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Cancer patients are at increased risk for a severe course of Covid-19 after SARS-CoV-2 infection. A recent study conducted by the Clinical Cooperation Unit Translational Immunology and the Department of Immunology at the University Hospital of Tübingen as well as the Robert Bosch Center for Tumor Diseases in Stuttgart uncovered a reduced SARS-CoV-2 T cell response as underlying reason for the dismal outcome in cancer patients. The research team developed a multi-peptide vaccine candidate for the induction of SARS-CoV-2-specific T cell immunity in cancer patients. The results of the study were recently published in Cancer Discovery, a journal of the American Association for Cancer Research.
Cancer patients, in particular patients with hematological malignancies such as leukemias or lymphomas, are at increased risk of a more severe disease course after SARS-CoV-2 infection. A compromised immune response in tumor patients due to the disease itself and/or caused by cancer therapy may constitute the reason for the dismal outcome. "After infection with SARS-CoV-2, but also after prophylactic vaccination the formation of a specific immune response, is essential for protection against COVID-19 disease and the development of long-term immunity," explains Dr. Juliane Walz. Two components of the immune system play a crucial role in the development of immunity: B cells form antibodies that can neutralize the virus, whereas T cells destroy virus-infected cells and support the formation of antibodies. Dr. Walz's research group has studied the immune response against SARS-CoV-2 in tumor patients. The reported data provides important insights into pathophysiology, but also for the prediction of COVID-19 disease severity and enables the development of therapeutic interventions and vaccines for this vulnerable patient group.
The study that was funded by the German Federal Ministry of Education and Research included cancer patients during and after SARS-CoV-2 infection. Immune responses against the virus were compared to those of individuals without cancer diagnosis. "We found that the antibody response against SARS-CoV-2 in tumor patients was comparable to that of non-cancer Covid-19 convalescents. In contrast, tumor patients – and in particular patients with hematological malignancies – showed significantly reduced T cell responses against SARS-CoV-2. Furthermore, T cells from tumor patients recognized fewer different components of the coronavirus. This so-called reduced diversity of the T cell response in tumor patients was associated with a severe course of COVID-19 disease," Dr. Walz said.
In addition, the study that was conducted in collaboration with the Departments of Hematology and Oncology in Tübingen and Bonn, as well as the Tübingen Clinic for Gynecology, Dermatology and the Department of Urology, examined blood samples from cancer patients obtained before the outbreak of the pandemic and thus without any contact to SARS-CoV-2. In a previous study, the researchers from Tübingen, had demonstrated that so-called cross-reactive T cells against SARS-CoV-2 are present in up to 81 percent of healthy donors due to prior contact with other common cold coronaviruses. Such preexisting cross-reactive T-cell responses may provide protection against SARS-CoV-2 and COVID-19 disease. The Tübingen research group has now been able to demonstrate that such cross-reactive T cell responses are significantly reduced in patients with leukemias and lymphomas. As underlying reason, a general exhaustion of the T cell immunity in these patients was identified, which is exemplified by a likewise reduced T cell response against other viral diseases.
Based on the findings of this study, the CCU Translational Immunology team (Medical Director: Prof. Dr. Helmut Salih) together with the Department of Immunology (Director: Prof. Dr. Hans-Georg Rammensee) in Tübingen is preparing a clinical trial to investigate a SARS-CoV-2 vaccine for specific induction of SARS-CoV-2-specific T cell immunity cancer patients. The vaccine candidate termed CoVac-1 has already been evaluated in a trial that enrolled healthy volunteers. Preliminary results show induction of strong T-cell responses after vaccination.
Universitätsklinikum Tübingen
Medizinische Klinik
KKE Translationale Immunologie
PD Dr. Juliane Walz
Otfried-Müller-Straße 10, 72076 Tübingen
Tel. 07071 29-88548
presse@med.uni-tuebingen.de
Pre-existing and post-COVID-19 immune responses to SARS-CoV-2 in cancer patients; https://cancerdiscovery.aacrjournals.org/content/early/2021/05/14/2159-8290.CD-2...
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