Conventional approaches to developing therapeutic cancer vaccines that primarily activate tumor‐specific T cells via dendritic cells (DCs) often demonstrate limited efficacy due to the suboptimal ...activation of these T cells. To address this limitation, here a therapeutic cancer nanovaccine is developed that enhances T cell responses by interacting with both DCs and T cells. The nanovaccine is based on a cancer cell membrane nanoparticle (CCM‐MPLA) that utilizes monophosphoryl lipid A (MPLA) as an adjuvant. To allow direct interaction between the nanovaccine and tumor‐specific T cells, anti‐CD28 antibodies (aCD28) are conjugated onto CCM‐MPLA, resulting in CCM–MPLA–aCD28. This nanovaccine activates tumor‐specific CD8+ T cells in both the presence and absence of DCs. Compared with nanovaccines that interact with either DCs (CCM–MPLA) or T cells (CCM–aCD28), CCM–MPLA–aCD28 induces more potent responses of tumor‐specific CD8+ T cells and exhibits a higher antitumor efficacy in tumor‐bearing mice. No differences in T cell activation efficiency and therapeutic efficacy are observed between CCM–MPLA and CCM–aCD28. This approach may lead to the development of effective personalized therapeutic cancer vaccines prepared from autologous cancer cells.
A nanovaccine comprising cancer cell membrane, monophosphoryl lipid A, and anti‐CD28 antibodies (named CCM–MPLA–aCD28) activates tumor‐specific CD8+ T cells by interacting with both dendritic cells (DCs) and naïve T cells. CCM–MPLA–aCD28 exhibits higher efficacy in tumor‐specific T cell activation and tumor inhibition than nanovaccines that interact with either DCs (CCM–MPLA) or naïve T cells (CCM–aCD28).
Chimeric antigen receptor‐T (CAR‐T) cell immunotherapy has shown impressive clinical outcomes for hematologic malignancies. However, its broader applications are challenged due to its complex ex vivo ...cell‐manufacturing procedures and low therapeutic efficacy against solid tumors. The limited therapeutic effects are partially due to limited CAR‐T cell infiltration to solid tumors and inactivation of CAR‐T cells by the immunosuppressive tumor microenvironment. Here, a facile approach is presented to in vivo program macrophages, which can intrinsically penetrate solid tumors, into CAR‐M1 macrophages displaying enhanced cancer‐directed phagocytosis and anti‐tumor activity. In vivo injected nanocomplexes of macrophage‐targeting nanocarriers and CAR‐interferon‐γ‐encoding plasmid DNA induce CAR‐M1 macrophages that are capable of CAR‐mediated cancer phagocytosis, anti‐tumor immunomodulation, and inhibition of solid tumor growth. Together, this study describes an off‐the‐shelf CAR‐macrophage therapy that is effective for solid tumors and avoids the complex and costly processes of ex vivo CAR‐cell manufacturing.
Chimeric antigen receptor (CAR)‐T cell therapy is costly and challenged for solid tumor treatment. An approach is presented toward in vivo programming of macrophages into CAR‐M1 macrophages to overcome the challenges. In vivo injection of nanocomplexes of macrophage‐targeting nanocarrier and CAR‐M1 macrophage‐inducing DNA generate CAR‐M1 macrophages that facilitate CAR‐mediated cancer phagocytosis, anti‐tumor immunomodulation, and inhibition of solid tumor growth.
Alzheimer's disease (AD), the most common cause of dementia, is a complex condition characterized by multiple pathophysiological mechanisms including amyloid‐β (Aβ) plaque accumulation and ...neuroinflammation in the brain. The current immunotherapy approaches, such as anti‐Aβ monoclonal antibody (mAb) therapy, Aβ vaccines, and adoptive regulatory T (Treg) cell transfer, target a single pathophysiological mechanism, which may lead to unsatisfactory therapeutic efficacy. Furthermore, Aβ vaccines often induce T helper 1 (Th1) cell‐mediated inflammatory responses. Here, a nanovaccine composed of lipid nanoparticles loaded with Aβ peptides and rapamycin is developed, which targets multiple pathophysiological mechanisms, exhibits the combined effects of anti‐Aβ antibody therapy and adoptive Aβ‐specific Treg cell transfer, and can overcome the limitations of current immunotherapy approaches for AD. The Nanovaccine effectively delivers rapamycin and Aβ peptides to dendritic cells, produces both anti‐Aβ antibodies and Aβ‐specific Treg cells, removes Aβ plaques in the brain, alleviates neuroinflammation, prevents Th1 cell‐mediated excessive immune responses, and inhibits cognitive impairment in mice. The nanovaccine shows higher efficacy in cognitive recovery than an Aβ vaccine. Unlike anti‐Aβ mAb therapy and adoptive Treg cell transfer, both of which require complicated and costly manufacturing processes, the nanovaccine is easy‐to‐prepare and cost‐effective. The nanovaccines can represent a novel treatment option for AD.
Rapamycin‐incorporated lipid nanoparticle containing amyloid‐β (LNP‐R/Aβ) attenuates neuroinflammation and improves cognitive function in a transgenic rodent model of Alzheimer's disease (AD) by inducing tolerogenic dendritic cells and Aβ‐specific regulatory T cells, and generating anti‐amyloid antibodies. Furthermore, LNP‐R/Aβ reduces T helper 1 cells in AD brains, implying lower risks of meningitis, which is the major reason for the failure of conventional Aβ vaccines.
Background
Aplasia cutis congenita (ACC) is a rare congenital malformation characterized by a localized absence of skin. which most commonly affects the scalp. We performed the present study to ...elucidate the basic clinical data regarding ACC in Korea, including demographics, clinical features, radiological and therapeutic results.
Methods
Fifty‐nine patients (70 lesions) with ACC (35 from our department and 24 from a Koreamed database search) were enrolled. We assessed demographics, family and obstetrical histories, clinical features (multiplicity, subtype, size, shape, hair collar sign, location, and Frieden's classification), and radiologic and therapeutic results.
Results
The mean age of patients was 2.62 years, with a male‐to‐female ratio of 1.03. A minority of patients had a family history (three patients), birth trauma (one patient), maternal drug use (two patients), or human immunodeficiency virus infection (one patient) during pregnancy, and fetus papyraceus of placental infarcts (two patients). Six patients (6/59, 10.17%) had multiple lesions. Scarring was the most common manifestation (39/70, 55.71%). The scalp was the most commonly affected site (50 cases, 71.43%). Thirty‐nine patients (66.10%) met Frieden's type I classification (scalp ACC without multiple anomalies). Radiological investigations were performed in 30 patients (30/59, 50.85%) with abnormal findings in eight patients. Twenty‐five patients (42.37%) were managed conservatively, and 17 patients (28.81%) were treated with local wound care.
Conclusions
This is the first and largest study assessing the basic clinical data of ACC in Korea. The results of the present study could be useful for pediatricians and dermatologists who routinely manage ACC.
Various immune cells participate in repair and regeneration following tissue injury or damage, orchestrating tissue inflammation and regeneration processes. A deeper understanding of the immune ...system's involvement in tissue repair and regeneration is critical for the development of successful reparatory and regenerative strategies. Here we review recent technologies that facilitate cell-based and biomaterial-based modulation of the immune systems for tissue repair and regeneration. First, we summarize the roles of various types of immune cells in tissue repair. Second, we review the principle, examples, and limitations of regulatory T (Treg) cell-based therapy, a representative cell-based immunotherapy. Finally, we discuss biomaterial-based immunotherapy strategies that aim to modulate immune cells using various biomaterials for tissue repair and regeneration.
The clinical course of generalized pustular psoriasis (GPP) is variable and unpredictable. Sufficient data on the clinical course of the disease has not been reported due to its rarity. To ...investigate the clinical features and course of GPP according to its subtypes, medical records of patients diagnosed with GPP from 2002 to 2012 at two tertiary hospitals were reviewed. The data included patient demographics, associated symptoms, aggravating factors, patterns of relapse and prognosis. Thirty‐three patients with GPP were included in our study, with a mean age of 45.6 years and a male : female ratio of 1:1.2. Patients were categorized based on the following subtypes: acute GPP, 21 (63.6%); GPP of pregnancy, two (6.1%); juvenile GPP, three (9.1%); and annular GPP, seven (21.2%). In the acute GPP population, skin lesions cleared within 2 months in 11 (73.3%) patients, and six (40.0%) of these had no relapse. Severe complications, abortion or death, were observed in two patients (100.0%) with GPP of pregnancy. Nineteen (76.0%) of the GPP patients experienced persistence or relapse of skin lesions. The patterns of skin lesions upon relapse included plaques in six patients (31.6%), pustules in eight patients (42.1%), and plaques and pustules in five patients (26.3%). Among acute GPP patients, 16.7% of patients with no relapse had a history of plaque psoriasis. However, 77.8% of patients with persistence and relapse in their clinical course had a history of plaque psoriasis. In conclusion, our study presents the detailed clinical course of GPP by subtype in Korean patients.
The development of therapeutic cancer vaccines (TCVs) that provide clinical benefits is challenging mainly due to difficulties in identifying immunogenic tumor antigens and effectively inducing ...antitumor immunity. Furthermore, there is an urgent need for personalized TCVs because only a limited number of tumor antigens are shared among cancer patients. Several autologous nanovaccines that do not require the identification of immunogenic tumor antigens have been proposed as personalized TCVs. However, these nanovaccines generally require exogenous adjuvants (e.g., Toll-like receptor agonists) to improve vaccine immunogenicity, which raises safety concerns. Here, we present senescent cancer cell-derived nanovesicle (SCCNV) as a personalized TCV that provides patient-specific tumor antigens and improved vaccine immunogenicity without the use of exogenous adjuvants. SCCNVs are prepared by inducing senescence in cancer cells ex vivo and subsequently extruding the senescent cancer cells through nanoporous membranes. In the clinical setting, SCCNVs can be prepared from autologous cancer cells from the blood of liquid tumor patients or from tumors surgically removed from solid cancer patients. SCCNVs also contain interferon-γ and tumor necrosis factor-α, which are expressed during senescence. These endogenous cytokines act as adjuvants and enhance vaccine immunogenicity, avoiding the need for exogenous adjuvants. Intradermally injected SCCNVs effectively activate dendritic cells and tumor-specific T cells and inhibit primary and metastatic tumor growth and tumor recurrence. SCCNV therapy showed an efficacy similar to that of immune checkpoint blockade (ICB) therapy and synergized with ICB. SCCNVs, which can be prepared using a simple and facile procedure, show potential as personalized TCVs.
Onychophagia: detailed clinical characteristics Shin, Jun‐Oh; Roh, Dongyoung; Son, Jin‐Hwa ...
International journal of dermatology,
March 2022, 2022-Mar, 2022-03-00, 20220301, Letnik:
61, Številka:
3
Journal Article
Recenzirano
Background
Onychophagia is a common disorder affecting 20% to 30% of the general population. It is defined as habitual nail biting and can cause various changes in the nail units. However, to date, ...there has been a paucity of data focusing on nail deformities related to onychophagia. This study was performed to investigate the clinical characteristics of onychophagia in Korea.
Methods
This study included 53 patients with onychophagia who visited the Pusan National University Hospital (Busan and Yangsan) over a 10‐year period (2011–2020). We retrospectively reviewed medical records and clinical and dermoscopic photographs.
Results
All 10 fingernails were affected in 37.7% of the patients. The left thumbnail was the most predominantly affected site (81.1%). Clinical findings showed that short nails with ragged distal borders were the most common presentation (100.0%), followed by generalized or patchy rough areas (50.9%), linear and pinpoint hemorrhage (32.1%), longitudinal melanonychia (30.2%), transverse groove (28.3%), brittleness (28.3%), macrolunula (24.5%), washboard nail (13.2%), and pterygium (3.8%). Of the patients, 88.7% had periungual complications, such as periungual exfoliation (77.4%), absent or ragged cuticle (52.8%), hyponychial hyperkeratosis (37.7%), and paronychia (15.1%).
Conclusions
Although onychophagia is a common disorder, its clinical characteristics have not been reported in the literature. The results of this study may be helpful in managing patients with onychophagia.
Ultrasonographic findings of pediatric dermoid cyst Ha, Dae‐Lyong; Kim, Tae‐Rim; Shin, Kihyuk ...
Pediatrics international,
April 2021, 2021-Apr, 2021-04-00, 20210401, Letnik:
63, Številka:
4
Journal Article
Recenzirano
Background
The precise diagnosis of dermoid cysts, which are usually located deeper than other common cysts, is important because dermoid cysts occasionally recur after incomplete excision. ...Ultrasonography (US) could give useful preoperative information of dermoid cysts but only a few studies have been conducted on US findings related to dermoid cysts. This study aimed to investigate clinical and US findings on pediatric dermoid cysts.
Methods
We retrospectively reviewed the medical records, clinical photographs, and US findings of 31 pediatric patients (≤18 years of age) with histopathologically diagnosed dermoid cysts who visited the Pusan National University Hospital between 2007 and 2016.
Results
Of the 31 patients, 25 underwent ultrasonography. The mean long diameter, short diameter, and depth of the cysts were 12.7, 9.0, and 3.8 mm, respectively. Sixteen cysts (64%) were ovoid, 23 (92%) showed hypoechogenicity, 20 (80%) showed heterogeneity, 19 (76%) showed well‐demarcated outer margins, and all cysts showed positive posterior acoustic enhancement. All cysts extended to the subcutaneous tissue, and 15 (60%) showed a connection with the underlying muscle.
Conclusions
Ultrasonography may be a useful diagnostic method to visualize the extent and location of the dermoid cyst and make an accurate diagnosis prior to surgical intervention.
