Cancer immunotherapy strategies based on overcoming barriers within the tumor microenvironment.

Cancer immunotherapy strategies based on overcoming barriers within the tumor microenvironment. Curr Opin Immunol. 2013 Apr;25(2):268-76 Authors: Gajewski TF, Woo SR, Zha Y, Spaapen R, Zheng Y, Corrales L, Spranger S Abstract For tumor antigen-specific T cells to effectively control the growth of cancer cells in vivo, they must gain access to, and function within, the tumor microenvironment. While tumor antigen-based vaccines and T cell adoptive transfer strategies can result in clinical benefit in a subset of patients, most of the patients do not respond clinically. Even for tumor-infiltrating lymphocyte (TIL)-based adoptive transfer for patients with metastatic melanoma, which can provide tumor shrinkage in around 50% of treated individuals, many patients are not eligible, in part because there are not sufficient TIL present in the resected tumor. Thus, the denominator is in fact larger, and it has been suggested that absence of TIL may be a marker for poor efficacy of immunotherapies in general. While qualitative and/or quantitative features of the T cells are important considerations for efficacy, a major component of primary resistance likely can be attributed to the tumor microenvironment. Data are accumulating suggesting that two major categories of immune resistance within the tumor microenvironment may exist: failure of T cell trafficking due to low levels of inflammation and lack of chemokines for migration, and dominant suppression through immune i...
Source: Current Opinion in Immunology - Category: Allergy & Immunology Authors: Tags: Curr Opin Immunol Source Type: research

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T cell cancer neoantigens are created from peptides derived from cancer-specific aberrant proteins, such as mutated and fusion proteins, presented in complex with human leukocyte antigens on the cancer cell surface. Because expression of the aberrant target protein is exclusive to malignant cells, immunotherapy directed against neoantigens should avoid “on-target, off-tumor” toxicity. The efficacy of neoantigen vaccines in melanoma and glioblastoma and of adoptive transfer of neoantigen-specific T cells in epithelial tumors indicates that neoantigens are valid therapeutic targets. Improvements in sequencing tec...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
AbstractBackgroundAutologous dendritic cells (DC) loaded with tumor-associated antigens (TAAs) are a promising approach for anticancer immunotherapy. Polyantigen lysates appear to be an excellent source of TAAs for loading onto the patient ’s dendritic cells. Cancer/testis antigens (CTA) are expressed by a wide range of tumors, but are minimally expressed on normal tissues, and could serve as a universal target for immunotherapy. However, CTA expression levels can vary significantly in patients with the same tumor type. We proposed that patients who do not respond to DC-based therapy may have distinct features of the...
Source: Clinical Sarcoma Research - Category: Cancer & Oncology Source Type: research
Cutaneous melanoma, also called malignant melanoma, is the type of skin cancer that is most likely to spread to other parts of the body. Though melanoma accounts for only about 1% of skin cancers, it is responsible for more than 90% of skin cancer-related deaths. But thanks to developments in skin cancer treatment (mostly in the last decade), patients with melanoma have much better chances of living longer. What is a melanoma? Melanoma involves the uncontrolled growth of a type of cell known as a melanocyte. One of the most important functions of a normal melanocyte is to protect your skin from the sun’s damaging ult...
Source: Harvard Health Blog - Category: Consumer Health News Authors: Tags: Cancer Skin and Hair Care Source Type: blogs
ONCOS-102, a promising immunotherapy vaccine, is moving closer to becoming a part of future first-line treatment for mesothelioma. Early clinical trial results announced this week show safety and efficacy when the vaccine is used in combination with standard-of-care chemotherapy for patients with inoperable pleural mesothelioma. Targovax, a Scandinavian pharmaceutical company developing the drug, is moving forward with another study combining ONCOS-102 with a checkpoint inhibitor drug such as Keytruda (pembrolizumab) or Opdivo (nivolumab), along with chemotherapy. “We have seen enough data at this point to be going ...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
ConclusionsCombination of DC vaccination and cisplatin in melanoma patients is feasible and safe, but does not seem to result in more tumor-specific T cell responses or improved clinical outcome, when compared to DC vaccination monotherapy.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
ConclusionsEfficient targeting of antigen to immature dendritic cells with a chemokine-fusion vaccine offers an alternative to classic and dendritic cell vaccines. Combining this approach with IFN α and 5Aza treatment significantly improved vaccine efficacy. This improved efficacy correlated with changes in chemokine gene expression and CD8+ TIL infiltration and was dependent on the presence of all therapeutic components.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
This study provides strong evidence that following a healthy lifestyle can substantially extend the years a person lives disease-free." Commentary on Recent Evidence for Cognitive Decline to Precede Amyloid Aggregation in Alzheimer's Disease https://www.fightaging.org/archives/2020/01/commentary-on-recent-evidence-for-cognitive-decline-to-precede-amyloid-aggregation-in-alzheimers-disease/ I can't say that I think the data presented in the research noted here merits quite the degree of the attention that it has been given in the popular science press. It is interesting, but not compelling if its role...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Authors: Flores I, Hevia D, Tittarelli A, Soto D, Rojas-Sepúlveda D, Pereda C, Tempio F, Fuentes C, Falcón-Beas C, Gatica J, Falcón-Beas F, Galindo M, Salazar-Onfray F, González FE, López MN Abstract Ovarian epithelial carcinoma (OEC) is the most frequent ovarian tumor, characterized by a high mortality in advanced stages where conventional therapies are not effective. Based on the role of the immune system in the progression of this disease, immunotherapy using checkpoint blockade has been considered as a therapeutic alternative. Nevertheless, its results do not match up to the p...
Source: Journal of Immunology Research - Category: Allergy & Immunology Tags: J Immunol Res Source Type: research
Treatments that generate T cell-mediated immunity to a patient ’s unique neoantigens are the current holy grail of cancer immunotherapy. In particular, treatments that do not require cumbersome and individualiz...
Source: Cancer Cell International - Category: Cancer & Oncology Authors: Tags: Primary research Source Type: research
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
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