Regulatory Science Symposium: Emerging Technologies/Treatments 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 


Accompanying text created by Yelin (David) Hu | Regulatory Science Student Worker |

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