Secondary resistance to immunotherapy associated with β-catenin pathway activation or PTEN loss in metastatic melanoma

ConclusionOur results suggest that secondary resistance to immunotherapies can arise upon selection for new oncogenic variants that mediate T cell exclusion. To identify the spectrum of underlying mechanisms of therapeutic resistance, similar evaluation for the emergence of tumor-intrinsic alterations in resistant lesions should be done prospectively at the time of relapse in a range of additional patients developing secondary resistance.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research

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ConclusionsThese data suggest that a combined innate and adaptive immunotherapeutic approach can be effective against immunologically cold syngeneic murine neuroblastoma. Further testing is needed to determine how these concepts might translate into development of more effective immunotherapeutic approaches for the treatment of clinically high-risk neuroblastoma.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
We describe a model-based design strategy that was developed for a trial evaluating the safety and immunogenicity of vaccination with (1) peptides plus CD40 antibody and TLR3 ligand, (2) systemic administration of an agonistic CD27 antibody, and (3) to assess immune response from (1) and (2) compared to optimal controls in participants with stage IIB-IV melanoma.Results and conclusionsThe proposed design is a practical adaptive method for use with combined immunotherapy regimens with multiple objectives within multiple cohorts of interest. Further advances in the effectiveness of cancer immunotherapies will require new app...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
Tumor neoantigens are ideal targets for cancer immunotherapy as they are recognized by host immune system as foreigners and can elicit tumor-specific immune responses. However, existing strategies utilizing RNA or long peptides for the neoantigen vaccines render limited immune responses since only 20–30% of neoantigens predicted in silico to bind MHC I molecules are capable of eliciting immune responses with the majority of responding T cells are CD4+. Therefore, it warrants further exploration to enhance neoantigen-specific CD8+ T cells responses. Since neoantigens are naturally weak antigens, we asked whether forei...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
ConclusionsIn summary,pTuneos provides the state-of-the-art one-stop and user-friendly solution for prioritizing SNV-based candidate neoepitopes, which could help to advance research on next-generation cancer immunotherapies and personalized cancer vaccines.pTuneos is available athttps://github.com/bm2-lab/pTuneos, with a Docker version for quick deployment athttps://cloud.docker.com/u/bm2lab/repository/docker/bm2lab/ptuneos.
Source: Genome Medicine - Category: Genetics & Stem Cells Source Type: research
Dendritic cell (DC)-based vaccination effectively induces anti-tumor immunity, although in the majority of cases this does not translate into a durable clinical response. However, DC vaccination is characterized by a robust safety profile, making this treatment a potential candidate for effective combination cancer immunotherapy. To explore this possibility, understanding changes occurring in the tumor microenvironment (TME) upon DC vaccination is required. In this line, quantitative and qualitative changes in tumor-infiltrating T lymphocytes (TILs) induced by vaccination with autologous tumor lysate/homogenate loaded DCs ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
ConclusionsThese data suggest that peripheral blood TCRB convergence may serve as a predictive or prognostic biomarker for response to dendritic cell-based immunotherapy. Our finding of increased T cell clonal expansion at week 5 of treatment supports the notion that TCR sequencing may serve as a tool for the measurement of pharmacodynamic markers of therapeutic agent activity. Ongoing and future studies will further clarify the utility of TCR convergence and clonal expansion as immune repertoire biomarkers.Clinical trial identificationNCT01876212.Legal entity responsible for the studyUniversity of Pittsburgh School of Med...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsThis 5-year analysis represents the longest phase III follow-up for checkpoint inhibitor combination therapy and demonstrates long-term survival with both NIVO-containing arms vs IPI. In descriptive analyses, NIVO+IPI was associated with improved survival and a higher likelihood of being alive and treatment-free compared with NIVO alone, both without loss of QoL.Clinical trial identificationNCT01844505.Editorial acknowledgementWriting and editorial assistance was provided by Melissa Kirk, PhD, and Michele Salernitano of StemScientific, an Ashfield Company.Legal entity responsible for the studyBristol-Myers Squib...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
This article reviews the association between the immune system and cancer, as well as the additional systemic benefit that SBRT can have in patients with advanced-stage malignancies being treated with immunotherapy. PMID: 31549973 [PubMed - in process]
Source: Clinical Advances in Hematology and Oncology - Category: Cancer & Oncology Tags: Clin Adv Hematol Oncol Source Type: research
Publication date: 3 September 2019Source: Cell Reports, Volume 28, Issue 10Author(s): Songming Peng, Jesse M. Zaretsky, Alphonsus H.C. Ng, William Chour, Michael T. Bethune, Jongchan Choi, Alice Hsu, Elizabeth Holman, Xiaozhe Ding, Katherine Guo, Jungwoo Kim, Alexander M. Xu, John E. Heath, Won Jun Noh, Jing Zhou, Yapeng Su, Yue Lu, Jami McLaughlin, Donghui Cheng, Owen N. WitteSummaryNeoantigen-specific T cells are increasingly viewed as important immunotherapy effectors, but physically isolating these rare cell populations is challenging. Here, we describe a sensitive method for the enumeration and isolation of neoan...
Source: Cell Reports - Category: Cytology Source Type: research
In this study we generated tumor-derived apoptotic extracellular vesicles (ApoEVs), which are potentially an abundant source of tumor-specific neo-antigens and other tumor-associated antigens (TAAs), and which can be manipulated to express DC-targeting ligands for efficient antigen delivery. Our data demonstrates that by specifically modifying the glycocalyx of tumor cells, high-mannose glycans can be expressed on their cell surface and on extracellular vesicles derived after the induction of apoptosis. High-mannose glycans are the natural ligands of dendritic cell-specific intercellular adhesion molecule-3-grabbing non-in...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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