A5035857875- Immunotherapy and Immune Responses
- Melanoma and MAPK Pathways
- CAR-T cell therapy research
- melanin and skin pigmentation
- Cytokine Signaling Pathways and Interactions
- Cancer Immunotherapy and Biomarkers
- interferon and immune responses
- Cancer Research and Treatments
- T-cell and B-cell Immunology
- Atherosclerosis and Cardiovascular Diseases
- Monoclonal and Polyclonal Antibodies Research
- Chemokine receptors and signaling
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- vaccines and immunoinformatics approaches
- Protein Degradation and Inhibitors
- Sarcoma Diagnosis and Treatment
- Computational Drug Discovery Methods
Copenhagen University Hospital
2022-2025
Herlev Hospital
2023-2024
Background Neoantigens can serve as targets for T cell-mediated antitumor immunity via personalized neopeptide vaccines. Interim data from our clinical study NCT03715985 showed that the peptide-based neoantigen vaccine EVX-01, formulated in liposomal adjuvant, CAF09b, was safe and able to elicit EVX-01-specific cell responses patients with metastatic melanoma. Here, we present results dose-escalation part of study, evaluating feasibility, safety, efficacy, immunogenicity EVX-01 addition...
LTX-315 is an oncolytic peptide that elicits both local and systemic immune responses upon intratumoral injection. In the present pilot trial, we treated patients with metastatic soft tissue sarcoma combination of adoptive T-cell therapy using in vitro expanded tumor-infiltrating lymphocytes. Six heavily pretreated were included trial which four proceeded to therapy. Overall, treatment was considered safe only expected manageable toxicity. The best overall clinical response stable disease...
Abstract Purpose: Impaired MHCI-presentation and insensitivity to immune effector molecules are common features of checkpoint blockade (ICB)-resistant tumors can be, respectively, associated with loss β2 microglobulin (B2M) or impaired IFNγ signaling. Patients ICB-resistant respond alternative immunotherapies, such as infusion autologous tumor-infiltrating lymphocytes (TIL). CD4+ T cells exert cytotoxic functions against tumor cells; however, it is unclear whether T-cell responses be...
9518 Background: Metastatic melanoma refractory to immune checkpoint inhibitors (ICI) remains a significant challenge. Adoptive Cell Transfer of Tumor-Infiltrating Lymphocytes (ACT-TILs) shows promise but can cause adverse events. Oncolytic adenovirus TILT-123 (igrelimogene litadenorepvec) coding for TNF and IL2 combined with ACT-TILs, offers an approach without conditioning therapies. We report long-term survival data from phase I trial (TUNINTIL NCT04217473), correlative clinical,...
Background The B-cell lymphoma-extra-large (Bcl-XL) protein plays an important role in cancer cells’ resistance to apoptosis. Pre-clinical studies have shown that vaccination with Bcl-XL-derived peptides can induce tumor-specific T cell responses may lead the elimination of cells. Furthermore, pre-clinical novel adjuvant CAF ® 09b intraperitoneal (IP) injections this improve activation immune system. In study, patients hormone-sensitive prostate (PC) received a vaccine consisting...
Highlights•TILT-123 plus TILs mediate complete remission in a patient with mucosal melanoma.•Tumor biopsies revealed increased infiltration of CD4+ and CD8+ T cells.•Indications clinical efficacy TILT-123 alone were observed.•The combination is promising new treatment modality.AbstractBackgroundDespite significant advancements the malignant melanoma, metastatic melanoma remains therapeutic challenge due to its complex pathogenesis, distinct pathological characteristics, limited response...
9551 Background: Despite the advances made with CPIs such as aPD-1/aPD-L1, aCTL4 and aLAG-3 there still is a significant unmet medical need for patients metastatic cancers. As it has been shown that effect of are mediated by tumor specific T cells, one strategy increasing treatment success to actively induce cells. Here, we report on first-in-human clinical trial evaluating personalized neoantigen vaccine (EVX-01) in melanoma. Methods: Stage-IV melanoma were treated standard aPD-1...
11567 Background: Adoptive cell transfer (ACT) with tumor-infiltrating lymphocytes (TILs) is a potent treatment that can induce complete and durable tumor regression as documented in patients metastatic melanoma. To our knowledge, ACT has not been utilized for soft-tissue sarcoma (STS). LTX-315 an oncolytic peptide shown to increase TILs malignant tumors after intratumoral injection. In this trial, were treated the combination of TIL - based ACT. Methods: Patients progressive STS minimum one...
Tumor Infiltrating Lymphocyte (TIL) therapy has recently proved effective in patients with metastatic melanoma. Oncolytic adenovirus TILT-123 (igrelimogene litadenorepvec) is armed tumor necrosis factor-alpha and interleukin-2 which were selected specifically for their ability to enhance TIL cytotoxicity without the need preconditioning chemotherapy or postconditioning IL2. In a phase I, open-label, 3+3 dose-escalating multicenter trial, stage IV melanoma treated multiple intravenous...
<div>Abstract<p>Introduction: Impaired MHCI-presentation and insensitivity to immune effector molecules are common features of checkpoint blockade(ICB)-resistant tumors can be respectively associated with loss β<sub>2</sub> microglobulin(B2M) or impaired IFNγ-signaling. Patients ICB-resistant respond alternative immunotherapies, such as infusion autologous tumor-infiltrating lymphocytes(TILs). CD4<sup>+</sup> T cells exert cytotoxic functions against tumor...
<p>Supplementary Figures and Tables</p>
<p>CD4+ TILs from melanoma can exert cytotoxic activity against autologous tumor cells (GFP+TCL#17)</p>
<p>CD4+ TIL-mediated killing is dependent on MHC Class II expression (TCL#17)</p>
<p>CD4+ TIL-mediated killing is dependent on MHC Class II expression (TCL#17)</p>
<p>CD4+ TILs can exert cytotoxicity against JAK1KO MHCIIConst+ tumors even in absence of IFNγ stimulation (TCL#17)</p>
<p>CD4+ TILs from melanoma can exert cytotoxic activity against autologous tumor cells (GFP+TCL#17)</p>
<p>Supplementary Figures and Tables</p>
<p>CD4+ TILs can exert cytotoxicity against JAK1KO MHCIIConst+ tumors even in absence of IFNγ stimulation (TCL#17)</p>
<h3>Background</h3> Adoptive cell therapy (ACT) with tumour-infiltrating lymphocytes (TILs) entails the isolation, expansion, and reinfusion of autologous TILs to enhance immune system's ability recognize eradicate tumour cells. Mutations in cells may lead generation neoantigens which display various degrees homology common microbial antigens. We therefore decided investigate whether efficacy cancer immunotherapy, observed some patients, might be contributable boosting an existing...
<h3>Background</h3> Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by enhancing the immune system's ability to recognize and attack tumors. However, their use is frequently accompanied immune-related adverse events (irAEs), which can significantly impact patient quality of life necessitate discontinuation. Moreover, only few studies been focused on management these irAEs. The current strategy consists primarily corticosteroids, are immunosuppressive drugs that also...
<p>CD4+ TILs from melanoma can exert cytotoxic activity against autologous tumor cells (GFP+TCL#17)</p>
<div>Abstract<p>Introduction: Impaired MHCI-presentation and insensitivity to immune effector molecules are common features of checkpoint blockade(ICB)-resistant tumors can be respectively associated with loss β<sub>2</sub> microglobulin(B2M) or impaired IFNγ-signaling. Patients ICB-resistant respond alternative immunotherapies, such as infusion autologous tumor-infiltrating lymphocytes(TILs). CD4<sup>+</sup> T cells exert cytotoxic functions against tumor...
<p>Supplementary Figures and Tables</p>
<p>CD4+ TILs can exert cytotoxicity against JAK1KO MHCIIConst+ tumors even in absence of IFNγ stimulation (TCL#17)</p>