Williams Cancer Institute

Intra-Tumoral Injection: Unleashing the Power of Immune Response

Intra-Tumoral Injection: Unleashing the Power of Immune Response

The immune system produces proteins, known as chemokines, which are signals that can affect immune function.  There is a chemokine named C-C motif ligand 20, also known as CCL20.  It is known as an inflammatory protein, often associated with rheumatoid arthritis.  However, new evidence links this cytokine with numerous cancers.  It seems that CCL20 promotes cancer metastasis.  In addition, it increases cancer stem cells and causes T cell exhaustion.  These actions will suppress an immune response.  There are studies in many cancer types indicating that blocking CCL20 is anti-cancer and may enhance the success of immunotherapy.  Surprisingly enough, drugs that can block CCL20 may also reduce autoimmune side-effects from standard PD-1 immunotherapy, such as Opdivo and Keytruda.  Unfortunately, patients with autoimmune side effects are typically given steroids to treat these issues, which can reduce the success of immunotherapy. It seems these arthritis medications would be a better choice because they reduce side effects and increase immunotherapy success.  They appear on their own to be cancer immunotherapy.

So what drugs arthritis am I discussing?  I am talking about three FDA-approved medications, Infliximab, Tocilizumab, and Etanercept.  These drugs all indirectly block CCL20.   Though more studies are needed, it seems using any of these with immunotherapy can increase response rates while possibly lowering autoimmune side effects.  I am sure the potential benefits will lead to new drugs specifically designed to inhibit the CCL20-CCR6 axis.   Also, some natural agents have inhibition of CCL20, including Epigallocatechin gallate (EGCG) and gallotannin.    These arthritis drugs are a reasonable consideration that can be deployed right away since they already have approval for a different purpose. Indeed they may have great value in patients who have failed or developed autoimmune side effects from standard immunotherapy, such as Opdivo and Keytruda.

Reference: Jason R. Williams, 15 Oct 2019, The Immunotherapy Revolution: The Best New Hope For Saving Cancer Patients’ Lives, https://williamscancerinstitute.com/the-immunotherapy-revolution

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