Continuous dependence of the Cauchy problem for the inhomogeneous biharmonic NLS equation in Sobolev spaces

In this paper, we study the continuous dependence of the Cauchy problem for the inhomogeneous biharmonic nonlinear Schr\"{o}dinger (IBNLS) equation $$iu_{t} +\Delta^{2} u=\lambda |x|^{-b}|u|^{\sigma}u,~u(0)=u_{0} \in H^{s} (\mathbb R^{d}),$$ in the standard sense in $H^s$, i.e. in the sense that the local solution flow is continuous $H^s\to H^s$. Here $d\in \mathbb N$, $s>0$, $\lambda\in \mathbb R$ and $\sigma>0$. To arrive at this goal, we first obtain the estimates of the term $f(u)-f(v)$ in the fractional Sobolev spaces which generalize the similar results of An-Kim [5](2021) and Dinh [16](2018), where $f(u)$ is a nonlinear function that behaves like $\lambda |u|^{\sigma}u$ with $\lambda\in \mathbb R$. These estimates are then applied to obtain the standard continuous dependence result for IBNLS equation with $0<s <\min \{2+\frac{d}{2},\frac{3}{2}d\}$, $0<b<\min\{4,d,\frac{3}{2}d-s,\frac{d}{2}+2-s\}$ and $0<\sigma< \sigma_{c}(s)$, where $\sigma_{c}(s)=\frac{8-2b}{d-2s}$ if $s<\frac{d}{2}$, and $\sigma_{c}(s)=\infty$ if $s\ge \frac{d}{2}$. Our continuous dependence result generalizes that of Liu-Zhang [27](2021) by extending the validity of $s$ and $b$.Comment: 25pages. arXiv admin note: text overlap with arXiv:2206.0669

Agonistic Anti-CD137 Monoclonal Antibody Treatment Induces CD11b+Gr-1+ Myeloid-derived Suppressor Cells

CD137 (4-1BB/tnfrsf9) has been shown to co-stimulate T cells. However, agonistic anti-CD137 monoclonal antibody (mAb) treatment can suppress CD4+ T cells, ameliorating autoimmune diseases, whereas it induces activation of CD8+ T cells, resulting in diverse therapeutic activity in cancer, viral infection. To investigate the CD137-mediated T cell suppression mechanism, we examined whether anti-CD137 mAb treatment could affect CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs). Intriguingly, anti-CD137 mAb injection significantly increased CD11b+Gr-1+ cells, peaking at days 5 to 10 and continuing for at least 25 days. Furthermore, this cell population could suppress both CD8+ T cells and CD4+ T cells. Thus, this study demonstrated that, for the first time, anti-CD137 mAb treatment could induce CD11b+Gr-1+ MDSCs under normal conditions, suggesting a possible relationship between myeloid cell induction and CD137-mediated immune suppression

Efficacy and safety of BVAC-C in HPV type 16- or 18–positive cervical carcinoma who failed 1st platinum-based chemotherapy: a phase I/IIa study

BackgroundBVAC-C, a B cell– and monocyte-based immunotherapeutic vaccine transfected with recombinant HPV E6/E7, was well tolerated in HPV–positive recurrent cervical carcinoma patients in a phase I study. This phase IIa study investigates the antitumor activity of BVAC-C in patients with HPV 16– or 18–positive cervical cancer who had experienced recurrence after a platinum-based combination chemotherapy.Patients and methodsPatients were allocated to 3 arms; Arm 1, BVAC-C injection at 0, 4, 8 weeks; Arm 2, BVAC-C injection at 0, 4, 8, 12 weeks; Arm 3, BVAC-C injection at 0, 4, 8, 12 weeks with topotecan at 2, 6, 10, 14 weeks. Primary endpoints were safety and objective response rate (ORR) as assessed by an independent radiologist according to Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included the disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS).ResultsOf the 30 patients available for analysis, the ORR was 19.2% (Arm 1: 20.0% (3/15), Arm 2: 33.3% (2/6), Arm3: 0%) and the DCR was 53.8% (Arm 1: 57.1%, Arm 2: 28.6%, Arm3: 14.3%). The median DOR was 7.5 months (95% CI 7.1–not reported), the median PFS was 5.8 months (95% CI 4.2–10.3), and the median OS was 17.7 months (95% CI 12.0–not reported). All evaluated patients showed not only inflammatory cytokine responses (IFN-γ or TNF-α) but also potent E6/E7-specific T cell responses upon vaccinations. Immune responses of patients after vaccination were correlated with their clinical responses.ConclusionBVAC-C represents a promising treatment option and a manageable safety profile in the second-line setting for this patient population. Further studies are needed to identify potential biomarkers of response.Clinical trial registrationClinicalTrials.gov, identifier NCT02866006

Enhanced Immunogenicity of Engineered HER2 Antigens Potentiates Antitumor Immune Responses

For cancer vaccines, the selection of optimal tumor-associated antigens (TAAs) that can maximize the immunogenicity of the vaccine without causing unwanted adverse effects is challenging. In this study, we developed two engineered Human epidermal growth factor receptor 2 (HER2) antigens, K965 and K1117, and compared their immunogenicity to a previously reported truncated HER2 antigen, K684, within a B cell and monocyte-based vaccine (BVAC). We found that BVAC-K965 and BVAC-K1117 induced comparable antigen-specific antibody responses and antigen-specific T cell responses to BVAC-K684. Interestingly, BVAC-K1117 induced more potent antitumor activity than the other vaccines in murine CT26-HER2 tumor models. In addition, BVAC-K1117 showed enhanced antitumor effects against truncated p95HER2-expressing CT26 tumors compared to BVAC-K965 and BVAC-K684 based on the survival analysis by inducing T cell responses against intracellular domain (ICD) epitopes. The increased ICD epitope-specific T cell responses induced by BVAC-K1117 compared to BVAC-K965 and BVAC-K684 were recapitulated in human leukocyte antigen (HLA)-untyped human PBMCs and HLA-A*0201 PBMCs. Furthermore, we also observed synergistic antitumor effects between BVAC-K1117 and anti-PD-L1 antibody treatment against CT26-HER2 tumors. Collectively, our findings demonstrate that inclusion of a sufficient number of ICD epitopes of HER2 in cellular vaccines can improve the antitumor activity of the vaccine and provide a way to optimize the efficacy of anticancer cellular vaccines targeting HER2.Y

Roles of NKT cells in cancer immunotherapy

Cancer immunotherapy has emerged as an effective therapeutic strategy to treat cancer. Among diverse immune populations, invariant natural killer T (iNKT) cells have shown potent antitumor activity by linking innate and adaptive immune systems. Upon activation by lipid antigens on CD1d molecules, iNKT cells rapidly produce various cytokines and trigger antitumor immunity directly or indirectly by activating other antitumor immune cells. Administration of a representative iNKT cell ligand alpha-galactosylceramide (-GalCer) or -GalCer-pulsed APCs effectively stimulates iNKT cells and thereby induces antitumor effects. In this review, we will introduce the biology and importance of NKT cells in antitumor immunity. Previous studies have demonstrated that iNKT cells not only activate various immune cells but also reinvigorate exhausted immune cells in the tumor microenvironment. Furthermore, we will summarize the major clinical trials utilizing iNKT-based immunotherapies.N

Comparison of the antitumor efficacies of Her-2/ neu DNA vaccines inducing contrasting IgG immunity but comparable CTL activity in mice

The relative importance of CTL and antibodies in rejecting Her-2/ neu-expressing tumors was evaluated in preventive and therapeutic models by DNA vaccination. Four human Her-2/ neu-expressing plasmids (pNeu TM, pNeu ECD, pNeu TM-gDs, and pNeu ECD-gDs) were generated encoding either the transmembrane and extracellular domains or the extracellular domain. Interestingly, these plasmids demonstrated substantial difference in inducing Her-2/ neu-specific serum IgG according to their signal sequence when injected in BALB/c mice. pNeu TM and pNeu ECD induced high serum IgG titers. pNeu TM-gDs and pNeu ECD-gDs induced low or very low serum IgG titers, respectively. As a result, mice vaccinated with not only pNeu ECD but also pNeu ECD-gDs exhibited complete eradication of a small number of tumor cells. Nevertheless, when the number of tumor cells was increased in a therapeutic model, only pNeu ECD exhibited statistically significant antitumor immunity. These studies demonstrate that strong CTL may be sufficient in tumor prevention, but the collaboration of CTL and antibody may be required in tumor therapy

한국형출혈열환자 골수세포의 전자현미경 소견

In eight male patients with Korean hemorrhagic fever, electron microscopic observations were made on the bone marrow cells during the early stage of the illness with the following results. 1) Several vacuoles were found in the cytoplasm of the erythrocytes and normoblasts. 2) Plasmacytoid cells rich in the rough endoplasmic reticulum, but not in its granules nor in mitochondria, were increased in number. 3) Phagocytic activities were demonstrated together with well-developed Golgi apparatus in the histiocytes and granulocytes. 4) Most megakaryocytes revealed abundant cytoplasm, the peripheral zone of which was actively producing platelets