Emerging Technologies/Treatments Bootcamp Session 5: Immunotherapy Trials (2017)

In this series, we will discuss regulatory considerations for conducting clinical trials in the era of emerging technologies and treatments.


Course Syllabus/Topics

Immunotherapy is treatment to stimulate or restore the ability of the immune system to fight infection and disease

Immunotherapy for Cancer:

  • Surgery may not remove every cancer cell
  • Chemotherapy and radiation therapy kill indiscriminately
  • Cancer can recur after apparently successful treatment

Autologous vs Allogeneic:

  • From patient vs from donor
  • HLA type - risk of rejection or GVHD
  • Immunosuppressive therapy

Immunotherapies Being Investigated:

  • Biological response modifiers
  • Tumor infiltrating lymphocytes (TILS)
  • mAb Therapy
  • T cell therapy
  • Dendritic cell therapy
  • Viral therapy
  • Chimeric antigen receptor (CAR-T) T cell therapy
  • Checkpoint inhibitors

Trial Considerations for Immunotherapy:

  • Biological Response Modifiers
    • Large scale manufacturing
    • Readily support large trials
    • Cross-reactivity to endogenous protein the drug mimics
  • Monoclonal Antibodies
    • Specificity in binding
    • Various oncology purposes
    • Concern for loss of efficacy
  • Tumor Infiltrating Lymphocytes
    • Isolation and growing of T cells
    • Personalized therapy
    • Trial size will be smaller than traditional products
    • The matching of HLA between donor and recipient
    • Concern for TILs targeting antigen expressed on health tissue
  • T cell therapy
    • Individualized autologous therapy
  • DC Immunotherapies
    • ICT-107
    • DC cells are highly potent antigen presenting cells
    • DC therapy involve isolation of PBMCs, driving DC formation, activating and exposing DCs to tumor antigen(s), re-introducing them to the patient
    • Fragile autologous cell-based therapy
    • Single patient manufacturing
    • Extremely high cost for large trials
  • Viral-based Immunotherapies
    • Oncolytic viruses
    • Not an autologous product
    • Manufacturing is not individualized
    • Patient and healthcare workers administering the drug cannot be immunocompromised
    • Drug must be stored and shipped at -80°C to maintain viability
  • CAR-T Immunotherapies
    • Clone a chimeric antigen receptor into T cells
    • Allows CAR-T cells to recognized, bind and kill tumor cells
    • Single patient manufacturing
    • Slow dose escalation necessary due to toxicity potential (cytokine release syndrome)
  • Checkpoint Inhibitors:
    • mAbs that are designed to bind and interrupt action of immune system regulators
    • Allows the immune system to rest
    • PD-2; PD-L1; CTLA-4
    • Traditional biotech products allowing large scale manufacturing
    • Readily support large trials
    • Often used in combination with another type of therapy 

Acknowledgement

Accompanying text created by Yelin (David) Hu | Regulatory Science Student Worker | yelinhu@usc.edu


NIH Funding Acknowledgment: Important - All publications resulting from the utilization of SC CTSI resources are required to credit the SC CTSI grant by including the NIH funding acknowledgment and must comply with the NIH Public Access Policy.