Immunological ignorance is an enabling feature of the oligo-clonal T cell response to melanoma neoantigens Immunology and Inflammation

The impact of intratumoral heterogeneity (ITH) and the resultant neoantigen landscape on T cell immunity are poorly understood. ITH is a widely recognized feature of solid tumors and poses distinct challenges related to the development of effective therapeutic strategies, including cancer neoantigen vaccines. Here, we performed deep targeted DNA sequencing...
Source: Proceedings of the National Academy of Sciences - Category: Science Authors: Tags: PNAS Plus 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
CONCLUSIONS: Multiple tumor-specific cell surface-related neoantigens were abundant in B16-F10 cells. Antibodies to 9 of these neoantigens had variable binding but when combined had dense homogeneous binding. Even one dose of this cocktail of 9 antibodies improved survival and when multiple doses were combined with PD1 inhibition 50% of the mice were rendered permanently tumor free. PMID: 31812660 [PubMed - as supplied by publisher]
Source: Journal of Immunological Methods - Category: Allergy & Immunology Authors: Tags: J Immunol Methods 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
Angiopoietin-like protein 2 (ANGPTL2) is a secreted glycoprotein homologous to angiopoietins. Previous studies suggest that tumor cell-derived ANGPTL2 has tumor-promoting function. Here, we conducted mechanistic analysis comparing ANGPTL2 function in cancer progression in a murine syngeneic model of melanoma and a mouse model of translocation renal cell carcinoma (tRCC). ANGPTL2 deficiency in tumor cells slowed tRCC progression, supporting a tumor-promoting role. However, systemic ablation of ANGPTL2 accelerated tRCC progression, supporting a tumor-suppressing role. The syngeneic model also demonstrated a tumor-suppressing...
Source: Genes and Development - Category: Genetics & Stem Cells Authors: Tags: Research Papers Source Type: research
Conditions:   Melanoma;   Kidney Cancer Intervention:   Biological: Tag-7 gene modified inactivated tumor cells Sponsors:   N.N. Petrov National Medical Research Center of Oncology;   Institute of Gene Biology Russian Academy of Sciences Completed
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conditions:   Melanoma;   Kidney Cancer Intervention:   Biological: Tag-7 gene modified inactivated tumor cells Sponsors:   N.N. Petrov National Medical Research Center of Oncology;   Institute of Gene Biology Russian Academy of Sciences Completed
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conditions:   Melanoma;   Kidney Cancer Intervention:   Biological: Tag-7 gene modified inactivated tumor cells Sponsors:   N.N. Petrov National Medical Research Center of Oncology;   Institute of Gene Biology Russian Academy of Sciences Completed
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conditions:   Melanoma;   Kidney Cancer Intervention:   Biological: Tag-7 gene modified inactivated tumor cells Sponsors:   N.N. Petrov National Medical Research Center of Oncology;   Institute of Gene Biology Russian Academy of Sciences Completed
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conditions:   Melanoma;   Kidney Cancer Intervention:   Biological: Tag-7 gene modified inactivated tumor cells Sponsors:   N.N. Petrov National Medical Research Center of Oncology;   Institute of Gene Biology Russian Academy of Sciences Completed
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Farzaneh Ioannis P. Trougakos Wolfgang Voelter Meletios-Athanasios Dimopoulos Aristotelis Bamias Ourania Tsitsilonis Prothymosin α (proTα) and its C-terminal decapeptide proTα(100–109) were shown to pleiotropically enhance innate and adaptive immune responses. Their activities have been broadly studied in vitro, focusing primarily on the restoration of the deficient immunoreactivity of cancer patients’ leukocytes. Previously, we showed that proTα and proTα(100–109) act as danger-associated molecular patterns (DAMPs), ligate Toll-l...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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