Stina Wickström

Every year around 1200 females are diagnosed with either ovarian or cervical cancer in Sweden. When relapse occur, the response rate to the second line of therapy is very low and no cell-therapies are available.  I have extensive knowledge regarding ACT, both form our clinical trial MAT02 focusing on tumor infiltrating lymphocytes (TIL) to treat melanoma patients as well as generation of tumor specific T cell from the blood using in silico predicted neoantigens loaded on dendritic cells (DC).  Based on this knowledge, we will further develop a TIL expansion protocol to improve the efficacy of TIL, to increase autologous TIL-Tumor recognition and investigate if it is possible to generate an ACT product from blood using neoantigen loaded DC from these patients. Furthermore, we will use a novel method using an FDA approved drug to preserve the antitumor capacity of the cytotoxic cells used for ATC during oxidative stress. Combining this novel finding with our clinical protocols will further improve the ACT product. Lastly, for melanoma, we have observed that TIL-Tumor recognition can be influenced by if tumor cells are grown in 2D vs 3D models due to immunoproteasome upregulation. Therefore, we will analyses the efficacy of the new cell products using 3D models to investigate if similar results can be observed when analyzing cells form gynecological tumors.  When we succeed, we have the opportunity to treat patients with personalized cell-based therapy.

Each year, a total of approximately 1,200 women are diagnosed with ovarian or cervical cancer in Sweden. Oxidative stress, ROS, has been shown to be a contributing factor to the onset of these cancers. Chronic inflammation caused by, for example, viral infections leads to the activation of regulatory cells, MDSCs, which produce high levels of ROS. High levels of ROS can cause genetic damage and greatly reduced function of the body's "killer cells". Today, unfortunately, there is no treatment that has been proven to make a difference for patients with recurrent disease. Cell therapy involves reactivating the individual's killer cells so that they can eliminate the cancer cells. Our research is based on immunotherapy and more specifically on adoptive cell therapy (ACT). ACT means that you "take out" the patient's own immune cells, either killer cells or dendritic cells (DC), activate them and then give them back to the patient as cell therapy or DC vaccine. DCs are specialized in activating killer cells to respond to changes found only on cancer cells so that the killer cells eliminate the tumor. We have previously created a treatment where we combine activation of killer cells from the patient's own tumor with a DC vaccine. This has shown promising results as a treatment for patients with severe skin cancer. The goal is to be able to expand this treatment method, combine killer cells from the patient's tumor with an active DC vaccine and to develop a new method where we activate the patient's killer cells from the blood via DC cells loaded with tumor-specific changes, as new treatment strategies for patients with recurrent gynecological cancer. We also want to equip the killer cells so that they become more tolerant to ROS before they are given back to the patient in order to preserve the ability of the killer cells to eliminate the cancer cells despite high levels of ROS in the tumor. When we succeed, we can provide a meaningful treatment through this type of tailored immunotherapy.