Identification of a naturally processed HLA-A*02:01-restricted CTL epitope from the human tumor-associated antigen Nectin-4
AbstractNectin-4 is a tumor antigen present on the surface of breast, ovarian and lung carcinoma cells. It is rarely present in normal adult tissues and is therefore a candidate target for cancer immunotherapy. Here, we identified a Nectin-4 antigenic peptide that is naturally presented to T cells by HLA-A2 molecules. We first screened the 502 nonamer peptides of Nectin-4 (510 amino acids) for binding to and off-rate from eight different HLA class I molecules. We then combined biochemical, cellular and algorithmic assays to select 5 Nectin-4 peptides that bound to HLA-A*02:01 molecules. Cytolytic T lymphocytes were obtaine...
Source: Cancer Immunology, Immunotherapy - August 11, 2016 Category: Cancer & Oncology Source Type: research

The HB22.7 –vcMMAE antibody–drug conjugate has efficacy against non-Hodgkin lymphoma mouse xenografts with minimal systemic toxicity
In this study, HB22.7, an anti-CD22 monoclonal antibody, was used for specific, targeted delivery of monomethyl auristatin E (MMAE) to non-Hodgkin lymphoma (NHL). MMAE was covalently coupled to HB22.7 through a valine –citrulline peptide linker (vc). Maleimide-functionalized vcMMAE (mal-vcMMAE) was reacted with thiols of the partially reduced mAb. Approximately 4 molecules of MMAE were conjugated to HB22.7 as determined by residual thiol measurement and hydrophobic interaction chromatography–HPLC (HIC-HPLC). HB22.7–vcMMAE antibody–drug conjugate (ADC) retained its binding to Ramos NHL cells and also...
Source: Cancer Immunology, Immunotherapy - August 9, 2016 Category: Cancer & Oncology Source Type: research

Inhibition of HIF-1 α enhances anti-tumor effects of dendritic cell-based vaccination in a mouse model of breast cancer
AbstractConsiderable evidence shows that the tumor microenvironment is an active participant in preventing immunosurveillance and limiting the efficacy of anticancer therapies. Hypoxia is a prominent characteristic of the solid tumor microenvironment. The transcription factor hypoxia-inducible factor-1 α (HIF-1α) is an important mediator of hypoxic response of tumor cells that modulates the expression of specific genes involved in tumor immunosuppression. Using a 4T1 breast cancer model, we show that in vivo administration of PX-478, an inhibitor of oxygen-sensitive HIF-1α, led to reduced expre ssion of F...
Source: Cancer Immunology, Immunotherapy - August 6, 2016 Category: Cancer & Oncology Source Type: research

Inhibition of mouse breast adenocarcinoma growth by ablation with intratumoral alpha-irradiation combined with inhibitors of immunosuppression and CpG
In this study, we investigated the anti-tumor potency of a treatment strategy, which combines DaRT tumor ablation with two approaches for the enhancement of anti-tumor reactivity: (1) neutralization of immunosuppressive cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) and (2) boost the immune response by the immunoadjuvant CpG. Mice bearing DA3 mammary adenocarcinoma with metastases were treated with DaRT wires in combination with a MDSC inhibitor (sildenafil), Treg inhibitor (cyclophosphamide at low dose), and the immunostimulant, CpG. Combination of all four therapies led to a complet...
Source: Cancer Immunology, Immunotherapy - August 6, 2016 Category: Cancer & Oncology Source Type: research

The immunomodulatory, antitumor and antimetastatic responses of melanoma-bearing normal and alcoholic mice to sunitinib and ALT-803: a combinatorial treatment approach
AbstractALT-803, a novel IL-15/IL-15 receptor alpha complex, and the tyrosine kinase inhibitor, sunitinib, were examined for their single and combined effects on the growth of subcutaneous B16BL6 melanoma and on lymph node and lung metastasis. The study was conducted in immunocompetent C57BL/6 mice drinking water (Water mice) and in mice that chronically consumed alcohol (Alcohol mice), which are deficient in CD8+ T cells. Sunitinib inhibited melanoma growth and was more effective in Alcohol mice. ALT-803 did not alter tumor growth or survival in Water or Alcohol mice. Combined ALT-803 and sunitinib inhibited melanoma grow...
Source: Cancer Immunology, Immunotherapy - August 1, 2016 Category: Cancer & Oncology Source Type: research

Reduced potency of cytotoxic T lymphocytes from patients with high-risk myelodysplastic syndromes
DiscussionAlthough phenotypically defined CTL numbers were increased in the bone marrow of MDS patients, we found that CTL from high-risk MDS patients exhibited a lower TCR-induced redirected cytotoxic capacity. Thus, decreased T cell cytotoxicity seems related to reduced adhesion to target cells and may contribute to impaired anti-leukemic immune surveillance in MDS. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - August 1, 2016 Category: Cancer & Oncology Source Type: research

Beta-glucan contamination of pharmaceutical products: How much should we accept?
Abstract Beta-glucans are large polysaccharides produced by a range of prokaryotic and eukaryotic organisms. They have potential immunostimulatory properties and have been used with therapeutic intent as anti-microbial and anti-tumour agents. A range of other potentially beneficial effects have been described, and oral forms of beta-glucans are widely available over-the-counter and online. Parenteral formulations are popular in parts of Asia and are the subject of ongoing trials, worldwide. Beta-glucans are also potential contaminants of pharmaceutical products, and high levels have been described in some blood products. ...
Source: Cancer Immunology, Immunotherapy - July 29, 2016 Category: Cancer & Oncology Source Type: research

Concepts in glioma immunotherapy
Abstract Immunotherapeutic concepts in neurooncology have been developed for many decades but have mainly been hampered by poor definition of relevant antigens and selective measures to target the central nervous system. Independent of the recent remarkable successes in clinical immunooncology with checkpoint inhibitors and vaccines, immunotherapy of brain tumors in general and gliomas in particular has evolved with novel neurooncology-specific concepts over the past years providing new phase 1 approaches of individualized immunotherapy to first phase three clinical trials. These concepts are driven by a high medical need...
Source: Cancer Immunology, Immunotherapy - July 26, 2016 Category: Cancer & Oncology Source Type: research

Effector T cell subclasses associate with tumor burden in neurofibromatosis type 1 patients
Abstract Neurofibromatosis type 1 (NF1) is a hereditary tumor syndrome caused by mutations of the NF1 gene and resulting dysregulation of the Ras-pathway. In addition to peripheral nerve tumors, affected tissues include the musculoskeletal and cardiovascular system. The immune system has recently been suggested as a possible modulator NF1-related phenotypes. Therefore, we determined the immune phenotype in NF1 patients and investigated its relationship with the phenotypic severity of NF1-related tumor manifestations. We quantified global leukocytes and lymphocyte subpopulations of peripheral blood from 37 NF1 patients an...
Source: Cancer Immunology, Immunotherapy - July 23, 2016 Category: Cancer & Oncology Source Type: research

Lung adenocarcinoma may be a more susceptive subtype to a dendritic cell-based cancer vaccine than other subtypes of non-small cell lung cancers: a multicenter retrospective analysis
Conclusions This is the first multicenter study that suggests a possible clinical benefit of DC vaccines for patients with advanced NSCLC, especially those with adenocarcinoma. These findings suggest a specific potential responder population for DC vaccines and warrant further investigation in well-controlled prospective randomized trials. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - July 22, 2016 Category: Cancer & Oncology Source Type: research

Resistance to cytotoxicity and sustained release of interleukin-6 and interleukin-8 in the presence of decreased interferon- γ after differentiation of glioblastoma by human natural killer cells
Abstract Natural killer (NK) cells are functionally suppressed in the glioblastoma multiforme (GBM) tumor microenvironment. We have recently shown that survival and differentiation of cancer stem-like cells (CSCs)/poorly differentiated tumors are controlled through two distinct phenotypes of cytotoxic and non-cytotoxic/split anergized NK cells, respectively. In this paper, we studied the function of NK cells against brain CSCs/poorly differentiated GBM and their NK cell-differentiated counterparts. Brain CSCs/poorly differentiated GBM, differentiated by split anergized NK supernatants (supernatants from NK cells treated w...
Source: Cancer Immunology, Immunotherapy - July 20, 2016 Category: Cancer & Oncology Source Type: research

Uptake of synthetic naked RNA by skin-resident dendritic cells via macropinocytosis allows antigen expression and induction of T-cell responses in mice
This report demonstrates that direct antigen translation by dermal DCs after intradermal naked RNA vaccination is relevant for efficient priming of antigen-specific T-cells. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - July 15, 2016 Category: Cancer & Oncology Source Type: research

DNA methyltransferase inhibition increases efficacy of adoptive cellular immunotherapy of murine breast cancer
In this study, we have investigated the effect of combining the DNAMTi, decitabine, with adoptive T cell immunotherapy in the murine 4T1 mammary carcinoma model. We found that expression of neu, MHC class I molecules, and several murine cancer testis antigens (CTA) was increased by decitabine treatment of 4T1 cells in vitro. Decitabine also increased expression of multiple CTA in two human breast cancer cell lines. Decitabine-treated 4T1 cells stimulated greater IFN-gamma release from tumor-sensitized lymphocytes, implying increased immunogenicity. Expansion of CD11b + Gr1 + MDSC in 4T1 tumor-bearing mi...
Source: Cancer Immunology, Immunotherapy - July 14, 2016 Category: Cancer & Oncology Source Type: research

Human NK cells maintain licensing status and are subject to killer immunoglobulin-like receptor (KIR) and KIR-ligand inhibition following ex vivo expansion
Abstract Infusion of allogeneic NK cells is a potential immunotherapy for both hematopoietic malignancies and solid tumors. Interactions between killer immunoglobulin-like receptors (KIR) on human NK cells and KIR-ligands on tumor cells influence the magnitude of NK function. To obtain sufficient numbers of activated NK cells for infusion, one potent method uses cells from the K562 human erythroleukemia line that have been transfected to express activating 41BB ligand (41BBL) and membrane-bound interleukin 15 (mbIL15). The functional importance of KIRs on ex vivo expanded NK cells has not been studied in detail. W...
Source: Cancer Immunology, Immunotherapy - July 8, 2016 Category: Cancer & Oncology Source Type: research

B7-H4 expression indicates poor prognosis of oral squamous cell carcinoma
In this study, tissue samples from human OSCC, which contains 165 primary OSCC, 48 oral epithelial dysplasia and 43 normal oral mucosa specimens, and Tgfbr1/Pten 2cKO mice OSCC model were stained with B7-H4 antibody to analyze the correlations between B7-H4 expression and clinicopathological characteristics. Kaplan–Meier analysis was used to compare the survival of patients with high B7-H4 expression and patients with low B7-H4 expression. We found B7-H4 is highly expressed in human OSCC tissue, and the B7-H4 expression level was associated with the clinicopathological parameters containing pathological grade and lym...
Source: Cancer Immunology, Immunotherapy - July 6, 2016 Category: Cancer & Oncology Source Type: research

Enhanced binding of necrosis-targeting immunocytokine NHS-IL12 after local tumour irradiation in murine xenograft models
Conclusions In dependence of the tumour model, tumour irradiation enhanced tumour necrosis measured in MRI and histology. In vivo PET and ex vivo biodistribution showed enhanced binding of NHS-IL12 in rhabdomyosarcoma xenografts. Thus, enhanced binding of necrosis-targeting immunocytokines might be a novel mechanism of additive effects in combination with irradiation. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - July 4, 2016 Category: Cancer & Oncology Source Type: research

Systematic review of the use of granulocyte –macrophage colony-stimulating factor in patients with advanced melanoma
Abstract Several immunomodulatory checkpoint inhibitors have been approved for the treatment of patients with advanced melanoma, including ipilimumab, nivolumab and pembrolizumab. Talimogene laherparepvec is the first oncolytic virus to gain regulatory approval in the USA; it is also approved in Europe. Talimogene laherparepvec expresses granulocyte –macrophage colony-stimulating factor (GM-CSF), and with other GM-CSF-expressing oncolytic viruses in development, understanding the clinical relevance of this cytokine in treating advanced melanoma is important. Results of trials of GM-CSF in melanoma have been mixe...
Source: Cancer Immunology, Immunotherapy - July 2, 2016 Category: Cancer & Oncology Source Type: research

Systematic review of the use of granulocyte–macrophage colony-stimulating factor in patients with advanced melanoma
Abstract Several immunomodulatory checkpoint inhibitors have been approved for the treatment of patients with advanced melanoma, including ipilimumab, nivolumab and pembrolizumab. Talimogene laherparepvec is the first oncolytic virus to gain regulatory approval in the USA; it is also approved in Europe. Talimogene laherparepvec expresses granulocyte–macrophage colony-stimulating factor (GM-CSF), and with other GM-CSF-expressing oncolytic viruses in development, understanding the clinical relevance of this cytokine in treating advanced melanoma is important. Results of trials of GM-CSF in melanoma have be...
Source: Cancer Immunology, Immunotherapy - July 2, 2016 Category: Cancer & Oncology Source Type: research

Expression of CCL21 in Ewing sarcoma shows an inverse correlation with metastases and is a candidate target for immunotherapy
Abstract Ewing sarcoma is an aggressive neoplasm predominantly occurring in adolescents and has a poor prognosis when metastasized. For patients with metastatic disease in particular, immunotherapy has been proposed as possible beneficial additive therapy. CCL21 activation-based immunotherapy was successful in preclinical studies in other tumor types; therefore, we investigated CCL21 expression in Ewing sarcoma as potential target for immunotherapy. The CCL21 RNA expression was determined in 21 Ewing sarcoma cell lines and 18 primary therapy-naive Ewing sarcoma samples. In the tumor samples, this was correlated wi...
Source: Cancer Immunology, Immunotherapy - July 1, 2016 Category: Cancer & Oncology Source Type: research

Modulation of innate immunity in the tumor microenvironment
Abstract A recent report from the Center for Disease Control identified melanoma as being among the highest causes of cancer-related mortalities in the USA. While interventions such as checkpoint blockade have made substantial impact in terms of improving response rates and overall survival, a significant number of patients fail to respond to treatment or become resistant to therapy. A better understanding of the tumor microenvironment in these patients becomes imperative for identifying immune suppressive mechanisms that impact the development of effective anti-tumor immune responses. We have investigated innate ...
Source: Cancer Immunology, Immunotherapy - June 25, 2016 Category: Cancer & Oncology Source Type: research

Circulating immune cell phenotype can predict the outcome of lenalidomide plus low-dose dexamethasone treatment in patients with refractory/relapsed multiple myeloma
In this study, we analyzed the association between immune cell populations and clinical outcomes in patients receiving Len-dex for the treatment of RRMM. Peripheral blood samples from 90 RRMM patients were taken on day 1 of cycles 1 (baseline), 2, 3, and 4 of Len-dex therapy. Peripheral blood CD3+, CD4+, and CD8+ cell frequencies were significantly decreased by 3 cycles of therapy, whereas NK cell frequency was significantly increased after the 3rd cycle. For the myeloid-derived suppressor cell (MDSC) subset, the frequency of granulocytic MDSCs transiently increased after the 1st cycle, whereas there was an increase in mon...
Source: Cancer Immunology, Immunotherapy - June 24, 2016 Category: Cancer & Oncology Source Type: research

Age-associated impairment of antitumor immunity in carcinoma-bearing mice and restoration by oral administration of Lentinula edodes mycelia extract
In this study, we investigated antitumor immunity in aged mice using a CT26 colon carcinoma model. The tumor growth of CT26 was accelerated in aged mice compared with that in young mice, but this difference was not observed in nude mice. The serum levels of IL-6 and TNF-α were higher in aged mice than those in young mice, irrespective of the CT26-bearing state. The in vitro induction of CT26-specific CTLs from aged mice that were vaccinated with doxorubicin (DTX)-treated CT26 cells was impaired. In vivo neutralization of IL-6, but not TNF-α, showed a tendency to restore the in vitro induction of CT26-specific C...
Source: Cancer Immunology, Immunotherapy - June 16, 2016 Category: Cancer & Oncology Source Type: research

Optimized magnitude of cryosurgery facilitating anti-tumor immunoreaction in a mouse model of Lewis lung cancer
Conclusions This study suggested that achievement of approximately 73 % damaged area in the cryoablated tumor by two cycles of cryosurgery generates the most favorable immune-regulatory response for abscopal tumors via activation of anti-tumor immune cells as well as increased secretion of proinflammatory cytokines. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - June 16, 2016 Category: Cancer & Oncology Source Type: research

Immune checkpoint blockade with concurrent electrochemotherapy in advanced melanoma: a retrospective multicenter analysis
Abstract Growing evidence suggests that concurrent loco-regional and systemic treatment modalities may lead to synergistic anti-tumor effects in advanced melanoma. In this retrospective multicenter study, we evaluate the use of electrochemotherapy (ECT) combined with ipilimumab or PD-1 inhibition. We investigated patients with unresectable or metastatic melanoma who received the combination of ECT and immune checkpoint blockade for distant or cutaneous metastases within 4 weeks. Clinical and laboratory data were collected and analyzed with respect to safety and efficacy. A total of 33 patients from 13 centers...
Source: Cancer Immunology, Immunotherapy - June 13, 2016 Category: Cancer & Oncology Source Type: research

Using natural products to promote caspase-8-dependent cancer cell death
Abstract The selective killing of cancer cells without toxicity to normal nontransformed cells is an idealized goal of cancer therapy. Thus, there has been much interest in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a protein that appears to selectively kill cancer cells. TRAIL has been reported to trigger apoptosis and under some circumstances, an alternate death signaling pathway termed necroptosis. The relative importance of necroptosis for cell death induction in vivo is under intensive investigation. Nonetheless, many cancer cells (particularly those freshly isolated from cancer patient...
Source: Cancer Immunology, Immunotherapy - June 10, 2016 Category: Cancer & Oncology Source Type: research

Extension of overall survival beyond objective responses in patients with metastatic renal cell carcinoma treated with high-dose interleukin-2
Abstract Purpose In metastatic renal cell carcinoma (mRCC), survival benefit associated with objective response rates of 16–20 % with high-dose interleukin-2 (HDIL-2) is well established and discussed. Based on recently emerged data on efficacy of cancer immunotherapy, we hypothesized that the survival benefit with HDIL-2 extends beyond those achieving objective responses, i.e., to those who achieve stable disease as the best response to treatment. Materials and methods All sequential treatment naïve mRCC patients treated with HDIL-2 at ...
Source: Cancer Immunology, Immunotherapy - June 8, 2016 Category: Cancer & Oncology Source Type: research

Uncoupling protein 2 regulates metabolic reprogramming and fate of antigen-stimulated CD8+ T cells
Abstract Adoptive cell therapy (ACT) employing ex vivo-generated tumor antigen-specific CD8+ T cells shows tumor efficacy when the transferred cells possess both effector and memory functions. New strategies based on understanding of mechanisms that balance CD8+ T cell differentiation toward effector and memory responses are highly desirable. Emerging information confirms a central role for antigen-induced metabolic reprogramming in CD8+ T cell differentiation and clonal expansion. The mitochondrial protein uncoupling protein 2 (UCP2) is induced by antigen stimulation of CD8+ T cells; however, its role in metaboli...
Source: Cancer Immunology, Immunotherapy - June 6, 2016 Category: Cancer & Oncology Source Type: research

Immunoglobulin G4 (IgG4)-positive plasma cell infiltration is associated with the clinicopathologic traits and prognosis of pancreatic cancer after curative resection
In conclusion, IgG4-positive plasma cell infiltration is correlated with the clinicopathologic traits and overall survival of pancreatic cancer. High-level intratumoral infiltration of IgG4-positive plasma cells is an independent predictor for poor overall survival in pancreatic cancer patients after curative resection. Intratumoral M2-polarized TAMs probably induce IgG4-positive plasma cells. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - June 6, 2016 Category: Cancer & Oncology Source Type: research

Immunotherapy after hematopoietic stem cell transplantation using umbilical cord blood-derived products
Abstract Umbilical cord blood (UCB) is being increasingly used as a source of hematopoietic stem cells (HSC) for transplantation. UCB transplantation (UCBT) has some advantages such as less stringent HLA-matching requirements, fast availability of the graft and reduced incidence and severity of graft-versus-host disease. However, UCBT is also associated with a higher incidence of infection, graft failure, slow engraftment and slow immune reconstitution. UCB is mainly used as a source of HSC; however, it is also rich in immune cells that could be used to treat some of the main complications post-UCBT as well as oth...
Source: Cancer Immunology, Immunotherapy - June 6, 2016 Category: Cancer & Oncology Source Type: research

Regulation of CD40 signaling in colon cancer cells and its implications in clinical tissues
Abstract CD40 is a member of the tumor necrosis factor receptor family. We reveal here a correlation between CD40 expression and colon cancer differentiation. Upon CD40 ligand (CD40L) binding, CD40/CD40L signaling inhibited colon cancer proliferation, induced apoptosis, stalled cells at G0/G1, and influenced cell adhesion and metastasis. Clustering analysis identified the elevation of aryl hydrocarbon receptor repressor (AHRR) expression along with activation of CD40/CD40L signaling. Examination of clinical specimens revealed that both AHR and AHRR levels correlated with colon cancer histological grade. In additio...
Source: Cancer Immunology, Immunotherapy - June 4, 2016 Category: Cancer & Oncology Source Type: research

The right patient for the right therapy: 13th Annual Meeting of the Association for Cancer Immunotherapy (CIMT), Mainz, Germany, May 11–13, 2015
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - June 3, 2016 Category: Cancer & Oncology Source Type: research

Myeloid-derived suppressor cells as intruders and targets: clinical implications in cancer therapy
Abstract Chronic inflammation, typical of various diseases including cancer, is a “silent bomb within the body,” leading to complications that are only evident in most cases upon their appearance, when disease is already deteriorated. Chronic inflammation is associated with accumulation of myeloid-derived suppressor cells (MDSCs), which lead to immunosuppression. MDSCs have numerous harmful effects as they support tumor initiation, tumor growth and spreading, which in turn, perpetuate the inflammatory and suppressive conditions, thus preventing anticancer responses. As the concept of the immune sys...
Source: Cancer Immunology, Immunotherapy - May 25, 2016 Category: Cancer & Oncology Source Type: research

Pro- and anti-tumour effects of B cells and antibodies in cancer: a comparison of clinical studies and preclinical models
Abstract The primary immune role of B cells is to produce antibodies, but they can also influence T cell function via antigen presentation and, in some contexts, immune regulation. Whether their roles in tumour immunity are similar to those in other chronic immune responses such as autoimmunity and chronic infection, where both pro- and anti-inflammatory roles have been described, remains controversial. Many studies have aimed to define the role of B cells in antitumor immune responses, but despite this considerable body of work, it is not yet possible to predict how they will affect immunity to any given tumour. ...
Source: Cancer Immunology, Immunotherapy - May 24, 2016 Category: Cancer & Oncology Source Type: research

CTLA-4 in mesothelioma patients: tissue expression, body fluid levels and possible relevance as a prognostic factor
Abstract CTLA-4 function as a negative regulator of T cell-mediated immune response is well established, whereas much less is known about the immunoregulatory role of its soluble isoform (sCTLA-4). No data are available on CTLA-4 expression and prognostic impact in malignant pleural mesothelioma (MPM). We investigated, by immunohistochemistry, CTLA-4 expression in tumor tissues and, by ELISA, sCTLA-4 levels in sera and matched pleural effusions from 45 MPM patients. Prognostic effect of CTLA-4 expression on overall survival (OS) was assessed through Cox regression and prognostic significance expressed as death rat...
Source: Cancer Immunology, Immunotherapy - May 20, 2016 Category: Cancer & Oncology Source Type: research

Phase I study to evaluate toxicity and feasibility of intratumoral injection of α-gal glycolipids in patients with advanced melanoma
Abstract Effective uptake of tumor cell-derived antigens by antigen-presenting cells is achieved pre-clinically by in situ labeling of tumor with α-gal glycolipids that bind the naturally occurring anti-Gal antibody. We evaluated toxicity and feasibility of intratumoral injections of α-gal glycolipids as an autologous tumor antigen-targeted immunotherapy in melanoma patients (pts). Pts with unresectable metastatic melanoma, at least one cutaneous, subcutaneous, or palpable lymph node metastasis, and serum anti-Gal titer ≥1:50 were eligible for two intratumoral α-gal glycolipid injections given...
Source: Cancer Immunology, Immunotherapy - May 20, 2016 Category: Cancer & Oncology Source Type: research

Determining predictive factors for immune checkpoint inhibitor toxicity: Response to Letter to the Editors “A case report of insulin-dependent diabetes as immune-related toxicity of pembrolizumab: presentation, management and outcome”
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - May 19, 2016 Category: Cancer & Oncology Source Type: research

Concomitant targeting of programmed death-1 (PD-1) and CD137 improves the efficacy of radiotherapy in a mouse model of human BRAFV600-mutant melanoma
Abstract T cell checkpoint blockade with antibodies targeting programmed cell death (ligand)-1 (PD-1/PD-L1) and/or cytotoxic T lymphocyte-antigen 4 (CTLA-4) has improved therapy outcome in melanoma patients. However, a considerable proportion of patients does not benefit even from combined α-CTLA-4 and α-PD-1 therapy. We therefore examined to which extent T cell (co)stimulation and/or stereotactic body radiation therapy (SBRT) could further enhance the therapeutic efficacy of T cell checkpoint blockade in a genetically engineered mouse melanoma model that is driven by PTEN-deficiency, and BRAFV600 mut...
Source: Cancer Immunology, Immunotherapy - May 9, 2016 Category: Cancer & Oncology Source Type: research

Strategies to genetically engineer T cells for cancer immunotherapy
Abstract Immunotherapy is one of the most promising and innovative approaches to treat cancer, viral infections, and other immune-modulated diseases. Adoptive immunotherapy using gene-modified T cells is an exciting and rapidly evolving field. Exploiting knowledge of basic T cell biology and immune cell receptor function has fostered innovative approaches to modify immune cell function. Highly translatable clinical technologies have been developed to redirect T cell specificity by introducing designed receptors. The ability to engineer T cells to manifest desired phenotypes and functions is now a thrilling reality...
Source: Cancer Immunology, Immunotherapy - May 2, 2016 Category: Cancer & Oncology Source Type: research

Neutrophil elastase enhances antigen presentation by upregulating human leukocyte antigen class I expression on tumor cells
In this study, we extend these observations to show that NE uptake has a broad effect on enhancing antigen presentation by breast cancer cells. We show that NE increases human leukocyte antigen (HLA) class I expression on the surface of breast cancer cells in a concentration and time-dependent manner. HLA class I upregulation requires internalization of enzymatically active NE. Western blots of NE-treated breast cancer cells confirm that the expression of total HLA class I as well as the antigen-processing machinery proteins TAP1, LMP2, and calnexin does not change following NE treatment. This suggests that NE does not inc...
Source: Cancer Immunology, Immunotherapy - April 29, 2016 Category: Cancer & Oncology Source Type: research

How frequently are predicted peptides actually recognized by CD8 cells?
Abstract Detection of antigen-specific CD8 cells frequently relies on the use of peptides that are predicted to bind to HLA Class I molecules or have been shown to induce immune responses. There is extensive knowledge on individual HLA alleles’ peptide-binding requirements, and immunogenic peptides for many antigens have been defined. The 32 individual peptides that comprise the CEF peptide pool represent such well-defined peptide determinants for Cytomegalo-, Epstein–barr-, and Influenza virus. We tested the accuracy of these peptide recognition predictions on 42 healthy human donors that have been hi...
Source: Cancer Immunology, Immunotherapy - April 23, 2016 Category: Cancer & Oncology Source Type: research

Immunobiology and immunosurveillance in patients with intraductal papillary mucinous neoplasms (IPMNs), premalignant precursors of pancreatic adenocarcinomas
Abstract Premalignant lesions for many cancers have been identified, and efforts are currently directed toward identification of antigens expressed on these lesions that would provide suitable targets for vaccines for cancer prevention. Intraductal papillary mucinous neoplasms (IPMNs) are premalignant pancreatic cysts of which a subset has the potential to progress to cancer. Currently, there are no validated predictive markers for progression to malignancy. We hypothesized that the presence or absence of immune surveillance of these lesions would be one such factor. Here we show that the tumor antigen MUC1, whic...
Source: Cancer Immunology, Immunotherapy - April 22, 2016 Category: Cancer & Oncology Source Type: research

Disease progression in recurrent glioblastoma patients treated with the VEGFR inhibitor axitinib is associated with increased regulatory T cell numbers and T cell exhaustion
Conclusion Our results suggest that axitinib treatment in patients with recurrent glioblastoma has a favorable impact on immune function. At the time of acquired resistance to axitinib, we documented further enhancement of a preexisting immunosuppression. Further investigations on the role of axitinib as potential combination partner with immunotherapy are necessary. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 20, 2016 Category: Cancer & Oncology Source Type: research

Myeloid-derived suppressor cells correlate with patient outcomes in hepatic arterial infusion chemotherapy for hepatocellular carcinoma
In this study, we performed a comparative analysis of various immune cell responses including tumor-associated antigen (TAA)-specific T cells, regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in advanced HCC patients treated with HAIC. Thirty-six HCC patients were examined in the study. Interferon gamma enzyme-linked immunospot assays were performed to examine the frequency of TAA-specific T cells. The frequencies of Tregs and MDSCs were examined by multicolor fluorescence-activated cell sorting analysis. The treatment with HAIC using interferon (IFN)/5-fluorouracil (FU) or IFN/FU + cisplat...
Source: Cancer Immunology, Immunotherapy - April 15, 2016 Category: Cancer & Oncology Source Type: research

A case report of insulin-dependent diabetes as immune-related toxicity of pembrolizumab: presentation, management and outcome
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 11, 2016 Category: Cancer & Oncology Source Type: research

Opportunities for immunotherapy in microsatellite instable colorectal cancer
Abstract Microsatellite instability (MSI), the somatic accumulation of length variations in repetitive DNA sequences called microsatellites, is frequently observed in both hereditary and sporadic colorectal cancer (CRC). It has been established that defects in the DNA mismatch repair (MMR) pathway underlie the development of MSI in CRC. After the inactivation of the DNA MMR pathway, misincorporations, insertions and deletions introduced by DNA polymerase slippage are not properly recognized and corrected. Specific genomic regions, including microsatellites, are more prone for DNA polymerase slippage and, therefore...
Source: Cancer Immunology, Immunotherapy - April 8, 2016 Category: Cancer & Oncology Source Type: research

“Tumor immunology meets oncology” (TIMO) XI, May 22–23, 2015, Halle/Saale, Germany
(Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - April 8, 2016 Category: Cancer & Oncology Source Type: research

Designing therapeutic cancer vaccines by mimicking viral infections
Abstract The design of efficacious and cost-effective therapeutic vaccines against cancer remains both a research priority and a challenge. For more than a decade, our laboratory has been involved in the development of synthetic peptide-based anti-cancer therapeutic vaccines. We first dedicated our efforts in the identification and validation of peptide epitopes for both CD8 and CD4 T cells from tumor-associated antigens (TAAs). Because of suboptimal immune responses and lack of therapeutic benefit of peptide vaccines containing these epitopes, we have focused our recent efforts in optimizing peptide vaccinations ...
Source: Cancer Immunology, Immunotherapy - April 6, 2016 Category: Cancer & Oncology Source Type: research

Immunogenicity and efficacy of the novel cancer vaccine based on simian adenovirus and MVA vectors alone and in combination with PD-1 mAb in a mouse model of prostate cancer
Abstract Prostate cancer possesses several characteristics that make it a suitable candidate for immunotherapy; however, prostate cancer vaccines to date demonstrate modest efficacy and low immunogenicity. The goal of the present pre-clinical study was to explore the immunogenic properties and protective efficacy of a novel prostate cancer immunotherapy based on the heterologous prime–boost viral-vectored vaccination platform. The simian adenovirus, ChAdOx1, and modified vaccinia Ankara virus, MVA, encoding a prostate cancer-associated antigen, the six transmembrane epithelial antigen of the prostate 1 (STEA...
Source: Cancer Immunology, Immunotherapy - April 6, 2016 Category: Cancer & Oncology Source Type: research

Differential immunomodulatory activity of tumor cell death induced by cancer therapeutic toll-like receptor ligands
In this study we investigated immunological events associated with the induction of tumor cell death by poly(I:C) and imiquimod. A human head and neck squamous cell carcinoma (HNSCC) cell line was exposed to poly(I:C) and imiquimod, which were delivered exogenously via culture medium or via electroporation. Cell death and cell biological consequences thereof were analyzed. For in vivo analyses, a human xenograft and a syngeneic immunocompetent mouse model were used. Poly(I:C) induced cell death only if delivered by electroporation into the cytosol. Cell death induced by poly(I:C) resulted in cytokine release and activation...
Source: Cancer Immunology, Immunotherapy - March 31, 2016 Category: Cancer & Oncology Source Type: research

Adoptive transfer of osteoclast-expanded natural killer cells for immunotherapy targeting cancer stem-like cells in humanized mice
Abstract Based on data obtained from oral, pancreatic and lung cancers, glioblastoma, and melanoma, we have established that natural killer (NK) cells target cancer stem-like cells (CSCs). CSCs displaying low MHC class I, CD54, and PD-L1 are killed by cytotoxic NK cells and are differentiated by split anergized NK cells through both membrane bound and secreted forms of TNF-α and IFN-γ. NK cells select and differentiate both healthy and transformed stem-like cells, resulting in target cell maturation and shaping of their microenvironment. In our recent studies, we have observed that oral, pancreatic, an...
Source: Cancer Immunology, Immunotherapy - March 31, 2016 Category: Cancer & Oncology Source Type: research