A new type of immunotherapy for the skin cancer malignant melanoma shows promising results. Three severely ill patients are now long-term survivors. The study, published in OncoImmunology, is the result of a collaboration between researchers at Karolinska Institutet and Karolinska University Hospital.

“Immunotherapy is based on activation of the body's own immune defence to eliminate cancer cells. Immunotherapy achieved substantial progress, particularly when the treatment with immune-activating antibodies (Immune Checkpoint Inhibition, ICI) was introduced. This prolongs the survival of patients with advanced melanoma,” says Maria Wolodarski, oncologist and researcher at Karolinska Institutet, who is the study's principal investigator and responsible for patient contact and recruitment.

James Allison and Tasuko Honjo were awarded the Nobel Prize in Medicine two years ago for the discovery which resulted in ICI treatment.

New Immunotherapy combination method

However, the majority of patients with advanced malignant melanoma do not respond to this or other types of treatment. It is this group that the research team has now treated with a new combination of two types of immunotherapy.

First, a special type of white blood cells, T-cells, is extracted from the patient's own tumour. Those “Tumour Infiltrating Lymphocytes”, TIL cells, are an important part of the body's immune defence against cancer. The TIL are multiplied up to 50 billion cells and administered back to the patient in combination with a growth factor, Interleukin-2.

“What makes this study unique compared to other international clinical trials with TIL cells is that the patients are also treated with several doses of a tumour vaccine consisting of dendritic cells, DC, which specialise in activating the immune system and giving the injected TIL cells an extra boost,” says Stina Wickström, researcher at the Department of Oncology-Pathology at Karolinska Institutet, and responsible for coordinating production of the TIL cells and for the study's immune monitoring.

Other types of metastatic cancer

Of the four severely ill patients with malignant melanoma receiving treatment with this combination of TIL cells and DC tumour vaccine, three have responded with complete or near complete remission of the cancer. This has occurred in spite of the fact that the group no longer responds to other types of cancer treatment. They are long-term survivors who have had the disease for several years.

The five patients that have been treated with TIL cells alone did not have the same favourable response to the treatment as when the treatment was provided in combination with the tumour vaccine.

The method is part of Karolinska University Hospital's strengthening of cell therapy and Rolf Kiessling, head of the study, has applied to the Swedish Medical Products Agency for approval to also test the method on other types of metastatic cancer.

This investigator-initiated study is financed by the Swedish Cancer Society, the Cancer Society in Stockholm, the Swedish Research Council, the City of Stockholm, Knut and Alice Wallenberg Foundation, Torsten Söderberg Foundation, Vinnova, the Swedish Foundation for Strategic Research and GE Healthcare.

Last author Rolf Kiessling is the chairman of the board/consultant for Clinical Laser Thermia Systems, research consultant for Anocca AB and Phion Pharmaceuticalics and receives research grants from those companies. Roger Tell is employed by Isofol Medical. John Hansson has been the principal investigator for testing financed by AstraZeneca, Bristol Myers-Squibb, Merck, Novartis, Roche and Clinical Laser Thermia Systems, and has been awarded research grants from Bristol Myers-Squibb and Merck. Tanja Lövgren has received lecture fees from Bristol Myers-Squibb.

Publication

“Complete and long-lasting clinical responses in immune checkpoint inhibitor-resistant, metastasized melanoma treated with adoptive T cell transfer combined with DC vaccination”. Tanja Lövgren, Maria Wolodarski, Stina Wickström, Ulrika Edbäck, Mette Wallin, Eva Martell, Katrin Markland, Pontus Blomberg, Maria Nyström, Andreas Lundqvist, Hans Jacobsson, Gustav Ullenhag, Per Ljungman, Johan Hansson, Giuseppe Masucci, Roger Tell, Isabel Poschke, Lars Adamson, Jonas Mattsson, and Rolf Kiessling. OncoImmunology, online 11 July 2020, doi: 10.1080/2162402X.2020.1792058.