Immunological & Biomedical Successes of Treating/Curing Refractory/Untreatable Diseases (NC) (NPF)*
2 weeks in early October annually (E.g., September 30 - October 11, 2024)
Intro Heading link
PREREQUISITES AND PLACEMENT IN THE CURRICULUM:
Successful completion of the Phase 1 curriculum
PURPOSE:
Immunology & biomedical research advance rapidly, promotes clinical innovations and lead to game-changing medical practice from cutting-edge diagnosis to FDA-approvals of revolutionary therapeutics including cure or remission of previously untreatable/refractory diseases.
Year 4 medical students with career interests will be attracted to this course “Immunological & Biomedical Successes of Treating/Curing Refractory/Untreatable Diseases” for in-depth learning, critical thinking, skill-gaining and potential involving in game-changing therapeutics or research. These aspects are important additions to the overall curriculum, providing comprehensive educational processes for clinical practice and career development.
Participating Faculty:
Zheng W Chen, MD, PhD, Professor/Director
Maureen Richards, PhD. Assistant Dean
Sam Pope, JD, PhD, Associate Professor
OBJECTIVES (Theme Questions):
Topic #1: T cell exhaustion and Immune Checkpoint Inhibitors (ICI) Therapy for previously-untreatable/refractory diseases
- Define T-cell exhaustion, immune checkpoint and immune checkpoint inhibitors (ICI).
- Explain regulatory PD-1 and CTL4 signal pathways that induce T-cell exhaustion during anti-cancer response or persistent infections (HIV/HBV/HCV).
- Discuss ICI blockade mechanisms whereby FDA-approved ICI treatments restore exhausted T cell effector function leading to anti-cancer immunity or pathogens clearance.
- Explain why advanced cancers can be effectively treated with ICI anti-PD-1/PDL-1 and anti-CTLA4 blockade therapies and describe how ICI treatments can enhance neoadjuvant therapy for cancers.
- Describe how ICI therapy has provided lasting remission and even cures for a subset of patients with specific cancers.
- Describe promising observations that ICI therapy shifts treatments for early-stage cancers, significantly increasing cancer-free outcomes.
- Describe side effects of ICI therapy and discuss managing principles.
Topic #2A: Unconventional T cells (γδ T/ MAIT/ NKT) versus conventional T cells (CD4/CD8) in immunity and therapeutics
- Compare unconventional γδ T/MAIT/ NKT cells and conventional CD4/CD8 T cells in terms of T cell receptor types, peptide vs non-peptide antigens(Ag) and associated Ag-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.
- Understand observations that unconventional T cell populations play roles in homeostasis and immune responses/immunity.
- Understand the immunity prototype in which non-peptide phosphoantigen-specific γδ T cells contribute to fast-acting (innate-like) mucosal immunity to tuberculosis infections.
- Describe the observation that γδ T cells in the tumor-infiltration lymphocytes (TIL) are a top favorable predictor of tumor outcome, and understand fundamentals for allogeneic γδ T cell transfer therapy against cancers.
Topics #2B-#2D: The revolutionary T-cell Transfer Therapies, approved by FDA, can treat or cure refractory or untreatable cancers and autoimmune diseases (Topic #2B address TIL therapy; Topics #2C-#2D engage CAR T cell therapy).
- Define TIL therapy and chimeric antigen receptor (CAR) T cell therapy in T-cell transfer immunotherapeutics.
- Describe similarity and difference in manufacturing procedures between TIL and CAR T cell therapies for autologous adoptive transfer (infusion) treatments.
- Compare immune mechanisms whereby TIL and CAR T cells can recognize and attack cancer cells or diseased cells.
- Understand why infused CAR T cells can proliferate/exist in the patients for longer time than TIL cells from CAR molecular signaling standpoints.
- Describe principle and steps of CD19-directed CAR T cell therapy against blood cancers.
- Describe how TIL and CAR T cell therapies can provide game-changing treatments of refractory or untreatable cancers.
- Understand why TIL and CAR T cell therapies have different applications for solid tumors and blood cancers.
- Discuss why CAR T cell therapy can serve as living drug for blood cancers, with long-term remission or cure in some subsets of cancer patients.
- Understand how evolving CAR T cell therapy can also treat solid tumors.
- Describe two major monitoring aspects after patients receive CAR T cell therapy.
- Understand why CAR T cell therapy is evolving to treat other diseases beyond cancers, including autoimmune diseases or even HIV/AIDS.
- Describe how CAR T cell therapeutics induce remission for refractory autoimmune diseases.
- Explain different treatment outcomes of CAR T cell transfer therapy in patients.
- Explain why CD19 CAR T cell therapy may induce cytokine release syndrome and long-term toxicities such as cytopenias and hypogammaglobulinaemia.
- Understand how ongoing immune innovations can improve CAR T cell therapy efficacy.
Topic #3: Trained immunity-based vaccines in broad-spectrum disease prevention; Topic #4 Cytokine signals targeted as immune interventions in treatments of refractory diseases.
- Define trained immunity.
- Discuss innate-immune-cell heterologous “memory” protection(trained immunity) in contrast with classical vaccine memory immunity.
- Understand mechanisms whereby live-attenuated vaccines/infections confer broad trained immunity against infections/diseases in pediatrics and adults.
- Describe a FDA-approved therapeutic vaccine (BCG) and its mechanism against blader cancer.
- Discuss a FDA-approved engineered cytokine that facilitates cure of refractory hepatitis C infection and understand the mechanism of cytokine signaling.
- Describe FDA-approved cytokines-targeted immune interventions in treatments of refractory autoimmune diseases such as rheumatoid arthritis.
Topic #5: Nanobiotech-innovated medicines in immunity/therapeutics; Topic #6: Engineered monoclonal antibodies (mAb) including bispecific Ab in immunity and therapeutics
- Understand and discuss biomedical aspects of nanobiotechnology, particularly the nano-formulation and nano-drug delivery to targeted cells in immunity and therapeutics.
- Describe prototypes of nanobiotech-innovated products approved by the FDA for disease prevention and therapeutics.
- Discuss a prototype of FDA-approved engineered monoclonal mAb in present and evolving prevention and therapeutics.
- Describe immune mechanisms whereby engineered mAb work against diseases.
- Discuss common side effects and managing principles of nanotech-innovated medicine and mAb-based products.
Topic #7: Host factor-targeted Gene Therapies and Stem Cell Therapies for Disease Remission/Cure/Prevention
- Understand FDA approved 1st Gene Therapy for Bladder Cancer, and complete clinical response in a subset of patients.
- Understand 1st FDA-approved CRISPR Cas9-based gene therapy and mechanism of action for the representative genetic disease (sickle cell disease).
- Discuss host-pathogen interaction in the context of HIV and host genetic factors for the ‘HIV cure’ potential.
- Discuss combined Gene and Stem-cell therapies against HIV/AIDS control or cure potential.
COMPETENCIES:
At the end of this experience the student should be able to:
- Apply immunological & biomedical principles to evidence-based medicine.
- Gain and consolidate skills/capabilities for in-depth learning and for presenting and evaluating publications/data through paper discussions and topics engagements.
- Understand precision medicine and 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.
INSTRUCTIONAL FEATURE:
The course “Immunological & Biomedical Successes of Treating/Curing Refractory/Untreatable Diseases” is a Zoom-online only course. The two-week course will have multiple topics, and each topic includes two days of modules/activities (note a different time for Topic #2A and Topic #7): Day-one modules entail group-based in-depth learning activities in which all groups will watch short PPT presentation video(s) from the NIH-funded experts; each group will read/discuss topic-specific paper(s)/theme questions while developing short PPT (<15 slides) presenting background/rationale/major findings/conclusive points 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) from immunological, biomedical and clinical standpoints.
Students will be randomly divided into multiple groups based on the registered number. Since there will be 7 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 for presentation/sharing next day. Each of the students (except presenters) will be asked to write a half-page essay or bullet points summarizing major findings for the assigned paper(s). Faculty will be involved daily, and 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.
Through paper discussions and topics engagements, students are able to gain/consolidate skills/capabilities for immunological/biomedical learning and for presenting/evaluating publications/data. These skills/capabilities will facilitate students clinical/academic career development.
ASSESSMENT:
This is a Satisfactory/Unsatisfactory course. In order to pass the course, students must complete all assigned online modules and 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 (<15 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. Students need to submit short essays or summarizing points to faculty. 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. The faculty will provide feedback comments to students. Students may submit completion certificates for any online modules where one exists.
Administrative Information Heading link
-
Program Number
ELEC 537
-
Program Contacts
Program Director: Zheng Chen, MD, PhD
Email: zchen@uic.edu -
Program Information
Duration: 2 Weeks
Night Call: No
Weekends: No
Students Accepted: Min. 3; Max. 35
Lectures/Conferences/Faculty hours per week: Approximately 12-18 hours per week
Laboratory hours per week: none
Independent Study hours per week: up to 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