Most lymphomas and leukemias are neo¬plasms of B cells. Due to the many different B cell development stages from which these neoplasms arise, the resulting diseases are quite heterogeneous, which... Show moreMost lymphomas and leukemias are neo¬plasms of B cells. Due to the many different B cell development stages from which these neoplasms arise, the resulting diseases are quite heterogeneous, which amongst other things is manifested in different tumor growth location, proliferation potential and surface antigen repertoire. Neverthe¬less, some population characteristics are found in almost all B cell malignancies as the cell-of-origin is identical. One of these is the cell surface antigen CD20. Originally used as a marker to distinguishing B cells from other lymphocytes, it quickly became a target for immunotherapy. Immuno-therapy is a treatment that makes use of immune system components to fight cancer, in this case by the injection of a monoclonal antibody specifically targeting one protein: CD20. The addition of CD20-targeting an¬tibodies to an anti-tumor treatment allows your immune system to recognize CD20-ex¬pressing B cells (diseased and healthy), and dispose of them. Overall, after several decades of research and therapeutic experience with antibodies targeting CD20, new functional discoveries as well as therapeutic advances are still being made, and CD20 therefore remains a highly attractive and fruitful target for the therapy of B cell malignancies as well as certain B-cell mediated autoimmune diseases. Show less
This thesis focused on different aspects of melanoma treatment with immunotherapy and targeted therapy. In chapter 2 we search for biomarkers that could be associated with overall survival in... Show moreThis thesis focused on different aspects of melanoma treatment with immunotherapy and targeted therapy. In chapter 2 we search for biomarkers that could be associated with overall survival in patients treated with ipilimumab. In chapter 3 we describe diarrea, a commonly seen side effect of immunotherapy. Here we show that there is no significant correlation between grade of diarrhea and severity of colitis as seen during endoscopy. Chapters 4 and 5 describe patients with brain metastases and/or leptomeningeal metastases. In chapter 4 we show the difference in overall survival in patients treated with vemurafenib, dabrafenib or the combination of dabrafenib + trametinib. Chapter 5 focusses on the treatment of leptomeningeal metastases. Here a significant difference in overall survival was noted between treated and untreated patients. Furthermore LDH was a predictive biomarker for overall survival. In chapter 6 we show that treating patients with vemurafenib beyond progression of disease has a significant impact on overall survival. Lastly in chapter 7 we review the past, present and future of treating patients with different kinds of cancer with tumor-infiltrating lymphocytes. Show less
The breakthrough of immunotherapy for cancer has introduced promising new options, but nonetheless only a minority of cancer patients show significant clinical benefit. This situation has inspired... Show moreThe breakthrough of immunotherapy for cancer has introduced promising new options, but nonetheless only a minority of cancer patients show significant clinical benefit. This situation has inspired two avenues of research to find solutions to this problem: mechanistic studies to decipher the working mechanisms of immunotherapies and to investigate why many patients do not respond, and studies developing combination treatments to achieve clinical benefit in situations where immunotherapy alone is not sufficient. This thesis explores both these avenues by investigating applications of visible light in immunotherapy of cancer in pre-clinical models. We developed optical imaging platforms for visualization of immune cells and immunotherapies, which can shed light on the immunological events after administration of immunotherapy. In addition, we investigated novel therapies based on the combination of tumor ablation by Photodynamic Therapy and different types of immunotherapy. Our findings may prove useful in understanding success and failure of immunotherapy, and provide new combination treatment options when the efficacy of monotherapy is insufficient. Show less
The generally poor prognosis of patients with epithelial ovarian cancer patients treated with curative intent, calls for additional treatment modalities and possible success might lie in a... Show moreThe generally poor prognosis of patients with epithelial ovarian cancer patients treated with curative intent, calls for additional treatment modalities and possible success might lie in a combination of chemotherapy and immunotherapy. This thesis focuses on the interaction of chemotherapy with the immune system and describes new combined chemo-immunotherapy treatment strategies. This thesis has explored new strategies, immune-modulation of the IL-6 pathway and a vaccine against p53, to enhance immune surveillance and to disable tumour immune evasion in ovarian cancer patients. The future challenge for immunotherapy against ovarian cancer is a tailored combinatorial approach to test the rationale of potentially synergistic therapies that can induce efficient antitumour immunity and prolong patients’ survival. Show less
Trautinger, F.; Eder, J.; Assaf, C.; Bagot, M.; Cozzio, A.; Dummer, R.; ... ; Knobler, R. 2017
Conventional therapies as chemotherapy and radiotherapy impact immune populations and immune responses in cervical cancer patients. This led to new perspectives into the important role of the... Show moreConventional therapies as chemotherapy and radiotherapy impact immune populations and immune responses in cervical cancer patients. This led to new perspectives into the important role of the immune system and possibilities to optimally implement immunotherapy in the treatment of cervical cancer. Immunotherapy with HPV16-SLP vaccination is a suitable candidate for combined therapy with chemotherapy, when administered within the optimal time window, as it maximizes vaccination efficacy while tumor-induces immune suppression is tackled. To eventually improve clinical outcome in cervical cancer patients, multimodality treatment approaches need further exploration. Within that approach, the assignment of treatment dose, timing and route of administration of both immunotherapy and the classic conventional therapies are important. In addition, individualization of patients therapy based on immune markers prior to treatment should be a goal to optimize combination therapy, minimize side effects and improve clinical outcomes. Show less