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First-line treatment for patients with advanced non-small cell lung carcinoma and high PD-L1 expression: pembrolizumab or pembrolizumab plus chemotherapy
In conclusion, the addition of chemotherapy to pembrolizumab further improves the outcomes of patients with advanced NSCLC and a PD-L1 TPS of at least 50%. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - May 2, 2019 Category: Cancer & Oncology Source Type: research

Immunotherapeutic effects of intratumoral nanoplexed poly I:C
AbstractPoly I:C is a powerful immune adjuvant as a result of its agonist activities on TLR-3, MDA5 and RIG-I. BO-112 is a nanoplexed formulation of Poly I:C complexed with polyethylenimine that causes tumor cell apoptosis showing immunogenic cell death features and which upon intratumoral release results in more prominent tumor infiltration by T lymphocytes. Intratumoral treatment with BO-112 of subcutaneous tumors derived from MC38, 4  T1 and B16-F10 leads to remarkable local disease control dependent on type-1 interferon and gamma-interferon. Some degree of control of non-injected tumor lesions following BO-112 intrat...
Source: Journal for Immunotherapy of Cancer - May 1, 2019 Category: Cancer & Oncology Source Type: research

Haemophagocytic lymphohistiocytosis in patients treated with immune checkpoint inhibitors: analysis of WHO global database of individual case safety reports
ConclusionsBy evaluating the largest cohort of ICI-related HLH cases, we observed that ICI-related HLH arises with a delayed timing with respect to initiation of ICI treatment, and usually presents without other irAEs and concomitant infections. Keeping in mind these findings, clinicians should consider ICIs ’ involvement in the onset of HLH whenever they diagnose a disease of this group of syndromes in cancer patients treated with ICIs. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - May 1, 2019 Category: Cancer & Oncology Source Type: research

STING agonist inflames the pancreatic cancer immune microenvironment and reduces tumor burden in mouse models
AbstractPancreatic cancer is characterized by an immune suppressive stromal reaction that creates a barrier to therapy. A murine transgenic pancreatic cancer cell line that recapitulates human disease was used to test whether a STimulator of Interferon Genes (STING) agonist could reignite immunologically inert pancreatic tumors. STING agonist treatment potently changed the tumor architecture, altered the immune profile, and increased the survival of tumor-bearing mice. Notably, STING agonist increased numbers and activity of cytotoxic T cells within tumors and decreased levels of suppressive regulatory T cells. Further, ST...
Source: Journal for Immunotherapy of Cancer - April 28, 2019 Category: Cancer & Oncology Source Type: research

Vaccination with nanoparticles combined with micro-adjuvants protects against cancer
ConclusionThe combination of nano- and micro-particles may optimally harness the physiological properties of the lymphatic system. Since the nanoparticles are well defined virus-like particles and the micron-sized adjuvant MCT has been used for decades in allergen-specific desensitization, this approach may readily be translated to the clinic. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 25, 2019 Category: Cancer & Oncology Source Type: research

Multiple antigen-engineered DC vaccines with or without IFN α to promote antitumor immunity in melanoma
ConclusionsDC vaccines are a safe and reliable platform for promoting antitumor immunity. This combination with one month of high dose IFN α did not improve outcomes. Immune biomarker analysis in the blood identified several predictive and prognostic biomarkers for further analysis, including MDSC.Trial registrationNCT01622933. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 23, 2019 Category: Cancer & Oncology Source Type: research

Pneumonitis resulting from radiation and immune checkpoint blockade illustrates characteristic clinical, radiologic and circulating biomarker features
ConclusionsThese data highlight the imaging findings associated with radiation and ICB-related lung toxicity, and anecdotally describe a clinical course with circulating biomarker correlates. This information can help guide clinical evaluation and future research investigations into the toxicity of combined radiation immunotherapy approaches. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 23, 2019 Category: Cancer & Oncology Source Type: research

STIM1 at the plasma membrane as a new target in progressive chronic lymphocytic leukemia
ConclusionsThese data establish the critical role of a newly discovered BCR independent Ca2+ entry in CLL evolution, provide new insights into CLL pathophysiology, and support innovative therapeutic perspectives such as targeting STIM1 located at the plasma membrane. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 22, 2019 Category: Cancer & Oncology Source Type: research

Split tolerance permits safe Ad5-GUCY2C-PADRE vaccine-induced T-cell responses in colon cancer patients
ConclusionsSplit tolerance to GUCY2C in cancer patients can be exploited to safely generate antigen-specific cytotoxic CD8+, but not autoimmune CD4+, T cells by Ad5-GUCY2C-PADRE in the absence of pre-existing NAbs to the viral vector.Trial registrationThis trial (NCT01972737) was registered atClinicalTrials.gov on October 30th, 2013.https://clinicaltrials.gov/ct2/show/NCT01972737 (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 22, 2019 Category: Cancer & Oncology Source Type: research

The clinical application of cancer immunotherapy based on naturally circulating dendritic cells
AbstractDendritic cells (DCs) can initiate and direct adaptive immune responses. This ability is exploitable in DC vaccination strategies, in which DCs are educated ex vivo to present tumor antigens and are administered into the patient with the aim to induce a tumor-specific immune response. DC vaccination remains a promising approach with the potential to further improve cancer immunotherapy with little or no evidence of treatment-limiting toxicity. However, evidence for objective clinical antitumor activity of DC vaccination is currently limited, hampering the clinical implementation. One possible explanation for this i...
Source: Journal for Immunotherapy of Cancer - April 17, 2019 Category: Cancer & Oncology Source Type: research

Treatment of malignant pleural effusions: the case for localized immunotherapy
AbstractMalignant pleural effusions (MPE) are a common terminal pathway for many cancers, with an estimated United States incidence of more than 150,000 cases per year. MPE is an aggressive disease with a uniformly fatal prognosis and a life expectancy of only 3 to 12  months. The development of an effective targeted therapy represents a pressing unmet need. This commentary focuses on how cellular and humoral components condition the pleural space as a tumor-promoting, wound-healing environment. Despite an abundance of potential antigen presenting and effector cells in the pleura, their physical isolation by the mesothel...
Source: Journal for Immunotherapy of Cancer - April 17, 2019 Category: Cancer & Oncology Source Type: research

Exploring the emerging role of the microbiome in cancer immunotherapy
AbstractThe activity of the commensal microbiota significantly impacts human health and has been linked to the development of many diseases, including cancer. Gnotobiotic animal models have shown that the microbiota has many effects on host physiology, including on the development and regulation of immune responses. More recently, evidence has indicated that the microbiota can more specifically influence the outcome of cancer immunotherapy. Therapeutic interventions to optimize microbiota composition to improve immunotherapy outcomes have shown promise in mouse studies. Ongoing endeavors are translating these pre-clinical ...
Source: Journal for Immunotherapy of Cancer - April 16, 2019 Category: Cancer & Oncology Source Type: research

Correction to: Infliximab associated with faster symptom resolution compared with corticosteroids alone for the management of immune-related enterocolitis
Following publication of the original article [1], the authors reported an error in their listed affiliations. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 16, 2019 Category: Cancer & Oncology Source Type: research

Checkpoint inhibitor therapy for cancer in solid organ transplantation recipients: an institutional experience and a systematic review of the literature
ConclusionsSOT recipients had a high allograft rejection rate that was observed shortly after CPI initiation, with high mortality rates. Further studies are needed to optimize the anticancer treatment approach in these patients. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 15, 2019 Category: Cancer & Oncology Source Type: research

Immunogenicity of immunomodulatory, antibody-based, oncology therapeutics
AbstractThe increasing use of multiple immunomodulatory (IMD) agents for cancer therapies (e.g. antibodies targeting immune checkpoints, bispecific antibodies, and chimeric antigen receptor [CAR]-T cells), is raising questions on their potential immunogenicity and effects on treatment. In this review, we outline the mechanisms of action (MOA) of approved, antibody-based IMD agents, potentially related to their immunogenicity, and discuss the reported incidence of anti-drug antibodies (ADA) as well as their clinical relevance in patients with cancer. In addition, we discuss the impact of the administration route and potenti...
Source: Journal for Immunotherapy of Cancer - April 14, 2019 Category: Cancer & Oncology Source Type: research