlehrer is a Lyme Literate internist in Denver CO. After completing a residency in Internal Medicine in 1979, he opened one of the first practices in the US in what was then called Holistic Medicine. After becoming an expert in nutrition and environmental illness, he became ill himself with Lyme disease complex. His long road to recovery has given him insights into what patients are going through; his background in internal medicine trained him to understand the complexities of his multi-systemic illness; his knowledge of environmental illness has enabled him to evaluate immune dysregulation; and his study of energetic medicine, spiritual alignment, and healing from trauma has yielded insights into how to help patients shift their belief systems to being well.  Recovery from Lyme Disease is by far the most thorough book available on Lyme Disease Complex. It will provide patients with information that will guide them on their healing journeys, as well as supplying doctors with instruction on appropriate diagnosis and treatment approaches.  Dr. Kinderlehrer enjoys teaching his patients and the medical community, and we are honored to host him again!His book is available on Amazon in March, please don't forget to leave a review.Q&A1. What is PANS/PANDAS?2. What are some common symptoms & behavioral issues people might see with it?3. Are these individuals common targets of misunderstandings?4. What is the best treatment for PANDAS discussed in your book?5. How do you manage pain for these patients?  CBD, THC, Advil, ibuprofen, detox baths?6. Can adults have PANDAS?7. How does MCAS play a role in PANDAS and Lyme Disease Complex, and how do you lower histamine?Introduction to the topics.19:40 Kristina's family experience with seizures from undiagnosed bartonella infection. 20 How to understand chronic illness in our community.28 PANDAS resources for support30 "Brain on fire" symptom and support, neuropathy33 MCAS34 "herx is NOT GOOD!" -DK41 Diet for PANS and cooking for the family, mention of Dr K's Mom's cookbook!45 "Speak with your money"- KB46 "Power to the patients, you can heal!" -KBPlease subscribe to our channel and like this video to support our work.  If you like my content and work, consider supporting it with a donation to https://www.texaslymealliance.net/donate.html.  There are podcasts of these interviews also on all major channels.  Thanks for joining us and we support your HEALING, YOU CAN!Support the show

The You Cannot Fail Rare Disease podcast series was created so that the Boomer Esiason Foundation can shine a spotlight on other people and organizations in the rare disease community. In the second episode, Swapna Kakani discusses dealing with post-transplant lymphoproliferative disorder after her small intestine organ transplant. In June 2014, after checking a few things off of her bucket list, Swapna decided that she was ready to have a small intestine transplant and to deal with the complications that often accompany an organ transplant. Tune in to learn more about Swapna’s transplant journey. 
 This video podcast series was made possible through an unrestricted educational grant from Atara Bio to the Boomer Esiason Foundation.

Dr Nimish Shah presents a short podcast on the BSH Guideline Frontline Management of Post-Transplantation Lymphoproliferative Disorder in Adult Solid Organ Recipient Patients.  Dr Shah discusses the guideline in three parts: 1) PET scan and its role in PTLD 2) The management of PTLD 3) Potential new developments   This document is an updated guideline and details the recommendations for the frontline management of adult patients with an established diagnosis of post‑transplant lymphoproliferative disorder (PTLD) following solid organ transplantation (SOT). PTLD represents a spectrum of disorders resulting from lymphoid or plasmacytic cell proliferations that occur as a result of immunosuppression following SOT. In adult SOT recipients, PTLD is the second commonest malignancy after skin cancer and is the commonest cause of cancer-related mortality1. The reported incidence varies according to patient age, transplant type and the degree of immunosuppression. Historically, PTLD has been reported to occur most frequently in the first year following transplantation. However, more recent reports suggest that PTLD occurring late (beyond the first year) may be at least as common2–5 Dr Nimish Shah is a Consultant Haematologist at the Norfolk and Norwich University Hospital NHS Foundation Trust.

In episode 45 Jason and Matthew speak with long time activists and twins, Jason and David Carmel. David was injured over two decades ago while vacationing in Mexico. He has gone on to achieve a successful career in biotech. Jason is a PhD / MD researcher at Columbia University researching activity based therapies and electrical stimulation. Their unique connection as twins weaves in and through the conversation for a unique perspective on their journey, work and activism after SCI. -- David A. Carmel Mr. Carmel is the senior vice president of public affairs and communications of eGenesis and is responsible for external outreach efforts to advocacy organizations, professional societies, policy makers, and investors. Prior to joining eGenesis, Mr. Carmel served as vice president in medical affairs and strategic alliances at Atara Biotherapeutics, where he helped to advance tab-cel® (tabelecleucel), which is in Phase 3 development for post-transplant lymphoproliferative disease (PTLD), an aggressive cancer that affects patients who have received a solid organ or bone marrow transplant. Earlier, he was co-founder and principal of Carmel Asset Management, an investment partnership where he was responsible for life science investments. Previously, he held positions in public affairs and business development for StemCyte, Pfizer, and Johnson & Johnson. Mr. Carmel served as the White House Fellow for the Secretary of the Treasury from 2002 to 2003. Mr. Carmel was appointed by Governor Andrew Cuomo to the New York Life Science Advisory Board. He is a founding board member of the New York Stem Cell Foundation, a former member of the New York State Spinal Cord Injury Research Board, and a Henry Crown Fellow of the Aspen Institute. He worked on the California Stem Cell Research and Cures Initiative, which provided $3 billion to fund stem cell research. He earned a bachelor’s degree, magna cum laude, from Harvard College and an MBA with a certificate in health care from the Stanford Graduate School of Business. Jason B. Carmel, M.D., Ph.D. -Weinberg Family Associate Professor of Neurology (in Orthopedics) -Executive Director, Weinberg Family Cerebral Palsy Center -Director, Movement Recovery Laboratory -Columbia University Vagelos College of Physicians and Surgeons -Columbia Translational Neuroscience Initiative Scholar Dr. Carmel received his B.A. in Human Biology from Stanford University and his MD from Columbia University’s College of Physicians and Surgeons. While in medical school, his identical twin brother suffered a spinal cord injury. This lead him to pursue basic science research. He completed a PhD with Wise Young, MD, PhD at Rutgers University. He then finished his medical training in Child Neurology at Columbia and is Board certified in this area. He completed a postdoctoral fellowship with Jack Martin, PhD, in neural control of movement. Dr. Carmel’s laboratory work at Columbia University Irving Medical Center is focused on the recovery of movement after injury to the central nervous system. The laboratory focuses on how the brain and spinal cord partner for movement through their motor and sensory connections. The laboratory is dedicated to repairing brain-spinal cord connections using activity-based therapies, including electrical stimulation and motor training. The approach capitalizes on the fact that most brain and spinal injuries preserve some of these connections. Spared connections become more numerous and stronger when activity is applied. This approach has shown promise in rat models of cerebral palsy, stroke, and spinal cord injury. Dr. Carmel sees patients with cerebral palsy and other neurological conditions affecting movement. The target neurological impairments include hemiplegia and spastic diplegia. Combining laboratory science and clinical medicine, he seeks to restore function through repair of the nervous system.

This week we review a recent report from the CTOTC-04 study group assessing the impact of novel anti-rejection approaches which generally markedly reduce or remove steroids in the prevention of rejection. How are rejection rates affected by such an approach? Did incidences of diabetes or PTLD differ when using this form of steroid reduced approach in the 'low immunological risk' subset of patients undergoing heart transplantation? We speak with the first author of this work, Professor of Pediatrics, Dr. Jacqueline Lamour of The Albert Einstein College of Medicine. Dr. Lamour provides deep insights this week! doi: 10.1016/j.healun.2019.06.006

This week we review a recent report from the CTOTC-04 study group assessing the impact of novel anti-rejection approaches which generally markedly reduce or remove steroids in the prevention of rejection. How are rejection rates affected by such an approach? Did incidences of diabetes or PTLD differ when using this form of steroid reduced approach in the 'low immunological risk' subset of patients undergoing heart transplantation? We speak with the first author of this work, Professor of Pediatrics, Dr. Jacqueline Lamour of The Albert Einstein College of Medicine. Dr. Lamour provides deep insights this week! doi: 10.1016/j.healun.2019.06.006

To honor Organ Donation Awareness Month, Marge Carfora, 36 with cystic fibrosis and 14 years post double lung transplant, joins the podcast as the first ever resident guest host! Marge will feature on all the podcasts airing in the month of April. This episode tells most of Marge's life story, from diagnosis right after birth, through college, a double lung transplant in a time before the Lung Allocation Score, marriage, surviving three different types of cancer - Posttransplant lymphoproliferative disease (PTLD), cervical cancer and breast cancer - and finally becoming a mother to twins! Marge talks about overcoming each obstacle, one at a time and using her attitude as the ultimate force driving her through each complication.

Austin was diagnosed with Burkitt lymphoma PTLD in April 2017. This is a rare, aggressive form of Burkitt lymphoma which results from the immunosuppression that is required following an organ transplant. In 2011, when Austin was 3 years old, he had a severe E.coli complication called hemolytic uremic syndrome which led to kidney failure, so he underwent a kidney transplant. Austin recovered from the successful transplant and had been doing well for a few years, but in April 2017, he began to complain of pain from urinating. The pain was so severe he collapsed at school. Austin's parents, Ben and Cortney, rushed him to the hospital and insisted that he have scans done – the scans revealed a baseball-sized mass near his bladder and another mass in his liver. Further testing and a biopsy determined that Austin had developed Burkitt lymphoma PTLD as result of his earlier liver transplant. Austin's family was moving from LA to Boston at the same time he was diagnosed, so they decided to pursue treatment at Dana-Farber. Austin then had 4 rounds of intense chemotherapy, including 8 lumbar punctures, and had to be hospitalized for each round. Between the beginning of May through the first week of July, he spent more than 50 days in the hospital – but Austin just completed treatment. Cortney says that their family is very grateful for the Dana-Farber treatment team's swift, smart and strategic treatment plan for Austin. They couldn't imagine a better place for him to be treated than Dana-Farber, which is one of the only hospitals with PTLD specialists. Austin attends Lincoln Street Elementary and enjoys Pokémon, baseball, and Minecraft. Austin recently met Brock Holt during Brock's visit to the Jimmy Fund Clinic –they sent a selfie to Dustin Pedroia, Austin's favorite Red Sox player! His family includes his mom Cortney, dad Ben, sister Emma, 9, and brother Henry, 3.

Prof Tarella talks to ecancertv at ASH 2015 about an international phase II trial that shows response to rituximab induction is a predictive biomarker in post-transplant lymphoproliferative disorder (PTLD) and allows successful treatment stratification. He also discusses a long-term survey of 597 patients, showing that life expectancy in follicular lymphoma is mainly determined by response to first-line treatment.

Julia and I welcome Luke Doherty, 26 with cystic fibrosis from Dublin, Ireland, to the podcast this week. Luke talks his recent journey through a double lung transplant, which has needed to include chemotherapy treatment for PTLD. To that end, we talk about some of the differences between the American and Irish transplant listing procedures. Luke mentions that despite his failing health prior to transplant, he made fitness a priority in his life and he ultimately credits that to an initial speedy recovery. As you will find out, fitness is a major part of his life, to the point where it serves as a way for him to find a release from the challenges of CF. Luke is still very much in recovery from his transplant thanks to the PTLD, but he is making strides everyday to return to his life as a personal trainer.

Thu, 1 Aug 2013 12:00:00 +0100 https://epub.ub.uni-muenchen.de/24135/1/oa_24135.pdf Trappe, Ralf Ulrich; Leblond, Veronique; Riess, Hanno; Striefler, Jana K.; Valentin, Angelika; Moore, John; Dreyling, Martin H.; Dierickx, Daan; Choquet, Sylvain; Zimmermann, Heiner

Background. Posttransplantation lymphoproliferative diseases (PTLD) are mainly Epstein-Barr virus (EBV)-associated disorders of B-cell origin. Due to the rarity of monomorphic T-cell PTLD (T-PTLD), knowledge about pathogenesis, risk factors, therapy, and prognosis relies predominantly on case reports and small series. Therefore, we aimed to provide an overview and a retrospective analysis of this rare PTLD subtype. Methods. We analyzed all available articles on T-PTLD in the PubMed database as well as in our own databases (Institute of Pathology/Department of Paediatric Haematology and Oncology, Hannover Medical School) from 1988 to 2010. Reevaluated parameters were gender, age, transplanted organ, immunosuppressant regimen, time between transplantation and T-PTLD manifestation, T-PTLD subtype, virus positivity, localization, therapy, and follow-up. Results. A total of 163 cases were evaluated. We found that hematopoietic stem cell transplantation was associated with early-onset T-PTLD, whereas late onset occurred after immunosuppression with steroids and azathioprine without administration of calcineurin inhibitors. The major independent favorable prognostic factors were T-PTLD of the large granular lymphocytic leukemia subtype, young age, and a combination of radiotherapy/radiochemotherapy and reduced immunosuppression, whereas the hepatosplenic T-cell lymphoma subtype and cases with involvement of bone marrow, the central nervous system, or graft had an adverse prognosis. Conclusion. T-PTLD is a heterogeneous group of different aberrant T-cell proliferations and represents a significant complication following transplantation, showing a uniformly poor prognosis.

Patients after solid organ transplantation (SOT) carry a substantially increased risk to develop malignant lymphomas. This is in part due to the immunosuppression required to maintain the function of the organ graft. Depending on the transplanted organ, up to 15% of pediatric transplant recipients acquire posttransplant lymphoproliferative disease (PTLD), and eventually 20% of those succumb to the disease. Early diagnosis of PTLD is often hampered by the unspecific symptoms and the difficult differential diagnosis, which includes atypical infections as well as graft rejection. Treatment of PTLD is limited by the high vulnerability towards antineoplastic chemotherapy in transplanted children. However, new treatment strategies and especially the introduction of the monoclonal anti-CD20 antibody rituximab have dramatically improved outcomes of PTLD. This review discusses risk factors for the development of PTLD in children, summarizes current approaches to therapy, and gives an outlook on developing new treatment modalities like targeted therapy with virus-specific T cells. Finally, monitoring strategies are evaluated.

EBV ist ein Herpesvirus, welches in über 90% aller Erwachsenen nachgewiesen werden kann und in den wenigsten Fällen Beschwerden verursacht. Unter bestimmten Umständen kann es aber zur Ausbildung einer Infektiösen Mononukleosekommen und auch an der Entstehung einer Reihe von Krebserkrankungen, allenvoran die PTLD (posttransplant lymphoproliferative disease), das Burkitt- und das Hodgkin-Lymphom, ist EBV ursächlich beteiligt. Trotz zahlreicher Bemühungen und einiger vielversprechender Ansätze ist bis heute kein wirksamer Impfstoff gegen das Epstein-Barr Virus vorhanden. Im Bereich Exosomen als Mittel zur Induktion von Immunantworten wird seit gut 10 Jahren geforscht und ihre Wirksamkeit konnte bereits in klinischen Studien zur Behandlung mehrerer Krebsarten getestet werden. In dieser Doktorarbeit wurden HEK 293-Zellen und ein auf diesen Zellen basierendes Verpackungssystem für virale Vektoren auf ihre Eignung hin untersucht, rekombinante Exosomen und Virus-like-Particles (VLPs) zu produzieren, welche eventuell als DNA-freies Vakzin gegen EBV eingesetzt werden könnten. In EBV-positiven Verpackungszelllinien konnte durch Induktion des lytischen EBV-Zyklus die Freisetzung DNA-freier VLPs erreicht werden. Genau wie Exosomen aus 293-Zellen, die zuvor mit Expressionsplasmiden für EBV-Antigene transfiziert worden waren, konnten sie aus dem Zellkulturmedium aufgereinigt werden. Ihr großes immunogenes Potential zeigte sich bei der Reaktivierung von EBV-spezifischen TZellklonen und Gedächtnis-T-Zellen aus PBMCs, wo bereits geringe Mengen für eine Stimulation ausreichten. Zu der hohen Effizienz der Partikel trug ihr Tropismus bei, der auf virale Glykoproteine, vor allem gp350, zurückzuführen war. Die Partikel besaßen dadurch eine Affinität zu B-Zellen, über die effizient die Präsentation der Exosomen und Virus-like-Particles erfolgte. Auch in in vivo-Versuchen, bei denen mit dem hu-PBMC-Rag-Mausmodell und dem MHV-68-Mausmodell gearbeitet wurde, konnten durch Immunisierung mit Exosomen bzw. Virus-like-Particles virusspezifische humorale wie zelluläre Imunantworten ausgelöst werden. In Stimulationsexperimenten von malignen Zellen aus Patienten mit chronisch lymphatischer B-Zellleukämie (B-CLL) konnte ich weiterhin zeigen, dass Exosomen und VLPs auch als Überträger funktioneller Moleküle wie den CD40L, einem Mitglied der Tumor-Nekrose-Faktor-Familie, fungieren können. Dieser bewirkte in den sonst nicht immunogenen und deshalb vom Immunsystem nicht erkannten CLL-Zellen eine verstärkte Expression kostimulatorischer, Adhäsions- und apoptoseassoziierter Moleküle. Auf diese Weise war es möglich, autologe Tumor- und EBV-spezifische T-Zellen zu reaktivieren. Exosomen und Virus-like-Particles könnten deshalb bei der Behandlung der B-CLL eine vielversprechende Alternative zur Gentherapie darstellen.

The Epstein-Barr virus (EBV) is associated with a number of human malignancies. Following primary infection, the virus persists lifelong in the infected host by latently infecting B cells and occasional cycles of reactivation, virus production and re-infection. Adoptively transferred EBV-specific T cells, generated by repeated stimulation with autologous lymphoblastoid cell lines (LCL) in vitro, are able to cure post-transplant lymphoproliferative disease (PTLD). However, the generation of these vaccines is labor and cost intensive precluding their general availability for all patients at risk. Novel insights into the mechanisms of protective antiviral immunity is expected to provide a better understanding of the pathogenesis of EBV-associated diseases and to facilitate the development of novel and generally available immunotherapeutic options. The aim of this work was to assess specificity and breadth of the EBV-specific T helper cell response, using two different experimental strategies. To define specificity, LCL-stimulated CD4+ T cell lines were established from 23 EBV-negative and -positive donors. The T cell lines generated from EBV-negative donors responded poorly against LCL and failed to show EBV-specificity. By contrast, all T cell lines established from healthy virus carriers were EBV-specific. Half of the lines from acutely EBV-infected patients with infectious mononucleosis (IM) were also EBV-specific, while the other half recognized EBV-positive and EBV-negative target cells. Unexpectedly, the EBV-specific T cell lines did not recognize latent antigens of EBV expressed in all LCL. Instead, these lines were specific for lytic cycle antigens predominantly derived from virion proteins. Several of the T cell lines recognized BNRF1, a viral tegument protein. Most T cell lines, however, recognized different virion antigens, suggesting that the family of virion proteins forms the immunodominant targets of the EBV-specific T helper cell response. Studies on the breadth of the EBV-specific T helper response demonstrated that all healthy virus carriers maintain CD4+ T cell memory to lytic cycle antigens. T cells specific for virion antigens recognized EBV-positive cells directly and, surprisingly, a much higher percentage of target cells than those expressing lytic cycle proteins. Antigen was efficiently transferred to bystander B cells by receptor-mediated uptake of released virions, resulting in recognition of target cells incubated with less than one virion per cell. T cell recognition did not require productive infection and occurred early after virus entry before latency was established. By secreting perforin and granzyme B upon antigen recognition, virion-specific T helper cells inhibited proliferation of LCLs and suppressed the outgrowth of LCLs following infection of primary B cells with EBV. These results established a novel role for virion-specific T helper cells in the control of EBV infection, and identify virion proteins as important immune targets. The findings have implications for the treatment of diseases associated with EBV and potentially other coated viruses infecting MHC class II-positive cells.