With the start of a new year, we find ourselves with time to reflect on the year we have all just experienced. 2022 brings with it a hope that conditions around the world will now improve with a concerted global vaccination program having been underway for some time. It is more important than ever to reflect on the past, its achievements and stay connected within our community.
It is most certainly an exciting time for the xenotransplantation field. We have started this year as we ended the last, with exciting news of clinical xenotransplantation becoming a reality. Some massive steps forward have occurred, with our amazing new technologies helping us to achieve what was, for many years, a dream for many of us in the field. We have worked hard to achieve these results and to see the work push forward, from New York with the TG pig kidney transplants into brain dead patients to Baltimore transplanting a patient with a 10 gene modification pig heart, is incredible. We need to also acknowledge the support of government authorities such as the FDA to have supported these life changing transplants. These breakthroughs show how hard we have worked with the IXA, TTS and the WHO in the regulatory sphere to develop guidelines and legislation to support and make this possible. These successes are the validation for our efforts. We can look forward to a very exciting 2022 as well as an amazing future with these incredible leaps forward.
One of the other major highlights of the past year was that we were able to hold a very successful joint Virtual IXA/CTRMS Congress in 2021 and I am pleased to provide a summary of the meetings highlights.
There was a total of 311 registrants. Participants were from ten different countries with many participants attending from North America, making up 56% of the attendees.
There were 11 plenary speakers with a total of 18 parallel session speakers, three industry speakers and nine networking panellists. Of the total 74 abstracts accepted for presentation, there were 50 oral abstracts, 16 mini-oral abstract and five e-poster abstracts presented. We congratulate and thank all the presenters. A special thanks goes to the 39 session moderators who helped facilitate the meeting run smoothly.
One of the highlights of the meeting for myself personally was to announce and present the IXA award winners for 2021. It was indeed a pleasure to announce the following winners:
2021 Agnes Azimzadeh Award - Rita Bottino
2020 Xeno Prize - Arne Hinrichs and Evamaria O. Riedel
Corbin Goerlich - Select Life-Supporting Multi-Gene Cardiac Xenografts from Swine Demonstrate Survival >8 months in Baboons, with Implications for Human Clinical Trials
Takayuki Hirose - Graft Survival of The Kidney Xenografts with Triple Xenoantigen Knockout and Multiple Human Transgenes in Cynomolgus Monkeys
Adwin Thomas - Efficacy and safety of relevant immunosuppression in non-human primate neonatal islet cell cluster xenotransplantation
Konrad Fischer - Immunological characterisation of multi-knockout pigs
Margaret Connolly - Lung and liver platelet sequestration is attenuated by humanization of von Willebrand factor in ex vivo xenoperfusion studies
I also will take this time to acknowledge and thank the entire TTS management team for their hard work, forward planning, and skill in helping us to run such a successful meeting.
The past two years have seen some very dramatic changes in the way we have interacted, lived, and done business both at home and around the globe. Confinement measures and travel restrictions remain in effect in many countries, including our own to limit the continuing waves of COVID-19 infections.
My thoughts go out to all those who are affected by this pandemic. I would like to draw attention to and give thanks to the many caregivers and the medical community, who continue to fight for our patients courageously and passionately and for our communities, placing the life of others ahead of their own.
You are all no doubt looking forward to the advent of a very successful year, as am I, where we may be able to meet in person at one of the various scientific meetings planned for this New Year.
Professor Wayne J. Hawthorne
Newsletter and Communications
Dr. Jay A. Fishman
Associate Director, MGH Transplant Center
Massachussetts General Hospital
I have been asked to take on the IXA Newsletter and Communications on behalf of the IXA Council in place of Rita Bottino who has provided expert leadership over recent years and who has taken on the role of Secretary-Treasurer of IXA. On behalf of the Society, many thanks to Rita for her hard work!
The IXA Newsletter should reflect the interests of the membership – and serve to invite new members from the many clinicians and scientists involved in xenotransplantation, notably as clinical trials emerge. As we think about new ways to communicate the excitement surrounding xenotransplantation, I invite our members to offer advice and content for future newsletters (firstname.lastname@example.org). We will be reaching out via podcasts and other social media in the future. Many thanks for your participation!
Best wishes for 2022!
Infectious Disease Committee
Advancing Xenotransplantation to the Clinic: Infectious Disease Challenges
As preclinical and clinical studies advance, as well as generation of swine as potential source animals for clinical xenotransplantation, the US Food and Drug Administration (FDA) has issued a revised PHS Guideline on Infectious Disease Issues in Xenotransplantation (Docket No. FDA-2012-N-0559) for comments by the public (Public Health Service (PHS) Guideline on Infectious Disease Issues in Xenotransplantation). These proposed guidelines have raised a series of thoughtful considerations regarding the safety challenges posed by clinical xenotransplantation. As is generally understood, the risk for infection will be related to the intensity and duration of immunosuppression deployed in a specific xenotransplantation regimen that will be defined for each specific protocol. This proposed guideline discusses (1) The development of xenotransplantation clinical protocols; (2) the preparation of submissions to FDA; and (3) the conduct of xenotransplantation clinical trials. Under the proposal, record-keeping/clinical data would be maintained in a cross-referenced system that links the relevant records of the xenotransplantation product recipient, xenotransplantation product, source animal(s), animal procurement center, and significant nosocomial exposures. These records and blood and tissue samples would be maintained for 50 years. The PHS guideline also describes an occupational health service program for the protection of health care workers involved in xenotransplantation procedures, caring for xenotransplantation product recipients, and performing associated laboratory testing. The duration of maintenance of clinical records and samples is extrapolated from experience with Human immunodeficiency virus (HIV) and Human T-lymphotropic virus (HTLV) and hepatitis C virus – which may have prolonged latency. It may be worth noting that such exogenous human viruses have a much shorter latency in immunosuppressed allotransplant recipients and that for HIV and HCV, antiviral therapies have emerged that impact the course of infection. The likelihood of infection by comparable endogenous retroviruses of swine (or unknow porcine viruses) remains unknown.
The guideline poses some important practical questions:
Who are the best candidates for initial trials of clinical xenotransplantation? And who might be excluded by virtue (e.g.,) of preexisting immune deficiency in the recipient or their social contacts? How might children be considered as candidates?
How should infectious disease surveillance be performed for recipients and clinical staff involved in organ procurement, transplantation, and clinical care? How should infectious disease surveillance be performed for source animal caretakers? Assuming universal and contact precautions are deployed, how would needlestick or laceration injuries be handled?
Which samples (blood cells, sera) should be stored against future epidemiological investigations? And from who?
Who has access to such data and samples? And which tests are performed routinely and for “cause”?
Who should develop and maintain a central database to catalog samples and patient data for up to 50 years (when most of the clinical sponsors, patients and clinical staff may no longer be available)?
Many of these questions will merit discussion among investigators on an international basis – as was done under the auspices of the World Health Organization in the past. The IXA will continue to be engaged in these discussions as clinical application of xenotransplantation develops.
Jay A. Fishman, M.D.
Boston, MA, USA
Chair, IXA Infectious Disease Committee