Engineered Cellular Therapies Enter Treatment Landscape of Melanoma

Bruce L. Levine, PhD

While chimeric antigen receptor (CAR) T-cell therapies have been particularly promising in hematologic malignancies, engineered anticancer immunity with T-cell and natural killer (NK)-cell therapies provide further hope in the treatment landscape of melanoma, according to a presentation at 16th Annual International Symposium on Melanoma and Other Cutaneous Malignancies®.

Preclinical trials are ongoing to demonstrate the potential abilities of cellular therapy in melanoma, but these trials are still in the early stages. More research needs to be done to further develop these therapies, but they have already gained a lot of interest following the successes observed in hematologic malignancies, such as lymphomas and leukemias.

Research remains ongoing for the use of CAR T- and NK-cell therapies as treatment of patients with melanoma and other solid tumors. As this continues, Bruce L. Levine, PhD, expects to see the clinical utility of this therapy expand in the melanoma space.

“It is also important to recognize the patients who participate in our clinical trials. Without them volunteering to participate in our clinical trials, we are unable to make advancements in new therapies,” said Levine.

In an interview with Targeted Oncology, Levine, Barbara and Edward Netter professor in Cancer Gene Therapy at the University of Pennsylvania Perelman School of Medicine, discussed hot topics in the treatment landscape of melanoma, including the development of CAR T and NK cells.

TARGETED ONCOLOGY: Could you provide an overview of the hot topics in melanoma?

Levine: I spoke [at the International Symposium on Melanoma] in the Hot Topics session about engineering immunity through genetic modification of T cells to redirect specificity against cancer antigens. We have started off in this field with great success in hematologic malignancies targeting CD19 in pediatric acute lymphoid leukemia and in diffuse large B-cell lymphoma. Solid tumors have proven more challenging, in part due to targets and the fact that solid tumors tend to be more immunosuppressive. They are also more difficult to access, so when one thinks about leukemia accessible from all angles, it is a single angle cell suspension; solid tumors have to be attacked without or through vascular access, which at times, is poor.

TARGETED ONCOLOGY: What would you say is the key takeaway?

Levine: The key takeaway from this field of engineered anticancer immunity using T cells and NK cells is we are still at the very early stages. We are at the equivalent of the model T stage. There will be modifications and improvements being made, so we should not despair that we are not seeing activity in solid tumors currently. I expect that will happen with improvements to T cell and NK cell engineering, as well as the discovery of new tumor antigens and combinations with other modalities, including vaccines, oncolytic viruses, checkpoint antibodies, and additional therapies.

TARGETED ONCOLOGY: Are there any preclinical trials of CAR T cells that are ongoing?

Levine: There are many CAR T-cell clinical trials around the world. Some count more than 350 trials. The majority of these are in the hematologic malignancies, including leukemias, lymphomas, and myeloma. However, there are more and more targets in solid cancers, including melanoma, but we are at the very early stages in solid tumors. I expect with the explosion of interest and funding coming into the field that we will see more clinical results in the coming years.

TARGETED ONCOLOGY: Is there anything underway at your organization to further advance the treatment landscape for melanoma with CAR T cells?

Levine: At my institution, we have a very active program in melanoma. BRAF inhibitors and other agents, such as vaccines and engineered anti-melanoma T cells, so we are optimistic. However, we are looking at combining all of these modalities with checkpoint antibody therapy and improvements with the technologies to advance the field.

TARGETED ONCOLOGY: What did you enjoy most from this meeting?

Levine: I looked forward to hearing from the participants and their questions of the speakers to understand what we have to do in communicating advancements in the field. I also like hearing from people in allied fields as it often integrates knowledge. We gain ideas from hearing from those who are not directly in the field.

TARGETED ONCOLOGY: Is there a message you would like to share in regard to the advancements in melanoma?

Levine: It is also important to recognize the patients who participate in our clinical trials. Without them volunteering to participate in our clinical trials, we are unable to make advancements in new therapies.