Looking Ahead for Melanoma Treatment

While checkpoint inhibitors are a mainstay in the field of advanced melanoma treatment, novel and reimagined therapies offer new hope for this challenging disease state. These therapies include using older agents like interluekin-2 (IL-2) or tumor-infiltrating lymphocytes (TILs) and modifying them to make their activity more potent against melanoma. Additionally, oncolytic vaccines administered into the tumor or systemically can help to sensitize the immune system and improve the response to checkpoint inhibitors.

Here, Jose Lutzky, MD, skin cancer physician at the Sylvester Comprehensive Cancer Center at the University of Miami, discusses the ongoing research in this field.

0:05 | We have a pretty robust clinical research program for melanoma. We have a couple of trials in which we are modifying the T cells to be more targeted. And 1 of the problems with this approach is that when we do that, patients have to have a specific type of immune system or so-called HLA type. And, and sometimes, you know, the the HLA type that we target, it reaches only sometimes 40 to 50% of the population. We're doing other trials now that are targeting other HLA types to try to offer this to more people. We're also doing trials with modified cytokines.

0:58 | So interleukin-2 when used by itself, actually has a response rate of about 10% in metastatic melanoma, and about 6% of the patients have a complete response, and the tumor never comes back. And it was used in the past a lot because of that 6% response. But as I mentioned, it's a very toxic drug. So when checkpoint inhibitors came along we stopped using interleukin-2. Now, the reason why only 6% or 10% respond is that because interleukin-2, has this yin and yang. It helps kill the tumor cell, but also increases some of these inhibitory cells, particularly a group of cells called T-regs.

1:47 | Scientists have defined which receptors to what, in terms of the good effects and the bad effects. And there are now a number of studies out there that modify interleukin-2 molecule to only do the good things and less of the bad things. That particular study that we're using has an antibody attached to the IL-2 molecule that brings that IL-2 only to the CD8 cells, which are the lymphocytes, that are really the soldiers of the immune system and go after the tumors.

2:27 | And so that approach has had has had less toxicity, and patients don't need to be in a hospital for that. And we already have seen some responses. So that's 1 approach. And you know, we we have a number of oncolytic, viral vaccines, which are either given directly into the tumor or into the bloodstream. And in these approaches, the idea there is to sensitize tumors that are not responding to immunotherapy. There are so called cold tumors, which means they do not allow the immune cells to infiltrate the tumor.