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Mite-specific AIT should rely upon a mixture of D. pteronyssinus and D. farinae extracts, manufactured from both feces and bodies. Such a combination is appropriate to treat children and adult Dermatophagoides-allergic patients from Asia, Europe, and North America.

The aim of the present phase I/II study was to evaluate the safety, immune responses and clinical activity of a vaccine based on autologous dendritic cells (DC) loaded with an allogeneic tumor cell lysate in advanced melanoma patients. DC derived from monocytes were generated in serum-free medium containing GM-CSF and IL-13 according to Good Manufacturing Practices. Fifteen patients with metastatic melanoma (stage III or IV) received four subcutaneous, intradermal, and intranodal vaccinations of both DC loaded with tumor cell lysate and DC loaded with hepatitis B surface protein (HBs) and/or tetanus toxoid (TT). No grade 3 or 4 adverse events related to the vaccination were observed. Enhanced immunity to the allogeneic tumor cell lysate and to TAA-derived peptides were documented, as well as immune responses to HBs/TT antigens. Four out of nine patients who received the full treatment survived for more than 20 months. Two patients showed signs of clinical response and received 3 additional doses of vaccine: one patient showed regression of in-transit metastases leading to complete remission. Eighteen months later, the patient was still free of disease. The second patient experienced stabilization of lung metastases for approximately 10 months. Overall, our results show that vaccination with DC loaded with an allogeneic melanoma cell lysate was feasible in large-scale and well-tolerated in this group of advanced melanoma patients. Immune responses to tumor-related antigens documented in some treated patients support further investigations to optimize the vaccine formulation.

When properly activated, macrophages can be tumoricidal, thus making them attractive additions to standard cancer therapies. To this end, tolerance and activity of human autologous IFN-;-activated macrophages, produced in large scale for clinical use (MAK cells), have been assessed in pilot trials in cancer patients. In the present study, we tested the hypothesis that activation of IFN regulatory factor (IRF)-3 and IRF-7, with subsequent type

GATA2 (n 5 1), and 22q11.2 (n 5 4) mutations and deletions, suggesting improved clinical utility of our comprehensively designed target capture.CVID is the most common PID, representing a heterogeneous group of hypogammaglobulinemias of largely unknown molecular defects. Our system established a genetic diagnosis of 22q11.2 deletion syndrome (22q11.2DS) in a patient with CVID in accordance with a previous study, reporting that a subgroup of patients with adult 22q11.2DS could have hypogammaglobinemia. 9 Moreover, the incidence of this syndrome is relatively high compared with that of other PIDs. Therefore patients with CVID should always be evaluated for the possibility of 22q11.2DS. In this context our customized design to capture this chromosomal lesion is useful.Recent studies revealed that newborn screening for T-cell receptor excision circles can efficiently detect infants with severe combined immunodeficiency and complete DiGeorge syndrome (mainly because of 22q11.2DS). 10 Our comprehensive genetic diagnostic system covering virtually all of the PID genes and 22q11.2DS, would provide an effective genetic confirmation test for infants with positive results on T-cell receptor excision circle screening tests, who require precise and rapid genetic diagnoses for appropriate clinical management.In summary, we developed an NGS-based comprehensive, rapid, and efficient PID diagnostic system that could become a first-line genetic analysis of PID-suspected patients, including infants with positive newborn screening results.We thank the patients and family who made this study possible by providing clinical samples. We also thank Ms Yoshie Miura, Ms Yuko Imanishi, and Ms Hiroe Namizaki for their valuable assistance. We acknowledge the Division for Medical Research Engineering, Nagoya University Graduate School of Medicine, for technical support for NGS. Finally, we thank Enago (www.enago.jp) for the English-language review.

We identified the cysteine protease Amb a 11 as a new major allergen from ragweed pollen. Given the similar physicochemical properties shared by the 2 major allergens, we hypothesize that part of the allergenic activity previously ascribed to Amb a 1 is rather borne by Amb a 11.

TIGIT is an immune checkpoint inhibitor expressed by effector CD4 + and CD8 + T, NK cells and regulatory T-cells. Inhibition of TIGIT-ligand binding using antagonistic anti-TIGIT monoclonal antibodies (mAbs) has shown in vitro potential to restore T-cell functions and therapeutic efficacy in murine tumor models when combined with an anti-PD(L)-1 antibody. Here, we demonstrate for the first time, broader TIGIT expression than previously reported in healthy donors and cancer patients: being observed on  T-cells, particularly in CMVseropositive donors and on tumor cells from hematological malignancies such as cutaneous T -cell lymphoma. Quantification of TIGIT density revealed tumor-infiltrating Treg as the population expressing the highest receptor density. Consequently, the therapeutic potential of anti-TIGIT mAbs might be broader than the previously described anti-PD(L)-1 like restoration of  T-cell function. In addition to  T-cell re-invigoration, CD155 also mediated inhibition in  T-cells, an immune population not previously described to be sensitive to TIGIT inhibition, and could be fully prevented via use of an antagonistic anti-TIGIT mAb (EOS884448). In PBMC from cancer patients, as well as TILs from mice, the higher TIGIT expression in Treg correlated with strong antibody-dependent killing and preferential depletion of this highly immunosuppressive population. Accordingly, ADCCenabling anti-TIGIT mAb had superior antitumor activity, that was depending on Fc receptor engagement. In addition, we induced direct killing of TIGIT-expressing tumor cells both in human patient material and animal models, demonstrating strong rational for therapeutic intervention in heme malignancies. These findings reveal broad therapeutic opportunities for anti-TIGIT mAbs in cancer therapeutics.