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Prospectus

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Cellular therapies

Course
2020-2021

Admission requirements

Dutch students can enroll for a half minor if they have obtained 60 credits from the first year. Admission to a specific minor is based on motivation letters and a preferred choices and where needed lottery system.

International Students should have an adequate background in Medicine and can be admitted on the basis of CV and motivation letter. For more information, please contact internationalisering@lumc.nl.

Description

The minor ‘’Cellular Therapies’’ will answer the following questions:
Why are blood transfusions and pregnancies usually well accepted by the patient’s immune system? Why, in contrast, is rejection of hematopoietic stem cells and organ transplants (even of close relatives), a very real danger which sometimes needs aggressive immune suppression ? What are the symptoms, dangers and therapies when so called alloimmunisation, graft versus host disease or rejection do occur in the mentioned conditions? What can we do about it e.g. by donor selection. In summary, how is our immune system enabled to make choices between attacking or accepting cells, tissue or organs.
How can new state of art flowcytometry help us to monitor the normal state and development of the immune-system vs it being changed by cancer or as response to pathogens or allogeneic tissue and cells? What is needed to start thinking about the use of ex vivo manipulated living cells for regenerative therapy?

What defines a stem cell, what different kinds are there? How can stem cells be used now and in the future and what would be reasonable time lines for their high promise? What medical – ethical, financial but moreover safety caveats need to be discerned and are there solutions?

How are autoimmune diseases (such as diabetes type 1, rheumatoid arthritis, and inflammatory bowel disease), and immune tolerance-related complications of stem cell and organ transplantation explained and what therapies could be effective? What are the possible pro´s and con´s (risks) of the classical versus the new tolerogenic cell therapies.

Cancer and serious infections signify lost or insufficient immunity. What are nowadays and possible future developments in immune-activating cell therapies and how do they compare with classical therapies to treat cancer and infections? What do we need to make these therapies more effective and work in collaboration?

What do different stakeholders: patient, physician, donor, scientist, regulatory board member, expect new cellular therapies to be. How to implement these therapies as efficient and safe as possible from bench to patient. Can we use animal models, do we need to know the full therapeutic mechanism, what do we monitor in patients and what are parallels with (the history) of classical blood transfusions and hematopoietic stem cell transplants?

Course Objectives

  1. Analyse the symptoms and pathophysiologic mechanisms of low, deficient or dysfunctional blood and immune cells with history taking and diagnostics

  2. Describe current therapies for patients who have cancer, persistent infections, bleeding, autoimmune disease, transplant rejection or disorders in pregnancy and indicate why and when new cell therapies are needed and which research is still needed

  3. Identify risks of therapies and design quality system components that safeguards optimal safety in donor assessment, production and clinical study design of cell therapies

  4. Explain and Compare the critical phases in the development of existing therapies and their remaining problems (Clinical time line ) with new cell therapies (Translational time line) and or envision the most likely development of the latter and what is needed to stimulate this development

  5. Teach and educate fellow students on the issues of the course in an interactive and responsive way.

  6. Discern faults and omissions in a cell therapy study proposal; be able to generate improvements

  7. Interview patients and scientist physicians on their view of their disease of interest, the current treatment, the remaining needs and how cell therapies could help

  8. Collaborate with fellow students to yield original and synergistic results in assignments and practices

  9. Write a paper and prepare presentations

Timetable

All course and group schedules are published on our LUMC scheduling website or on the LUMC scheduling app.

Mode of instruction

Lectures, workgroups, patient interviews, clinical/ therapy related Self Study Assignments (SSA), exam, open questions, research project or clinical study protocol with pitch-presentation in groups of two students and preparing a you-tube MOOC like movie The assessment criteria for these assignments are described in a Rubik format, which is included in the module book.

Assessment method

General subject assessments:
The first assessment of this kind is in week 3: a written exam of max two hours consisting of mainly open and some MC questions on general subjects dealt with in weeks 1-3 . Answers on the open questions will be assessed on the basis of model answers and individual feedback is given.
In the so called ‘’improvement of a study proposal for a new cell therapy“ in week 9 (one of the a SSA) of max one-hour, again general subjects in cell therapies will be addressed and afterwards discussed.

These two assessments will aid in assessing the progress (or deficiencies) of students throughout the minor and specifically also to prepare for the final exam in week 10 (see below for information). The matrix assessment grade will form 10% of the total minor grade.

Patient and therapy oriented self assessment asignments (SSA):
Throughout the minor, students will get SSA in small groups of 2 and maximal 3 students. In this way at least 2-3 patient case/ disease problems – e.g. illustrated by scientific articles – will be addressed by these groups with new cell therapies in mind. From this, students need to prepare a 10-15’ presentation (e.g. around 10 ppt slides) or another form that can be individually scored. The presentation will be followed by a 5-10 min all student discussion/debate based on the presentation and pre-stated and by all students prepared questions.

Content of the presentation, and the answers and discussion in relation to stated questions are graded by both teacher/ tutor and preferably 2 students. The Rubric-category grading system (‘’poor/ improving/ good”) will help to structure feedback and thus improve in the different skills (e.g. information transfer, structure, knowledge, presentation skills) that are needed for a good presentation. In this way students will be prepared for the final pitch presentation in week 10.

Paper, pitch presentation and MOOC:
On the basis of the subjects dealt with in the ½ minor, as soon as possible but before week 4, several ‘2-students’ teams are formed and assigned to a tutor in order to eventually prepare a research project proposal or a clinical study protocol which at the end of the minor is presented in three forms: a paper (at least 4000 words), pitch presentation and you-tube MOOC-like movie (all due in week 10). A list of possible subjects for this project proposal or clinical trial will be made available to the students at the start of the ½ minor. Alternative subjects may be proposed, which however need to be approved by the minor management. Again all grading will be in agreement with Rubric evaluation matrices: all will constitute 60 % of the full minor grade (paper = 40%, pitch 13.3 % and MOOC 6.7 %).

Exam and open questions:
In week 10, knowledge from all themes focusing in particular on the content of week 4-9 is tested via an exam with MC- and open questions. Here, students are again tested in common themes connecting different concepts and therapies dealt with in the minor. The exam will constitute 30 % of the final grade.

Other assignments:
Several other assignments like ‘practice sessions’ or a debate serve as learning aids or ‘leermiddelen’ and are used to get feedback on competencies that are needed for the graded assignments.

Examination committee:
Prof. J.J. Zwaginga, Dr. T. Nikolic, Dr. P. Meij, Dr. M. Eikmans, Dr. T. Netelenbos, Dr. L.E.M. van Oosten, Dr. M. Schilham and others
The exam dates can be found on the schedule website.

Reading list

Papers will be provided per day-to-day schedule via Blackboard.

Registration

Contact

Prof. J.J. Zwaginga
LUMC, Department of Immunohematology
and Blood Transfusion
Email: j.j.zwaginga@lumc.nl

Dr. T. Nikolic
LUMC, Department of Immunohematology
and Blood Transfusion
Email: T.Nikolic@lumc.nl

Mw. A.N. Gunthardt
LUMC, Department of Immunohematology
and Blood Transfusion
Email: A.N.Gunthardt@lumc.nl

Remarks