Journal Articles

MHC tetramer technology: Exploring T cell biology in health and disease

Major histocompatibility complex (MHC) tetramers stand as formidable tools within T cell biology, facilitating the exploration and comprehension of immune responses. These artificial molecules, comprising four bound MHC molecules, typically with a specified peptide and a fluorescent label, play a pivotal role in characterizing T cell subsets, monitoring clonal expansion, and unraveling T cell dynamics during responses to infections or immunotherapies. Beyond their applications in T cell biology, MHC tetramers prove valuable in investigating a spectrum of diseases such as infectious diseases, autoimmune disorders, and cancers. Their instrumental role extends to vaccine research and development. Notably, when appropriately configured, tetramers transcend T cell biology research and find utility in exploring natural killer T cells and contributing to specific T cell clonal deletions.

Author Info: (1) Centre of Experimental Medicine & Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. (2) Centre of Experimental Medicine & Surgery, Institute of

Author Info: (1) Centre of Experimental Medicine & Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. (2) Centre of Experimental Medicine & Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. (3) Centre of Experimental Medicine & Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. (4) Centre of Experimental Medicine & Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. (5) Centre of Experimental Medicine & Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. (6) Centre of Experimental Medicine & Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. Electronic address: rajiv.kumar@bhu.ac.in.

Atovaquone-Proguanil: A Promising Therapy for Persistent Relapsing Babesiosis

We report a challenging case of persistent relapsing babesiosis in an immunocompromised host that was successfully managed with atovaquone-proguanil (Malarone). Malignant B-cell transformation and immunosuppressants, such as rituximab, deplete normal B-cells which normally produce antibodies to combat Babesia infection. Treatment can be prolonged and challenging in immunocompromised hosts. Atovaquone-proguanil (Malarone) is a novel therapy that can be used as part of a salvage regimen in case antimicrobial resistance or failure exists. Weighing the risks and benefits of continuing cancer therapy treatment or reducing the level of immunosuppression may aid in treatment. These are just as important as the choice of antimicrobial therapy for effective treatment and eradication of Babesia infection, especially in immunocompromised hosts.

Author Info: (1) University of South Dakota Sanford School of Medicine, Vermillion, SD, USA. (2) University of Nebraska Medical Center, Department of Radiology, Omaha, NE, USA. (3) Avera Medica

Author Info: (1) University of South Dakota Sanford School of Medicine, Vermillion, SD, USA. (2) University of Nebraska Medical Center, Department of Radiology, Omaha, NE, USA. (3) Avera Medical Group, Oncology and Hematology Department, Sioux Falls, SD, USA. (4) University of South Dakota Sanford School of Medicine, Vermillion, SD, USA.

Conversion of dendritic cells into tolerogenic or inflammatory cells depends on the activation threshold and kinetics of the mTOR signaling pathway

BACKGROUND: Restoring impaired peripheral immune tolerance is the primary challenge in treating autoimmune diseases. Our previous research demonstrated the effectiveness of small spleen peptides (SSPs), a fraction of low molecular weight proteins, in inhibiting the progression of psoriatic arthritis, even in the presence of high levels of the proinflammatory cytokine TNF_ in the bloodstream. When specifically targeting dendritic cells (DCs), SSPs transform them into tolerogenic cells, which efficiently induce the development of regulatory Foxp3(+) Treg cells. In this study, we provide further insights into the mechanism of action of SSPs. RESULTS: We found that SSPs stimulate the activation of the mTOR signaling pathway in dendritic cells, albeit in a different manner than the classical immunogenic stimulus LPS. While LPS-induced activation is rapid, strong, and sustained, the activity induced by SSPs is delayed, less intense, yet still significant. These distinct patterns of activation, as measured by phosphorylation of key components of the pathway are also observed in response to other immunogenic and tolerogenic stimuli such as GM-CSF_+_IL-4 or IL-10 and TGF_. The disparity in mTOR activation between immunogenic and tolerogenic stimuli is quantitative rather than qualitative. In both cases, mTOR activation primarily occurs through the PI3K/Akt signaling axis and involves ERK and GSK3_ kinases, with minimal involvement of AMPK or NF-kB pathways. Furthermore, in the case of SSPs, mTOR activation seems to involve adenosine receptors. Additionally, we observed that DCs treated with SSPs exhibit an energy metabolism with high plasticity, which is typical of tolerogenic cells rather than immunogenic cells. CONCLUSION: Hence, the decision whether dendritic cells enter an inflammatory or tolerogenic state seems to rely on varying activation thresholds and kinetics of the mTOR signaling pathway.

Author Info: (1) Institute of Molecular Virology, Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms- University, Von-Esmarch-Str. 56, 48149, Muenster, Germany. vwixler

Author Info: (1) Institute of Molecular Virology, Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms- University, Von-Esmarch-Str. 56, 48149, Muenster, Germany. vwixler@uni-muenster.de. (2) Institute of Molecular Virology, Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms- University, Von-Esmarch-Str. 56, 48149, Muenster, Germany. (3) Institute of Molecular Virology, Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms- University, Von-Esmarch-Str. 56, 48149, Muenster, Germany. Department of Mental Health, Westfaelische Wilhelms-University, 48149, Muenster, Germany. (4) Pediatric Rheumatology and Immunology, University Children's Hospital Muenster, 48149, Muenster, Germany. (5) Institute of Molecular Virology, Centre for Molecular Biology of Inflammation (ZMBE), Westfaelische Wilhelms- University, Von-Esmarch-Str. 56, 48149, Muenster, Germany.

Next generation CD40 agonists for cancer immunotherapy

INTRODUCTION: There is a need for new therapies that can enhance response rates and broaden the number of cancer indications where immunotherapies provide clinical benefit. CD40 targeting therapies provide an opportunity to meet this need by promoting priming of tumor-specific T cells and reverting the suppressive tumor microenvironment. This is supported by emerging clinical evidence demonstrating the benefits of immunotherapy with CD40 antibodies in combination with standard of care chemotherapy. AREAS COVERED: This review is focused on the coming wave of next-generation CD40 agonists aiming to improve efficacy and safety, using new approaches and formats beyond monospecific antibodies. Further, the current understanding of the role of different CD40 expressing immune cell populations in the tumor microenvironment is reviewed. EXPERT OPINION: There are multiple promising next-generation approaches beyond monospecific antibodies targeting CD40 in immuno-oncology. Enhancing efficacy is the most important driver for this development, and approaches that maximize the ability of CD40 to both remodel the tumor microenvironment and boost the anti-tumor T cell response provide great opportunities to benefit cancer patients. Enhanced understanding of the role of different CD40 expressing immune cells in the tumor microenvironment may facilitate more efficient clinical development of these compounds.

Author Info: (1) Alligator Bioscience AB, Lund, Sweden. Department of Immunotechnology, Lund University, Lund, Sweden. (2) Alligator Bioscience AB, Lund, Sweden. Department of Biomedical Scienc

Author Info: (1) Alligator Bioscience AB, Lund, Sweden. Department of Immunotechnology, Lund University, Lund, Sweden. (2) Alligator Bioscience AB, Lund, Sweden. Department of Biomedical Science, Malmš University, Malmš, Sweden. (3) Department of Immunotechnology, Lund University, Lund, Sweden. (4) Alligator Bioscience AB, Lund, Sweden. (5) Alligator Bioscience AB, Lund, Sweden. (6) Alligator Bioscience AB, Lund, Sweden. Department of Immunotechnology, Lund University, Lund, Sweden. (7) Alligator Bioscience AB, Lund, Sweden. Department of Immunotechnology, Lund University, Lund, Sweden.

Pre-vaccination transcriptomic profiles of immune responders to the MUC1 peptide vaccine for colon cancer prevention

Self-antigens abnormally expressed on tumors, such as MUC1, have been targeted by therapeutic cancer vaccines. We recently assessed in two clinical trials in a preventative setting whether immunity induced with a MUC1 peptide vaccine could reduce high colon cancer risk in individuals with a history of premalignant colon adenomas. In both trials, there were immune responders and non-responders to the vaccine. Here we used PBMC pre-vaccination and 2 weeks after the first vaccine of responders and non-responders selected from both trials to identify early biomarkers of immune response involved in long-term memory generation and prevention of adenoma recurrence. We performed flow cytometry, phosflow, and differential gene expression analyses on PBMCs collected from MUC1 vaccine responders and non-responders pre-vaccination and two weeks after the first of three vaccine doses. MUC1 vaccine responders had higher frequencies of CD4 cells pre-vaccination, increased expression of CD40L on CD8 and CD4 T-cells, and a greater increase in ICOS expression on CD8 T-cells. Differential gene expression analysis revealed that iCOSL, PI3K AKT MTOR, and B-cell signaling pathways are activated early in response to the MUC1 vaccine. We identified six specific transcripts involved in elevated antigen presentation, B-cell activation, and NF-_B1 activation that were directly linked to finding antibody response at week 12. Finally, a model using these transcripts was able to predict non-responders with accuracy. These findings suggest that individuals who can be predicted to respond to the MUC1 vaccine, and potentially other vaccines, have greater readiness in all immune compartments to present and respond to antigens. Predictive biomarkers of MUC1 vaccine response may lead to more effective vaccines tailored to individuals with high risk for cancer but with varying immune fitness.

Author Info: (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11)

Author Info: (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11)

HHLA2 deficiency inhibits pancreatic cancer progression and THP-1 macrophage M2 polarization via EGFR/MAPK/ERK and mTOR/AKT pathway

BACKGROUND: Human endogenous retrovirus subfamily H long terminal repeat associating protein 2, (HHLA2), a member of B7 family, exhibits heightened expression in various malignant tumors. However, the exact functions of HHLA2 in pancreatic cancer (PC) remain incompletely elucidated. METHODS: We initially conducted an analysis of the B7 family members' expression pattern in pancreatic tumor samples and adjacent normal tissues using The Cancer Genome Atlas (TCGA) database. Subsequently, immunohistochemistry, RT-qPCR and western blot methods were used to assess HHLA2 expression levels in PC tissues and cell lines. Furthermore, after silencing HHLA2 in PC cell lines, cell migration and proliferation of PC cells were detected by wound healing and CCK-8 assays, and cell invasion of PC cells was detected by transwell assays. We also investigated the regulation of epithelial-mesenchymal transition (EMT) markers and levels of EGFR, MEK, ERK1/2, mTOR and AKT via western blot analysis. Finally, the correlation between HHLA2 expression and immune infiltration was further explored. RESULTS: Silencing of HHLA2 resulted in the inhibition of PC cell proliferation, migration and invasion, potentially through the suppression of the EGFR/MAPK/ERK and mTOR/AKT signaling pathway. Additionally, silencing HHLA2 led to the inhibition of M2-type polarization of tumor associated macrophages (TAMs). CONCLUSION: The knockdown of HHLA2 was observed to inhibit the migration and invasion of PC cells through the regulation of the EMT process and EGFR/MAPK/ERK and mTOR/AKT pathway. Furthermore, silencing HHLA2 was found to modulate M2 polarization of TAMs. These finding suggest that HHLA2 could be a promising therapeutic target for Pancreatic cancer.

Author Info: (1) Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, No.321, Zhongshan Road, Nanjing, 210008, China. Department of Gastroenterolo

Author Info: (1) Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, No.321, Zhongshan Road, Nanjing, 210008, China. Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China. (2) Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China. (3) State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China. (4) Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China. (5) Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, No.321, Zhongshan Road, Nanjing, 210008, China. zhangsgastro@nju.edu.cn. Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China. zhangsgastro@nju.edu.cn. (6) Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, No.99, Huaihai West Road, Xuzhou, 221000, China. zhpsqxt@163.com. (7) Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, No.321, Zhongshan Road, Nanjing, 210008, China. zouxp@nju.edu.cn. Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China. zouxp@nju.edu.cn.

Clinical application of immunogenic cell death inducers in cancer immunotherapy: turning cold tumors hot

Immunotherapy has emerged as a promising cancer treatment option in recent years. In immune "hot" tumors, characterized by abundant immune cell infiltration, immunotherapy can improve patients' prognosis by activating the function of immune cells. By contrast, immune "cold" tumors are often less sensitive to immunotherapy owing to low immunogenicity of tumor cells, an immune inhibitory tumor microenvironment, and a series of immune-escape mechanisms. Immunogenic cell death (ICD) is a promising cellular process to facilitate the transformation of immune "cold" tumors to immune "hot" tumors by eliciting innate and adaptive immune responses through the release of (or exposure to) damage-related molecular patterns. Accumulating evidence suggests that various traditional therapies can induce ICD, including chemotherapy, targeted therapy, radiotherapy, and photodynamic therapy. In this review, we summarize the biological mechanisms and hallmarks of ICD and introduce some newly discovered and technologically innovative inducers that activate the immune system at the molecular level. Furthermore, we also discuss the clinical applications of combing ICD inducers with cancer immunotherapy. This review will provide valuable insights into the future development of ICD-related combination therapeutics and potential management for "cold" tumors.

Author Info: (1) Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. (2) Department of Oncology, Shengjing Hospital of China Medical University, S

Author Info: (1) Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. (2) Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. (3) Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. (4) Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.

A non-lipid nucleic acid delivery vector with dendritic cell tropism and stimulation

Rationale: Nucleic acid constructs are commonly used for vaccination, immune stimulation, and gene therapy, but their use in cancer still remains limited. One of the reasons is that systemic delivery to tumor-associated antigen-presenting cells (dendritic cells and macrophages) is often inefficient, while off-target nucleic acid-sensing immune pathways can stimulate systemic immune responses. Conversely, certain carbohydrate nanoparticles with small molecule payloads have been shown to target these cells efficiently in the tumor microenvironment. Yet, nucleic acid incorporation into such carbohydrate-based nanoparticles has proven challenging. Methods: We developed a novel approach using cross-linked bis succinyl-cyclodextrin (b-s-CD) nanoparticles to efficiently deliver nucleic acids and small-molecule immune enhancer to phagocytic cells in tumor environments and lymph nodes. Our study involved incorporating these components into the nanoparticles and assessing their efficacy in activating antigen-presenting cells. Results: The multi-modality immune stimulators effectively activated antigen-presenting cells and promoted anti-tumor immunity in vivo. This was evidenced by enhanced delivery to phagocytic cells and subsequent immune response activation in tumor environments and lymph nodes. Conclusion: Here, we describe a new approach to incorporating both nucleic acids and small-molecule immune enhancers into cross-linked bis succinyl-cyclodextrin (b-s-CD) nanoparticles for efficient delivery to phagocytic cells in tumor environments and lymph nodes in vivo. These multi-modality immune stimulators can activate antigen-presenting cells and foster anti-tumor immunity. We argue that this strategy can potentially be used to enhance anti-tumor efficacy.

Author Info: (1) Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114, USA. Department of Systems Biology, Harvard Medical School, 200 Longw

Author Info: (1) Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114, USA. Department of Systems Biology, Harvard Medical School, 200 Longwood Ave, Boston, MA 02115, USA. Harvard Master's Program in Immunology, Harvard Medical School, 200 Longwood Ave, Boston, MA 02114, USA. (2) Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114, USA. Department of Systems Biology, Harvard Medical School, 200 Longwood Ave, Boston, MA 02115, USA. Harvard Master's Program in Immunology, Harvard Medical School, 200 Longwood Ave, Boston, MA 02114, USA. (3) Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114, USA. Department of Systems Biology, Harvard Medical School, 200 Longwood Ave, Boston, MA 02115, USA. Harvard Master's Program in Immunology, Harvard Medical School, 200 Longwood Ave, Boston, MA 02114, USA. (4) Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114, USA. Department of Systems Biology, Harvard Medical School, 200 Longwood Ave, Boston, MA 02115, USA. Harvard Master's Program in Immunology, Harvard Medical School, 200 Longwood Ave, Boston, MA 02114, USA. (5) Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114, USA. Department of Systems Biology, Harvard Medical School, 200 Longwood Ave, Boston, MA 02115, USA. Harvard Master's Program in Immunology, Harvard Medical School, 200 Longwood Ave, Boston, MA 02114, USA. (6) Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114, USA. Department of Systems Biology, Harvard Medical School, 200 Longwood Ave, Boston, MA 02115, USA. Harvard Master's Program in Immunology, Harvard Medical School, 200 Longwood Ave, Boston, MA 02114, USA. (7) Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114, USA. Department of Systems Biology, Harvard Medical School, 200 Longwood Ave, Boston, MA 02115, USA. Harvard Master's Program in Immunology, Harvard Medical School, 200 Longwood Ave, Boston, MA 02114, USA.

Sequence of androgen receptor-targeted vaccination with androgen deprivation therapy affects anti-prostate tumor efficacy

RATIONALE: Androgen deprivation therapy (ADT) is the primary treatment for recurrent and metastatic prostate cancer. In addition to direct antitumor effects, ADT has immunomodulatory effects such as promoting T-cell infiltration and enhancing antigen processing/presentation. Previous studies in our laboratory have demonstrated that ADT also leads to increased expression of the androgen receptor (AR) and increased recognition of prostate tumor cells by AR-specific CD8+T cells. We have also demonstrated that ADT combined with a DNA vaccine encoding the AR significantly slowed tumor growth and improved the survival of prostate tumor-bearing mice. The current study aimed to investigate the impact of the timing and sequencing of ADT with vaccination on the tumor immune microenvironment in murine prostate cancer models to further increase the antitumor efficacy of vaccines. METHODS: Male FVB mice implanted with Myc-CaP tumor cells, or male C57BL/6 mice implanted with TRAMP-C1 prostate tumor cells, were treated with a DNA vaccine encoding AR (pTVG-AR) and ADT. The sequence of administration was evaluated for its effect on tumor growth, and tumor-infiltrating immune populations were characterized. RESULTS: Vaccination prior to ADT (pTVG-AR _ ADT) significantly enhanced antitumor responses and survival. This was associated with increased tumor infiltration by CD4+ and_CD8+ T cells, including AR-specific CD8+T cells. Depletion of CD8+T cells prior to ADT significantly worsened overall survival. Following ADT treatment, however, Gr1+ myeloid-derived suppressor cells (MDSCs) increased, and this was associated with fewer infiltrating T cells and reduced tumor growth. Inhibiting Gr1+MDSCs recruitment, either by using a CXCR2 antagonist or by cycling androgen deprivation with testosterone replacement, improved antitumor responses and overall survival. CONCLUSION: Vaccination prior to ADT significantly improved antitumor responses, mediated in part by increased infiltration of CD8+T cells following ADT. Targeting MDSC recruitment following ADT further enhanced antitumor responses. These findings suggest logical directions for future clinical trials to improve the efficacy of prostate cancer vaccines.

Author Info: (1) Cancer Biology, University of Wisconsin-Madison, Madison, Wisconsin, USA. (2) UW Carbone Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin, USA. (3) UW Carbone

Author Info: (1) Cancer Biology, University of Wisconsin-Madison, Madison, Wisconsin, USA. (2) UW Carbone Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin, USA. (3) UW Carbone Cancer Center, University of Wisconsin-Madison, Madison, Wisconsin, USA. (4) Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA dm3@medicine.wisc.edu.

Dual role of the peptide-loading complex as proofreader and limiter of MHC-I presentation

Antigen presentation via major histocompatibility complex class I (MHC-I) molecules is essential for surveillance by the adaptive immune system. Central to this process is the peptide-loading complex (PLC), which translocates peptides from the cytosol to the endoplasmic reticulum and catalyzes peptide loading and proofreading of peptide-MHC-I (pMHC-I) complexes. Despite its importance, the impact of individual PLC components on the presented pMHC-I complexes is still insufficiently understood. Here, we used stoichiometrically defined antibody-nanobody complexes and engineered soluble T cell receptors (sTCRs) to quantify different MHC-I allomorphs and defined pMHC-I complexes, respectively. Thereby, we uncovered distinct effects of individual PLC components on the pMHC-I surface pool. Knockouts of components of the PLC editing modules, namely tapasin, ERp57, or calreticulin, changed the MHC-I surface composition to a reduced proportion of HLA-A*02:01 presentation compensated by a higher ratio of HLA-B*40:01 molecules. Intriguingly, these knockouts not only increased the presentation of suboptimally loaded HLA-A*02:01 complexes but also elevated the presentation of high-affinity peptides overexpressed in the cytosol. Our findings suggest that the components of the PLC editing module serve a dual role, acting not only as peptide proofreaders but also as limiters for abundant peptides. This dual function ensures the presentation of a broad spectrum of antigenic peptides.

Author Info: (1) Institute of Biochemistry, Biocenter, Goethe University Frankfurt, Frankfurt am Main 60438, Germany. (2) Institute of Biochemistry, Biocenter, Goethe University Frankfurt, Fran

Author Info: (1) Institute of Biochemistry, Biocenter, Goethe University Frankfurt, Frankfurt am Main 60438, Germany. (2) Institute of Biochemistry, Biocenter, Goethe University Frankfurt, Frankfurt am Main 60438, Germany. (3) Institute of Biochemistry, Biocenter, Goethe University Frankfurt, Frankfurt am Main 60438, Germany. (4) Institute of Biochemistry, Biocenter, Goethe University Frankfurt, Frankfurt am Main 60438, Germany. (5) Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna 1090, Austria. (6) Immunocore Ltd., Abingdon OX14 4RY, United Kingdom. (7) Immunocore Ltd., Abingdon OX14 4RY, United Kingdom. (8) Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna 1090, Austria. (9) Institute of Biochemistry, Biocenter, Goethe University Frankfurt, Frankfurt am Main 60438, Germany.

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