Checkpoint inhibitors and T-cell therapies have highlighted the critical role of T cells in anti-cancer immunity. However, limitations associated with these treatments drive the need for alternative ...approaches. Here, we engineer red blood cells into artificial antigen-presenting cells (aAPCs) presenting a peptide bound to the major histocompatibility complex I, the costimulatory ligand 4-1BBL, and interleukin (IL)-12. This leads to robust, antigen-specific T-cell expansion, memory formation, additional immune activation, tumor control, and antigen spreading in tumor models in vivo. The presence of 4-1BBL and IL-12 induces minimal toxicities due to restriction to the vasculature and spleen. The allogeneic aAPC, RTX-321, comprised of human leukocyte antigen-A*02:01 presenting the human papilloma virus (HPV) peptide HPV16 E7
, 4-1BBL, and IL-12 on the surface, activates HPV-specific T cells and promotes effector function in vitro. Thus, RTX-321 is a potential 'off-the-shelf' in vivo cellular immunotherapy for treating HPV + cancers, including cervical and head/neck cancers.
Recombinant agonists that activate co-stimulatory and cytokine receptors have shown limited clinical anticancer utility, potentially due to narrow therapeutic windows, the need for coordinated ...activation of co-stimulatory and cytokine pathways and the failure of agonistic antibodies to recapitulate signaling by endogenous ligands. RTX-240 is a genetically engineered red blood cell expressing 4-1BBL and IL-15/IL-15Rα fusion (IL-15TP). RTX-240 is designed to potently and simultaneously stimulate the 4-1BB and IL-15 pathways, thereby activating and expanding T cells and NK cells, while potentially offering an improved safety profile through restricted biodistribution. We assessed the ability of RTX-240 to expand and activate T cells and NK cells and evaluated the in vivo efficacy, pharmacodynamics and tolerability using murine models. Treatment of PBMCs with RTX-240 induced T cell and NK cell activation and proliferation. In vivo studies using mRBC-240, a mouse surrogate for RTX-240, revealed biodistribution predominantly to the red pulp of the spleen, leading to CD8 + T cell and NK cell expansion. mRBC-240 was efficacious in a B16-F10 melanoma model and led to increased NK cell infiltration into the lungs. mRBC-240 significantly inhibited CT26 tumor growth, in association with an increase in tumor-infiltrating proliferating and cytotoxic CD8 + T cells. mRBC-240 was tolerated and showed no evidence of hepatic injury at the highest feasible dose, compared with a 4-1BB agonistic antibody. RTX-240 promotes T cell and NK cell activity in preclinical models and shows efficacy and an improved safety profile. Based on these data, RTX-240 is now being evaluated in a clinical trial.
BackgroundAgonist antibodies and recombinant cytokines have had limited success in the clinic due to three factors: severe toxicity leading to a narrow therapeutic index, the diminished activity of ...an agonistic antibody compared with natural ligand, and the lack of multiple signals needed to effectively activate most cell types. To address these limitations, Rubius Therapeutics has developed RTX-240, an allogeneic cellular therapy using red blood cells genetically engineered to express 4-1BBL and IL-15/IL-15Ra fusion (IL-15TP) in their natural conformation on the cell surface. RTX-240 is designed to recapitulate human biology by broadly stimulating adaptive and innate immunity to generate an anti-tumor response and provide improved safety due to the restricted biodistribution of red blood cells to the vasculature. Here we demonstrate that RTX-240 is highly active in preclinical models.MethodsPBMCs or NK cells were treated with RTX-240 in vitro. mRBC-240 was used for in vivo studies.ResultsTreatment of either PBMCs or isolated NK cells with RTX-240 induced a dose-dependent increase in NK cell activation, proliferation and functionality. These effects were further enhanced with increased 4-1BBL and IL-15TP expression on the surface of RTX-240. NK cell counts, NKp44 and Trail expression were increased 150, 4.6 and 6-fold over media control, respectively. Activation of NK cells with RTX-240, followed by incubation with K562 targets enhanced NK cell cytotoxicity (1.3-2.8 over control), that was accompanied by increased NK cell activation (CD69) and degranulation (CD107a) (3.1-fold and 1.9-fold, respectively). RTX-240-activated NK cells showed higher frequency of CD56dim/CD16+ NK cells, which have been reported to induce natural and ADCC-dependent cytotoxicity. Correspondingly, RTX-240 promoted enhanced ADCC-induced killing of Raji cells when combined with anti-CD20 mAb (1.4-fold over control). Intravenous administration of mRBC-240 to a B16F10 intravenous lung metastases model led to NK cell expansion on Day 4 (3.8-fold over control). These NK cells were cytotoxic (Granzyme B+) and highly proliferative (Ki67+) (1.4-fold and 18.8-fold over control, respectively). Treatment with mRBC-240 increased the frequency of terminally differentiated NK cells (NK1.1+/CD11b+/CD27-/KLRG1+) in the tumor (2.1-fold increase over control). Terminally differentiated NK cells are highly cytotoxic and their frequency in the tumor was strongly correlated with efficacy in this model (p=0.0001).ConclusionsTaken together, these data indicate that RTX-240 promotes NK cell activity and functionality in preclinical models. RTX-240 has now entered a first-in-human Phase 1 trial for the treatment of patients with relapsed/refractory or locally advanced solid tumors, with a planned arm evaluating RTX-240 in relapsed/refractory acute myeloid leukemia.
A healthy lifestyle has been the need of the hour during the COVID 19 pandemic. Analyzing the current lifestyle patterns of many individuals can be the basis for finding solutions toward building a ...healthy future for India.
The study intended to evaluate the current lifestyles of adults in an urban setting in the midst of a pandemic and to examine the diseases that people could face with respect to their current lifestyles.
The research team performed a cross-sectional study.
The survey was conducted in an urban setting in the Pimpri Chinchwad area of Pune, India.
Participants were 500 men and women between the ages of 18 and 25.
The research team created a survey with 13 multiple-choice questions.
The pandemic has taken a toll on people's mental and physical health. Social distancing and staying indoors for long periods are factors that have affected people's mental health.
Efforts need to be made by individuals to focus not only on their physical health but also on their mental health.
INTRODUCTION: In osteoporosis, bone weakens and increases, sudden and unexpected fracture risk. In porousbone, bone mass and its strength decreases. Osteoporosis progresses without any pain and ...symptoms however it can be prevented. After age of 35, bone breakdown overcomes build-up, which result in bone loss. After menopause, bone breakdown (resorption) overcomes new bone building. Thus, osteoporosis, a silent disease can be reflected by low bone density, up to occurrence of fracture. In post-menopausal women osteoporosis is rapidly, emerging health problem. In India, osteoporotic fractures are major causes of morbidity and mortality in elderly women. The aim of present study is to correlate between serum minerals and BMD in pre and postmenopausal women. MATERIALS AND METHODS: Present study is design to find out serum calcium, phosphorous and BMD. 35 women of each pre and post-menopausal groups, were selected with no medical, surgical and gynaecological abnormality. Serum calcium phosphorous is measured by semi auto analyser and BMD is measured by Bone densitometer. RESULTS: On comparison 75% of post-menopausal women are osteoporotic and BMD score is significantly low with significantly decreased serum calcium and phosphorous level than pre-menopausal women. CONCLUSION: There is significant positive correlation of calcium and phosphorous in post-menopausal women. Our study suggests pre and post-menopausal women should take calcium and phosphorous rich foods, whole grains, legumes & fruits and dark green leafy vegetables every day to supplement minerals, if not low supplementation of calcium and phosphorous tablets can be given. KEYWORDS: Pre and Post-Menopausal women, Osteoporosis, BMD, Serum Calcium, Serum Phosphorus
As a part of our continuation studies in developing new derivatives as dual antimicrobial/antitumor agents we describe the synthesis of new (
Z
)-2-(5-arylidene-2,4-dioxothiazolidin-3-yl) acetic acid ...derivatives (
3a
–
m
). The chemical structures of the compound were elucidated by FTIR,
1
H NMR,
13
C NMR, and elemental analysis data. The antimicrobial activity of all products was examined. All newly synthesized compounds were tested for their in vitro anticancer activity against four cancer cell lines. Among the synthesized compounds,
3a
exhibited notable activity against HeLa, HT29, A549, and MCF-7 cell lines with IC
50
values of 55, 40, 38, and 50 μM, respectively. In order to predict the drug likeliness of the synthesized compounds on the guidelines of Lipinski rule of five studies was carried out using Pallas software.
Mouth Dissolving Tablet Review Shraddha Kadam; Sneha Pawar; Sejal Shelke ...
International Journal of Advanced Research in Science, Communication and Technology,
5/2024
Journal Article
Odprti dostop
Mouth dissolving tablet are solid dosage form containing drugs disintegrate in oral cavity with in less than one minute. Mouth dissolving tablet are conventional dosage form like tablet .mouth ...dissolving tablet are developed of good hardness, dose uniformity and easy administration .the serve as first choice of dosage form for pediatrics, geriatrics and travelling patient. MDTs aim are sufficient hardness, integrity and faster disintegration without water. Mouth dissolving tablet are the including content significant, advantages, disadvantages, ideal properties formulation of mouth dissolving tablet, evaluation parameter and selection of super disintegrating agents. Tablet are readily dissolve in saliva within 60 sec
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•Kitchen waste okra peels derived synthesis of nitrogen doped carbon dots (N-CDs) as a fluorescent probe.•N-CDs a fluorescent probe shows sensitivity towards Cr6+ and Mn7+ metal ions ...with instant decolourisation of Mn7+.•The developed fluorescent probe shows sensitivity and selectivity towards 4-nitroaniline (4-NA) and picric acid (PA).•The developed method has good effectivity for real water sample with good recovery rate.•The circular economy based reactivated carbon as an adsorbent for removal of model pollutant dyes.
The present study explores the kitchen waste okra peels derived synthesis of nitrogen doped carbon dots (N-CDs) via simple carbonization followed by reflux method. The synthesized N-CDs was characterized using, TEM, XPS, FTIR, XRD, Raman, UV–Visible and Fluorescence Spectroscopy. The N-CDs emits bright blue emission at 420 nm with 12 % of quantum yield as well as it follows excitation dependent emission. Further, the N-CDs were employed as a fluorescence sensor for detection of hazardous metal ions and nitro compounds. Among various metal ions and nitro compounds, the N-CDs shows fluorescence quenching response towards Cr6+, and Mn7+ metal ions as well as 4-nitroaniline (4-NA) and picric acid (PA) with significant hypsochromic and bathochromic shift for Mn7+, 4-NA and PA respectively. The developed fluorescent probe shows relatively low limit of detection (LOD) of 1.46 µg/mL, 1.05 µg/mL, 2.1 µg/mL and 2.2 µg/mL for the above analytes respectively. The N-CDs did not show any significant interference with coexisting ions and successfully applied for real water sample analysis. In addition, circular economy approach was employed for adsorption of dyes by reactivating leftover waste carbon residue which was obtained after reflux. Thus, the kitchen waste valorization and circular economy approach based N-CDs have potential applications in the field of detection of emerging pollutants, and environmental remediation.
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