Journal for Immunotherapy of Cancer This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

CEA expression heterogeneity and plasticity confer resistance to the CEA-targeting bispecific immunotherapy antibody cibisatamab (CEA-TCB) in patient-derived colorectal cancer organoids
ConclusionsBased on these preclinical findings, heterogeneity and plasticity of CEA expression appear to confer low cibisatamab sensitivity in PDOs, supporting further clinical evaluation of their predictive effect in CRC. Pharmacological inhibition of the WNT/ β-catenin pathway may be a rational combination to sensitize CRCs to cibisatamab. Our novel PDO and T cell co-culture immunotherapy models enable pre-clinical discovery of candidate biomarkers and combination therapies that may inform and accelerate the development of immuno-oncology agents in the clinic. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 14, 2019 Category: Cancer & Oncology Source Type: research

The CTLA-4 x OX40 bispecific antibody ATOR-1015 induces anti-tumor effects through tumor-directed immune activation
ConclusionsBy targeting CTLA-4 and OX40 simultaneously, ATOR-1015 is directed to the tumor area where it induces enhanced immune activation, and thus has the potential to be a next generation CTLA-4 targeting therapy with improved clinical efficacy and reduced toxicity. ATOR-1015 is also expected to act synergistically with anti-PD-1/PD-L1 therapy. The pre-clinical data support clinical development of ATOR-1015, and a first-in-human trial has started (NCT03782467). (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 10, 2019 Category: Cancer & Oncology Source Type: research

Stereotactic radiosurgery combined with nivolumab or Ipilimumab for patients with melanoma brain metastases: evaluation of brain control and toxicity
ConclusionsConcurrent SRS and ipilimumab or nivolumab show meaningful intracranial activity in patients with either asymptomatic and symptomatic melanoma brain metastases, although a subset of patients may develop symptomatic RN. The combination of nivolumab with SRS is associated with better intracranial control. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 10, 2019 Category: Cancer & Oncology Source Type: research

Immune profiling of pre- and post-treatment breast cancer tissues from the SWOG S0800 neoadjuvant trial
ConclusionsActivated T cells in the tumor microenvironment are associated with pCR whereas stromal functions are associated with residual disease. Most immune functions decrease during neoadjuvant chemotherapy but several immunotherapy targets (PD-L1, IL6, IL8) remain expressed in RD suggesting potential therapeutic strategies. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 9, 2019 Category: Cancer & Oncology Source Type: research

Effective cancer immunotherapy by natural mouse conventional type-1 dendritic cells bearing dead tumor antigen
ConclusionsThis preclinical proof-of-principle study is first to support the therapeutic efficacy of cancer immunotherapy with syngeneic dead tumor cell antigen-loaded mouse cDC1s, the equivalents of the human dendritic cell subset that correlates with beneficial prognosis of cancer patients. Our data pave the way for translation of cDC1-based cancer treatments into the clinic when isolation of natural human cDC1s becomes feasible. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 7, 2019 Category: Cancer & Oncology Source Type: research

Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program
ConclusionsThe appearance of irAEs strongly correlates with survival benefit in a real-life population of mRCC pts treated with nivolumab. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 2, 2019 Category: Cancer & Oncology Source Type: research

Comparative analysis of the phase III clinical trials of anti-PD1 monotherapy in head and neck squamous cell carcinoma patients (CheckMate 141 and KEYNOTE 040)
AbstractTwo phase III clinical trials (CheckMate 141 and KEYNOTE 040) have independently demonstrated that overall survival (OS) in recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients, who have failed platinum-based therapy, can be improved with anti-PD1 monotherapy. Treatment with nivolumab or pembrolizumab in R/M HNSCC patients led to an improved OS with a hazards ratio (HR) of 0.70 (95%CI 0.51 –0.96;p = 0.01) and HR of 0.80 (95%CI 0.65–0.98,p = 0.0161), respectively, as compared to standard of care (SOC) chemo monotherapy regimens (specifically, cetuximab, docetaxel, or met...
Source: Journal for Immunotherapy of Cancer - April 2, 2019 Category: Cancer & Oncology Source Type: research

Severe cytokine release syndrome resulting in purpura fulminans despite successful response to nivolumab therapy in a patient with pleomorphic carcinoma of the lung: a case report
ConclusionThe severe systemic inflammatory reaction and impaired peripheral circulation in this patient was attributed to excessive immunological effect induced by nivolumab resulting in cytokine release syndrome (CRS). This is the first report of a patient with multiple pathological conditions including HLH, TTP-like condition, and PF presumably arising from ICI-induced CRS. Further accumulating thoroughly investigated cases would lead to better understanding of the disease and development of reliable cancer immunotherapy. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 2, 2019 Category: Cancer & Oncology Source Type: research

The correlations of tumor mutational burden among single-region tissue, multi-region tissues and blood in non-small cell lung cancer
AbstractHigh-level tissue tumor mutational burden (tTMB) or blood TMB (bTMB) are associated with better response of immunotherapy in non-small cell lung cancer (NSCLC) patients. However, the correlations of single-region tTMB, multi-region tTMB and bTMB remain to be determined. Moreover, whether intratumor heterogeneity (ITH) has impact on TMB should be clarified. We collected multi-region tumor tissues with matched blood from 32 operative NSCLC and evaluated single-region tTMB, multi-region tTMB and bTMB through a 1021-gene panel sequencing. TMB of>  9 mutations/Mb was classified as high. Besides, we used tTMB fold-c...
Source: Journal for Immunotherapy of Cancer - April 2, 2019 Category: Cancer & Oncology Source Type: research

Early introduction of selective immunosuppressive therapy associated with favorable clinical outcomes in patients with immune checkpoint inhibitor –induced colitis
ConclusionSIT should be introduced early in the disease course of IMC instead of waiting until failure of steroid therapy or steroid taper. Patients who received three or more infusions of SIT had more favorable clinical outcomes. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 1, 2019 Category: Cancer & Oncology Source Type: research

Could the menagerie of the gut microbiome really cure cancer? Hope or hype
AbstractThe investigational scale of the gut microbiome is expanding rapidly. In 2018, the intersection of gut microbiota and immuno-oncology received much attention. While the impact of gut microbiota on the immune system was already established, the year received an exponential expansion of microbiome ’s role in the immunotherapy setting. The microbiome research pipeline is ripe for large-scale, prospective trials. Working knowledge of immune-based cancer treatments, heterogeneity in their responses and resistance mechanisms, relevant immunological and microbiological pathways and potential for gut microbiome in enhanc...
Source: Journal for Immunotherapy of Cancer - April 1, 2019 Category: Cancer & Oncology Source Type: research

Determinant roles of dendritic cell-expressed Notch Delta-like and Jagged ligands on anti-tumor T  cell immunity
ConclusionOur data show the importance of specific expression of Notch ligands on DCs in the regulation of T-cell effector function. Thus, strategies incorporating selectively engineered Notch ligands could provide a novel approach of therapeutics for modulating immunity in various immunosuppressive conditions including cancer. (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 1, 2019 Category: Cancer & Oncology Source Type: research

Correction to: Therapeutic efficacy, pharmacokinetic profiles, and toxicological activities of humanized antibody-drug conjugate Zt/g4-MMAE targeting RON receptor tyrosine kinase for cancer therapy
Following publication of the original article [1], the author reported two errors in the authors affiliations: (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - April 1, 2019 Category: Cancer & Oncology Source Type: research

Complex inter-relationship of body mass index, gender and serum creatinine on survival: exploring the obesity paradox in melanoma patients treated with checkpoint inhibition
ConclusionsThe findings support the existence of an “obesity paradox” restricted to overweight/Class-I obesity in the real-world setting; the association was driven predominantly by males who largely had higher serum creatinine levels, a surrogate for skeletal muscle mass in the setting of metastatic disease. These observations suggest that sarco penia (low skeletal muscle mass) or direct measures of body mass composition may be more suitable predictors of survival in melanoma patients treated with PD-1 blockade (monotherapy/combination). (Source: Journal for Immunotherapy of Cancer)
Source: Journal for Immunotherapy of Cancer - March 28, 2019 Category: Cancer & Oncology Source Type: research

Interaction of host immunity with HER2-targeted treatment and tumor heterogeneity in HER2-positive breast cancer
AbstractGrowing evidence suggests a clear role of the host immune system in HER2+ breast cancer. In addition, HER2+ breast cancer is generally considered more immunogenic than hormone receptor-positive (HR+)/HER2-, and specific molecular HER2+ subgroups (e.g. HER2-enriched disease) are more immunogenic than others (e.g. Luminal A or B). From a clinical perspective, the immune system plays a relevant prognostic role in HER2+ breast cancer and contributes to the therapeutic effects of trastuzumab. However, as more HER2-targeted agents become available, a better understanding of the role played by the immune system in modulat...
Source: Journal for Immunotherapy of Cancer - March 28, 2019 Category: Cancer & Oncology Source Type: research