The current project aims to expand this treatment to ovarian cancer patients." /> adoptive T cell therapy, metastasized ovarian cancer | Anticancer Fund

Adoptive T cell therapy based on Tumor Infiltrating Lymphocytes for stage IV ovarian cancer.

Info

Location: CCIT, Herlev Hospital, Denmark
Collaboration: Prof Dr Inge Marie Svane

 

Cancer immunotherapy is regarded an important step in cancer treatment. The leading journal Science calls it the 'Breakthrough of 2013’. This because it’s the patient’s own immune system that is being targeted, rather than the tumour. In fact, immunotherapy causes the natural immune system to be stimulated in a way that it starts attacking the tumour on its own.

 

T-cells
T-cells are part of the immune system. They attack anything that does not normally belong to the body and kill malignant cells in the event of a viral infection or a tumour. When the immune system identifies tumour cells, these specific T-cells are directed to the tumour. Once they have penetrated the tumour these T-cells are referred to as tumour-infiltrating lymphocytes (TIL).

Adoptive T-cell therapy is a treatment in which a patient’s T-cells are removed from the tumour, then expanded outside the body away from all negative regulating factors of the tumour environment, and subsequently injected into the same patient. As they are expanded outside the body, these new T-cells have not been suppressed by the tumor and are fully armed and activated allowing them to kill tumour cells.

Impressive results

In the United States impressive results have been achieved in melanoma patients treated with chemotherapy and subsequently with  adoptive T-cell therapy. This therapy comprised large quantities of TIL-cells (taken from the tumour) and IL-2 (a substance which stimulates the expansion of T-cells) cultivated outside of the body. The first comparable clinical trial in Europe has not yet been completed, but the results are comparable and promising.

TIL study

The aim of this TIL study for metastasized ovarian cancer is to extend the use of immunotherapy to patients with ovarian cancer. Therefore, the expansion of the T-cells outside the body will first be studied and optimised. When it does, the capacity of killing ovarian cancer cells will be examined extensively in a preclinical trial.

In the second stage (during a clinical trial) the adoptive T-cell therapy has been tested in a clinical setting involving patients with advanced ovarian cancer. In total 6 patients have been admitted and the safety, as well as the immune response has been examined. The preclinical trial, a first step towards the optimisation of TIL expansion, initiated in April 2014. The clinical trial enrollmentd ended Q4 of 2016.

Professional info

Location: CCIT, Herlev Hospital, Denmark
Collaboration: Prof Dr Inge Marie Svane

 

T-lymphocytes (also named T cells) are part of the immune system and are the responsible component for cell killing in case of a viral infection or neoplasm (tumor). If tumor cells are found by the immune system, T cells that will recognize the malignant cells become activated and migrate towards and inside the tumor. Once they arrive in the tumor, these T cells are referred to as ‘tumor infiltrating lymphocytes’ (TIL). 

Adoptive T cell therapy (ACT) refers to a treatment in which T cells are given to a patient as the active ingredient.  The T cells are derived from the tumor of the patient, making this treatment uniquely tailored for each patient.

In the USA, impressive results have been obtained in melanoma patients treated with lymphodepleting chemotherapy, followed by ACT with high numbers of ex vivo expanded autologous TIL and IL-2 (cytokine stimulating T cell expansion). The first clinical trial in the Centre for Cancer Immunotherapy (CCIT) in Denmark with this protocol is completed, and preliminary results are similar as obtained in the USA.

The current project aims to expand this treatment to ovarian cancer patients. Therefore, in first instance the ex vivo expansion of the TIL has been optimized and compliant with GMP (Good Manufacturing Practice) conditions. The TIL’s phenotype, functionality and ability to kill ovarian tumor cell lines and autologous tumor has been extensively characterized.

In the second part of the project, the TIL based ACT will be tested in a proof-of-concept clinical trial in patients with disseminated ovarian cancer. In total, 6 patients are enrolled and the safety, and immune response will be documented. The recruitment started in 2015 after optimizing TIL expansion and ended Q4 of 2016 (NCT02482090).