Functional Genome Profiling to Understand Cancer Immune Responsiveness

Ena Wang1, Davide Bedognetti2, Francesco M Marincola3

  • 1Allogene Therapeutics, South San Francisco, CA, USA. ewang911@gmail.com.

Insights

Minimally invasive serial biopsies reveal cancer immune responsiveness (CIR) predictors and therapeutic mechanisms. This approach, studying CIR in situ, has advanced immune oncology (IO) research over two decades.

Area of Science:

  • Oncology
  • Immunology
  • Genomics

Background:

  • Minimally invasive serial biopsies were proposed nearly two decades ago to study cancer immune responsiveness (CIR).
  • Early work identified CIR predictors, characterized therapeutic pharmacodynamics, and elucidated immune escape mechanisms.
  • Subsequent research has validated and refined these initial findings.

Purpose of the Study:

  • To summarize the historical application of functional genomic profiling in immune oncology (IO).
  • To highlight the role of serial biopsies in understanding CIR, therapeutic MOA, and immune escape.
  • To present new insights from emerging single-cell technologies.

Main Methods:

  • Utilizing minimally invasive serial biopsies to analyze CIR directly within the tumor microenvironment.
  • Employing functional genomic profiling to identify response predictors and mechanisms of action.
  • Integrating data from multiple biopsies over time to track dynamic biological changes.

Main Results:

  • Established early predictors of CIR in 2002.
  • Characterized the pharmacodynamics of various immune therapeutics.
  • Documented tumor cell strategies for immune escape under treatment pressure.

Conclusions:

  • Minimally invasive serial biopsies are a powerful tool for dissecting cancer immunology.
  • Functional genomic profiling has been crucial for discovery and validation in IO.
  • Novel technologies promise further advancements in understanding and treating cancer immunity.

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