Intralesional IL-2 combined with anti-PD-1 for melanoma - and links to additional intel on intralesional/intratumoral therapies

From the moment I started seeing research about them, I've been a big fan of intralesional therapy ~  drugs injected directly into accessible melanoma tumors.  My Primer for Melanoma Treatment  contains a link that covers a great deal of what is known about them.  As I note there,

Intralesional drugs include (but are not limited to):

CAVATAK - derived from the Coxsackievirus
T-VEC - also called OncoVEX, Imlygic,  or Talimogene Laherparepvec - uses the herpes virus with GM-CSF
PV-10 - derived from Rose Bengal
HF10 - also derived from HSV
SD101 - a TLR9 agonist
IL-2 -  is also being used

From earlier this year:  In-transit melanoma metastases and PV-10 vs isolated limb perfusion, an update...

There was this update in 2018:  Reports on Intralesionals for melanoma - T-VEC, SD-101, and Dendritic cells

Here are two more reports from 2018:  T-VEC in melanoma, after progression on immunotherapy and BRAFi with good results! 3 case reports... and In-transit melanoma. Two "new" treatment options!

And from this summer, there is this:

Successful combination therapy of systemic checkpoint inhibitors and intralesional interleukin-2 in patients with metastatic melanoma with primary therapeutic resistance to checkpoint inhibitors alone.  Rafei-Shamsabadi, Lehr, von Bubnoff, and Meiss.  Cancer Immunol Immunother. 2019 Aug 17.   

Systemic immunotherapy with PD-1 inhibitors is established in the treatment of metastatic melanoma. However, up to 60% of patients do not show long-term benefit from a PD-1 inhibitor monotherapy. Intralesional treatments with immunomodulatory agents such as the oncolytic herpes virus Talimogene Laherparepvec and interleukin-2 (IL-2) have been successfully used in patients with injectable metastases. Combination therapy of systemic and local immunotherapies is a promising treatment option in melanoma patients. We describe a case series of nine patients with metastatic melanoma and injectable lesions who developed progressive disease under a PD-1 inhibitor monotherapy. At the time of progressive disease, patients received intratumoral IL-2 treatment in addition to PD-1 inhibitor therapy. Three patients showed complete, three patients partial response and three patients progressive disease upon this combination therapy. IHC stainings were performed from metastases available at baseline (start of PD-1 inhibitor) and under combination therapy with IL-2. IHC results revealed a significant increase of CD4⁺ and CD8⁺ T cells and a higher PD-1 expression in the inflammatory infiltrate of the tumor microenvironment in metastases from patients with subsequent treatment response. All responding patients further showed a profound increase of the absolute eosinophil count (AEC) in the blood. Our case series supports the concept that patients with initial resistance to PD-1 inhibitor therapy and injectable lesions can profit from an additional intralesional IL-2 therapy which was well tolerated. Response to this therapy is accompanied by increase in AEC and a strong T cell-based inflammatory infiltrate.

These are drugs I would certainly try, especially in combination with immunotherapy, should I have the need.  For what it's worth. ~ c