MAGE-A4 pMHC-targeted CAR-T cells exploiting TCR machinery exhibit significantly improved in vivo function while retaining antigen specificity.

Background: The development of chimeric antigen receptor (CAR)-T cell therapies for solid tumors has attracted considerable attention, yet their clinical efficacy remains limited. Therefore, various efforts have been made to improve the efficacy of CAR-T cell therapy. As one promising strategy, incorporating the T-cell receptor (TCR) machinery into CAR structures has been reported to improve the efficacy of CAR-T cells in studies using conventional CARs targeting such as EGFR.

Immunological landscape of human lymphoid explants during measles virus infection.

In humans, lymph nodes are the primary site of measles virus (MeV) replication. To understand the immunological events that occur at this site, we infected human lymphoid tissue explants using a pathogenic strain of MeV that expresses GFP. We found that MeV infected 5%-15% of cells across donors.

Antitumor immunity as the basis for durable disease-free treatment-free survival in patients with metastatic urothelial cancer.

Cisplatin-based chemotherapy has been associated with durable disease control in a small subset of patients with metastatic urothelial cancer. However, the mechanistic basis for this phenomenon has remained elusive. Antitumor immunity may underlie these exceptional responders.

CD226 and TIGIT Cooperate in the Differentiation and Maturation of Human Tfh Cells.

Costimulation pathways play an essential role in T cell activation, differentiation, and regulation. CD155 expressed on antigen-presenting cells (APCs) interacts with TIGIT, an inhibitory costimulatory molecule, and CD226, an activating costimulatory molecule, on T cells. TIGIT and CD226 are expressed at varying levels depending on the T cell subset and activation state.

CD4 T cells support polyfunctionality of cytotoxic CD8 T cells with memory potential in immunological control of tumor.

Polyfunctionality/multifunctionality of effector T cells at the single cell level has been shown as an important parameter to predict the quality of T cell response and immunological control of infectious disease and malignancy. However, the fate of polyfunctional CD8 CTLs and the factors that control the polyfunctionality of T cells remain largely unknown. Here we show that the acquisition of polyfunctionality on the initial stimulation is a sensitive immune correlate of CTL survival and memory formation.

Mutation-derived Neoantigen-specific T-cell Responses in Multiple Myeloma.

Purpose: Somatic mutations in cancer cells can give rise to novel protein sequences that can be presented by antigen-presenting cells as neoantigens to the host immune system. Tumor neoantigens represent excellent targets for immunotherapy, due to their specific expression in cancer tissue. Despite the widespread use of immunomodulatory drugs and immunotherapies that recharge T and NK cells, there has been no direct evidence that neoantigen-specific T-cell responses are elicited in multiple myeloma.

Autologous Lymphocyte Infusion Supports Tumor Antigen Vaccine-Induced Immunity in Autologous Stem Cell Transplant for Multiple Myeloma.

Autologous stem cell transplant (autoSCT), the standard consolidation therapy for multiple myeloma, improves disease-free survival, but is not curative. This could be an ideal setting for immunologic therapy. However, the immune milieu is impaired after autoSCT.

Radiotherapy induces responses of lung cancer to CTLA-4 blockade.

Focal radiation therapy enhances systemic responses to anti-CTLA-4 antibodies in preclinical studies and in some patients with melanoma, but its efficacy in inducing systemic responses (abscopal responses) against tumors unresponsive to CTLA-4 blockade remained uncertain. Radiation therapy promotes the activation of anti-tumor T cells, an effect dependent on type I interferon induction in the irradiated tumor. The latter is essential for achieving abscopal responses in murine cancers.

Immunohistochemical Detection of γ/δ T Lymphocytes in Formalin-fixed Paraffin-embedded Tissues.

T lymphocytes can be distinguished based on the composition of the T-cell receptor (TCR) chain in α/β T cells and γ/δ T cells. Correspondingly, α/β lymphomas can be distinguished from γ/δ lymphomas. The latter are rare neoplasms, which are usually confined to particular organs and tissues and carry a dismal prognosis.

Changes in peripheral blood T-cell balance after percutaneous tumor ablation.

Purpose: To evaluate the changes in T-cell balance in peripheral blood following percutaneous tumor ablation.

Material And Methods: Patients underwent thermal ablation including radiofrequency (n = 9) and microwave ablation (n = 5), or cryoablation (n = 5). Target tumors were located in the lung (n = 7), soft tissue (n = 5), liver (n = 4), and bone (n = 3).

IFN-γ is required for cytotoxic T cell-dependent cancer genome immunoediting.

Genetic evolution that occurs during cancer progression enables tumour heterogeneity, thereby fostering tumour adaptation, therapeutic resistance and metastatic potential. Immune responses are known to select (immunoedit) tumour cells displaying immunoevasive properties. Here we address the role of IFN-γ in mediating the immunoediting process.

Time-dependent transition of the immunoglobulin G subclass and immunoglobulin E response in cancer patients vaccinated with cholesteryl pullulan-melanoma antigen gene-A4 nanogel.

A phase I+II clinical trial of vaccination with MAGE-A4 protein complexed with cholesteryl pullulan melanoma antigen gene-A4 nanogel (CHP-MAGE-A4) is currently underway in patients with MAGE-A4-expressing cancer. In the present study, the primary phase I endpoint was to test the safety of the administration of 300 µg CHP-MAGE-A4 with and without OK-432. Another aim of the study was to clarify the details of the specific humoral immune response to vaccination.

Differential detection of cytoplasmic Wilms tumor 1 expression by immunohistochemistry, western blotting and mRNA quantification.

Wilms tumor 1 (WT1) is considered to be a promising target of cancer treatment because it has been reported to be frequently expressed at high levels in various malignancies. Although WT1-targeted cancer treatment has been initiated, conclusive detection methods for WT1 are not established. The present study aimed to consolidate immunohistochemistry for WT1 with statistical basis.

Melanoma and immunotherapy bridge 2015 : Naples, Italy. 1-5 December 2015.

MELANOMA BRIDGE 2015 KEYNOTE SPEAKER PRESENTATIONS Molecular and immuno-advances K1 Immunologic and metabolic consequences of PI3K/AKT/mTOR activation in melanoma Vashisht G. Y. Nanda, Weiyi Peng, Patrick Hwu, Michael A.

Peripheral Blood Regulatory T-Cell and Type 1 Helper T-Cell Population Decrease after Hepatic Artery Embolization.

Purpose: To evaluate changes in T-cell populations in peripheral blood after bland hepatic artery embolization (HAE).

Materials And Methods: Bland HAE was performed in 12 patients to treat primary (n = 5) or metastatic (n = 7) liver tumors, using microspheres and polyvinyl alcohol (n = 8) or microspheres alone (n = 4). Patient peripheral blood samples were collected within 1 month before HAE, within 1 week after HAE (early period after HAE), and 2-8 weeks after HAE (follow-up period).

Chemoradiotherapy-induced upregulation of PD-1 antagonizes immunity to HPV-related oropharyngeal cancer.

While viral antigens in human papillomavirus (HPV)-related oropharyngeal cancer (HPVOPC) are attractive targets for immunotherapy, the effects of existing standard-of-care therapies on immune responses to HPV are poorly understood. We serially sampled blood from patients with stage III-IV oropharyngeal cancer undergoing concomitant chemoradiotherapy with or without induction chemotherapy. Circulating immunocytes including CD4(+) and CD8(+) T cells, regulatory T cells (Treg), and myeloid-derived suppressor cells (MDSC) were profiled by flow cytometry.

Stimulation through very late antigen-4 and -5 improves the multifunctionality and memory formation of CD8⁺ T cells.

T cells express multiple integrin molecules. The significance of signaling through these molecules on acquisition of T-cell effector functions and memory formation capacity remains largely unknown. Moreover, the impact of stimulation through these signals on the generation of T cells for adoptive immunotherapy has not been elucidated.

Limited expression of cancer-testis antigens in renal cell carcinoma patients.

The aim of this study was to evaluate the frequency of expression of the cancer-testis antigens (CTAs) NY-ESO-1, MAGE-A4 and SAGE, in renal cell carcinoma (RCC) patients compared to that in head and neck cancer (HNC) patients, which represent a positive control with a high incidence of CTA expression, to identify novel target antigens for immunotherapy. We prospectively examined frozen tissue samples collected from surgery or biopsy from 35 RCC and 40 HNC patients. Total RNA was extracted, and real-time reverse transcription-polymerase chain reaction (RT)-PCR was performed to determine the expression of MAGE-A4, NY-ESO-1 and SAGE.

Dose-dependent effects of NY-ESO-1 protein vaccine complexed with cholesteryl pullulan (CHP-NY-ESO-1) on immune responses and survival benefits of esophageal cancer patients.

Background: Cholesteryl pullulan (CHP) is a novel antigen delivery system for cancer vaccines. This study evaluated the safety, immune responses and clinical outcomes of patients who received the CHP-NY-ESO-1 complex vaccine, Drug code: IMF-001.

Methods: Patients with advanced/metastatic esophageal cancer were enrolled and subcutaneously vaccinated with either 100 μg or 200 μg of NY-ESO-1 protein complexed with CHP.

[Targeting cancer antigen (MAGE-A4, NY-ESO -1) for immunotherapy].

Cancer/testis (CT) antigen is a group of antigens that are expressed in a wide variety of malignant tumors but not in normal adult tissues except for testis. Since CT antigens are immunogenic and highly restricted to tumors, they are considered as ideal targets for cancer immunotherapy. Many clinical studies targeting CT antigens have been tested.

Molecular characterization of two high-palmitic-acid mutant loci induced by X-ray irradiation in soybean.

Palmitic acid is the most abundant (approx. 11% of total fatty acids) saturated fatty acid in conventional soybean seed oil. Increasing the saturated acid content of soybean oil improves its oxidative stability and plasticity.

T-cell receptor gene therapy targeting melanoma-associated antigen-A4 inhibits human tumor growth in non-obese diabetic/SCID/γcnull mice.

Adoptive cell therapy with lymphocytes that have been genetically engineered to express tumor-reactive T-cell receptors (TCR) is a promising approach for cancer immunotherapy. We have been exploring the development of TCR gene therapy targeting cancer/testis antigens, including melanoma-associated antigen (MAGE) family antigens, that are ideal targets for adoptive T-cell therapy. The efficacy of TCR gene therapy targeting MAGE family antigens, however, has not yet been evaluated in vivo.

In vitro development and postvitrification survival of cloned feline embryos derived from preadipocytes.

The aim of the present study was to optimize the conditions for in vitro development and postvitrification survival of somatic cell cloned feline embryos. To determine the effects of cell cycle synchronization of the nuclear donor cells, we cultured preadipocytes under serum starvation or conventional conditions. After two days in serum starvation culture, the proportion of synchronized donor cells at the G0/G1 phase was 91.