Topline Presentation Points 

CAR cell therapy
Today
  • CAR-T cell therapy is now established as standard of care for a small subset of hematological malignancies. While the majority of these therapies are directed against B-cell markers, clinical trials are underway to investigate the efficacy of this technology in other indications both in hematological and solid tumours
(Near) future
  • A major drawback to T-cell based techniques is the requirement to ship cells to central processing sites for engineering which is both costly and time consuming
  • New cell subtypes are being integrated into CAR platforms to create “off-the-shelf” products
Challenges/considerations
  • Patients can relapse on CAR-based therapies due to downregulation or loss of antigen binding sites on the tumour that the therapy is targeted to
  • There are early phase trials looking at bispecific CAR-T therapies (e.g. CD19/CD22, CD19/CD20) to see if they can overcome this issue
  • Other mechanisms of CAR-T failure need to be addressed including methods to increase in vivo persistence and strategies to mitigate the action of inhibitory factors from the microenvironment
  • Still in the process of identifying characteristic that are associated with CAR-T efficacy, failure and toxicity
CRISPR/Cas9 gene editing is capable of revolutionizing medicine as we know it
Today
  • Gene editing with CRISPR/Cas9 technology is emerging in benign and malignant hematology. Disorders being investigated include sickle-cell disease, beta-thalassemia, and hemophilia
  • CRISPR technology is also being used to remove checkpoint inhibitors in T-cells to improve efficacy
(Near) future
  • CRISPR/Cas9 may be used to genetically modify cell therapies to render them unresponsive to inhibitory factors emanating from the tumour microenvironment (e.g. checkpoint proteins, TGFbeta, etc.) that may antagonize their anti-tumour activity. These alterations are designed to improve their efficacy in context of the tumour microenvironment
Challenges/considerations
  • Specificity: making sure “edits” only take place at the desired location in the genome
  • Development of technology to assess and reduce potential off-target effects
  • Additional infrastructure will be required to govern implementation
Immunotherapy – Checkpoint Inhibitor
Today
  • New checkpoints inhibitors are being developed that target axes other than PD-1/PD-L1
(Near) future
  • Of note TIM-3 and TIGIT are being investigated as a target for many early phase drugs
  • Similarly, new biomarkers are being identified and targeted with antibodies and BiTEs
Challenges/considerations
  • One of the major factors affecting the efficacy of immunotherapies is the tumour microenvironment (TME)
  • Identification of novel molecules that overcome the inherent inhibitory nature of the microenvironment represents a much-needed avenue to maximize the potential of immunotherapies
Microbiome and the Immune System
Today
  • There is a greater appreciation for the gut microbiota’s role in immune regulation, both in normal homeostasis and cancer
  • Early research suggests the commensal bacteria and the microbial-derived metabolites may impact the efficacy of ICIs
Future
  • Research is being pursued to gain a deeper understanding of the mechanisms of microbiota-mediated immunomodulation
  • Areas of interest include the identification of microbial biomarkers that predict response to immunotherapy in addition to the development of therapies targeting microbial-factors