Dates: 2 weeks in early October annually (E.g., September 30 – October 11, 2024)
PREREQUISITES AND PLACEMENT IN THE CURRICULUM:
Successful completion of the Phase 1 curriculum
Immunology advances rapidly, promotes biomedical/clinical research, and innovates fundamentals, which game-change medical practice from cutting-edge diagnosis to FDA-approvals of revolutionary therapeutics for diseases, particularly immunotherapy cure or remission of some previously untreatable cancers or other diseases.
Year 4 medical students with career interests will be attracted to this course “Advanced Immunology for Present/Evolving Therapeutics” for in-depth learning, critical thinking, skill-gaining and potential involving of those game-change immunotherapeutics or research. These aspects are important additions to the overall curriculum, providing comprehensive educational processes for clinical practice and career development.
Zheng W Chen, MD, PhD, Professor/Director
Maureen Richards, PhD. Assistant Dean
Fred Zar, MD, Professor/Director
Sam Pope, JD, PhD, Associate Professor
Topic #1: Unconventional T cells (γδ T/ MAIT/ NKT) versus conventional T cells (CD4/CD8) in immunity and therapeutics
- Describe how unconventional γδ T/MAIT/ NKT cells differ from CD4/CD8 T cells in T cell receptor repertoires, non-peptide antigens and associated presenting molecules.
- Understand attractive effector features of unconventional T cell populations: e.g. pleiotropic effector functions, MHC-independent cytotoxic killing of cancer cells and infected/diseased cells compared with CD8 T cells and NK cells.
- Describe how unconventional T cell populations play roles in homeostasis, immune responses/immunity or overreactive inflammation.
- Understand the immunity prototype in which non-peptide phosphoantigen-specific γδ T cells or others contribute to fast-acting (innate-like) mucosal immunity to infections.
- Describe the ability of γδ T cells/CD8/CD4 T cells to function as tumor-infiltration lymphocytes (TIL) that serve as clinical predictor of tumor outcome and discuss fundamentals for T cell transfer therapy for cancers.
Topic #2: The revolutionary T-cell Transfer Therapy (TIL/CAR T cells) approved by FDA for treatments of cancers and autoimmune diseases and for evolving therapy against infectious diseases (fundamentals and present/evolving therapeutics):
- Define TIL therapy and chimeric antigen receptor (CAR) T cell therapy in T-cell transfer immunotherapeutics.
- Understand and describe immune mechanisms whereby TIL and CAR T cells can recognize and attack cancer cells or diseased cells.
- Describe CAR T cell therapy procedures/CAR T cell program for generating CAR T cells for autologous infusion therapeutics against cancers and autoimmune diseases and discuss utility of evolving allogeneic CAR T cells.
- Understand clinical indications/usage of T cell transfer therapy for cancers and autoimmune diseases, describe CAR T cell therapy immune markers or parameters related to efficacy evaluations.
- Discuss the evolving CAR T cell therapy for anti-HIV/-HBV/-HCV/-CMV/-fungus treatments.
- Explain different treatment outcomes of CAR T cell transfer therapy in patients.
- Describe why CAR T cell therapy may induce major adverse reactions such as cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) and describe monitoring and management principles.
Topic #3: T cell exhaustion and Immune Checkpoint Inhibitors in present and evolving therapeutics in cancers/ autoimmune diseases/infections
- Define T-cell exhaustion and explain regulatory pathways including the newly discovered source in which T-cell exhaustion occurs in anti-cancer response or CAR T cell therapy or in persistent infections (HIV/HBV/HCV).
- Discuss immune checkpoint mechanisms whereby FDA-approved immune checkpoint inhibitors restore exhausted T cell effector function leading to anti-cancer immunity or pathogens clearance.
- Explain what cancers are treated with immune checkpoint inhibitors and describe how PD-1/PDL-1 and CTLA4 blockades serve as neoadjuvant immunotherapy with fully and partially successful cases in cancers.
- Discuss how immune checkpoint inhibitors treatments achieve detectable successes in infectious diseases.
- Describe side effects of immune checkpoint inhibitors as immunotherapy and discuss managing principles.
Topic #4: Trained immunity-based vaccines in broad-spectrum disease prevention and Treatment Vaccines.
Topic #5: Cytokine signals targeted as immune interventions in present/evolving therapeutics in cancers/ autoimmune diseases/infections
- Discuss innate-immune-cell heterologous “memory” protection (trained immunity) in contrast with classical vaccine memory immunity.
- Understand and discuss mechanisms whereby live-attenuated vaccines/infections confer broad trained immunity against infections/diseases in pediatrics and adults.
- Describe immune principles for treatment vaccines as approved by FDA for present/evolving therapy against cancers.
- Discuss targeted-therapy prototypes of cytokines/signals that mediate immune protection or disease consequence.
- Describe FDA-approved cytokines-targeted immune interventions in present/evolving therapeutics in cancers/autoimmune diseases/infections.
Topic #6: Nanobiotech-innovated medicines in immunity/therapeutics in cancers/infections/ autoimmune diseases
Topic #7: Engineered monoclonal antibodies (mAb) including bispecific Ab in immunity and therapeutics
- Understand and discuss biomedical aspects of nanobiotechnology, particularly the formulation/delivery of nano-medicines to targeted cells in immunity and therapeutics.
- Describe prototypes of nanobiotech-innovated products as approved by FDA for disease prevention and therapeutics as well as evolving applications against cancers/autoimmune diseases/infections.
- Discuss prototypes of FDA-approved engineered monoclonal mAb including bispecific Ab in present and evolving prevention and therapeutics.
- Describe immune mechanisms whereby engineered mAb work against cancers/infections/ autoimmune diseases.
- Discuss common side effects and managing principles of nanotech-innovated medicine and mAb-based products.
At the end of this experience the student should be able to:
- Apply the principles of advanced immunology and evidence-based medicine.
- Gain and consolidate skills/capabilities for in-depth learning and for presenting and evaluating publications/data in the context of present/evolving therapeutics, as engaged particularly through paper discussions and topics engagements.
- Understand common themes/experiences of patients and health professionals in immunotherapy-related aspects of anxiety, complexity, and distress/despair as well as mitigation strategies at an individual and structural level.
- Combine knowledge of immunological, biomedical, clinical, and cognate sciences as well as health ethics to meet the basic and clinical requirements that are relevant to the graduation competencies below.
The Advanced Immunology in Present/Evolving Therapeutics will be a Zoom-online only course. The two-week course will have multiple topics and each topic includes two days of modules/activities (2-3 hr. per day weekly): Day-one modules entail group-based in-depth learning activities in which all groups will watch short video(s) from the NIH/premier institutions/NIH-funded experts; each group will read/discuss group-specific paper(s)/theme questions while developing short PPT (<12 slides) presenting background/rationale/major findings/conclusive points in the paper(s) in the context of present/evolving immune therapeutics for the Day-two sharing and engagement; Day-two modules enable all groups/faculty to experience presentations and topic engagements in which representative(s) of each group present its PPT for sharing with other groups and for engagements of themes(questions) in the immune-clinical settings etc.
Students will be randomly divided into multiple groups based on the registered number. Since there will be 5 sessions for presentations/engagements, each group will have its own presenter rotation list for representative(s) to timely put together and present the main findings/points in PPT as discussed by the group on Day one. Faculty will involve daily, particularly will meet with students to instruct Day-two presentations/engagements. Office hours will also be offered daily to facilitate in-depth discussion and engagement. Based on course activities, students may write a reflection paper.
Through paper discussions and topics engagements, students are able to gain/consolidate skills/capabilities for advanced immunology learning and for presenting/evaluating publications/data in the context of present/evolving therapeutics. These skills/capabilities will facilitate students clinical/academic career development.
This is a Satisfactory/Unsatisfactory course. To pass the course, students must complete all assigned online modules, attend/participate in all online discussions/activities including mandatory presentations and engagement sessions. Students are also required to take turns to lead the development of PPT (<12 slides) during the group discussion of assigned papers/videos on Day-one modules and thereafter to present PPT for sharing with other groups and for engagement on Day-two modules. Any missed session may require a make-up assignment. If a student is unable to make their assigned session, they should reach out to discuss with assigned faculty member their progress that week. Students may write a reflective essay based on the course activities. Faculty will provide feedback comments to students. Students may submit completion certificates for any online modules where one exists.
Program Number: ELEC 537
Program Director: Zheng Chen, MD, PhD
Duration: 2 Weeks
Night Call: No
Students Accepted: Min. 5 Max. 35
Lectures/Conferences/Faculty hours per week: Approximately 12-18 hours per week
Laboratory hours per week: none
Independent Study hours per week: at least 30 hours of work will be done a week by students.
Inpatient hours per week: none
Outpatient hours per week: none
Total number of hours per week: varies
Number of weeks of credit: 2