Turning Up the “Temperature” in Tumors

WRITTEN BY

Koustubh Ranade, PhD VP, R&D Translational Medicine

Scientists at MedImmune, the global biologics research and development arm of AstraZeneca, have made it their charge to target and trigger tumors into producing an immune response – one that will eradicate cancer.

New data from MedImmune – to be presented at the upcoming Society for Immunology of Cancer (SITC) Annual Meeting – highlights our company’s innovative approach to strengthen the body’s natural immune response against tumors, enabling the immune system to recognize, respond and regain control.

Mission Possible: Effectively Target Tumors

MedImmune’s current mission: reveal cancer cells hidden in plain sight. The immune system can normally detect and destroy abnormal cells. However, in some solid tumors, the immune system cannot recognize the danger signals that would alert and trigger it, thus allowing these cancer cells to continue their growth unchecked.

MedImmune’s secret weapon: cutting-edge approaches to biological problems. Leveraging our expertise in immunology, our scientists are interrogating an investigational agent named MEDI9197 that triggers a danger signal to help activate the patient’s immune system to fight the hidden cancer cells.

In some solid tumors, dubbed cold tumors, there are no or very few activated immune cells. For this reason, the immune system cannot recognize danger signals and therefore cannot get rid of the tumor. Dendritic cells are the first immune cells to see a danger signal and alert the rest of the immune cells, but they remain silent within cold tumors. Inside these dendritic cells are TLR7/8 receptors that are usually activated by various danger signals, including pathogens like viruses and bacteria.

When MEDI9197 is injected directly into a tumor (also known as “intratumor injection”), it binds to TLR7 or TLR8 receptors and activates dendritic cells, which then start activating and calling in other immune cells, turning a cold tumor into a hot one. It is our hope that by turning cold tumors hot, MEDI9197 will enable the immune system to fight tumors that were present but previously unseen.

MEDI9197 will also be studied in combination with other drugs, e.g. anti-PDL1 (durvalumab) in the future. MedImmune has direct evidence showing that an array of immune cells, both adaptive and innate cells are being activated in humans upon treatment with MEDI9197.

In addition, we are disclosing new insights obtained from cutting-edge single cell RNA sequencing, into how CD8 cells – one of the key tumor-killers of the immune system – become exhausted and dysfunctional because of chronic activation.

Commitment: Our Early Oncology Pipeline & Beyond

This precision medicine approach is a prime example of MedImmune’s strategy in Immuno-Oncology (IO):

  • Identify the molecular mechanisms underlying different kinds of cancer, understand how cancer escapes the immune system and how the immune system in turn recognizes and kills cancer cells.
  • Develop medicines that exploit these escape pathways, and identify those patients most likely to benefit with the use of a predictive biomarker or companion diagnostic.
  • Investigate monotherapy and combination therapies to address each mechanism that cancer uses so that we can fully engage the immune system.

These focus areas all play a critical role in gaining insights to further our understanding of the immune landscape of tumors.

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