An injectable hydrogel enhances intratumoral retention and antitumor efficacy of cytokine immunotherapy in murine triple negative breast tumor models

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: unknown, P. 113761 - 113761

Published: April 1, 2025

Language: Английский

---

Trifunctional antibody-cytokine fusion protein formats for tumor-targeted combination of IL-15 with IL-7 or IL-21

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 30, 2025

Cytokines from the common gamma chain receptor family, such as IL-15, IL-21 and IL-7, show promise for cancer immunotherapy have been incorporated individually into immunocytokine approach. However, their efficacy monotherapy is limited. Here, we investigated molecular design of tumor-directed trifunctional antibody-cytokine fusion proteins a combinatorial approach IL-15 with either IL-7 or IL-21. Various differing in antibody format, cytokine composition arrangement were generated cooperative activity assessed solution bound to target cells. Comparative analysis revealed that formats cytokines positioned at N- C-termini more effective than those arranged series. For former design, effects observed scFv-based (IL-15+IL-7) protein, primarily enhancing proliferation naive T cells, while scFv/Fab-based (IL-15+IL-21) enhanced IFN-y release cytotoxic potential Combining two-in-one molecule was principally advantageous when Greater potency inducing JAK-STAT pathway activation highlighted importance colocalization activation. Compared Fab-based format displayed tendency towards higher targeted lower untargeted settings, emphasizing concept. Thus, this study underscores developing immunocytokines identified central position, particularly promising candidate further drug development.

Language: Английский

---

Exploring the Link between Inflammatory Biomarkers and Head and Neck Cancer: Understanding the Impact of Smoking as a Cancer-Predisposing Factor

Biomedicines, Journal Year: 2024, Volume and Issue: 12(4), P. 748 - 748

Published: March 27, 2024

Head and neck cancer (HNC) is associated with significant morbidity globally, smoking recognized as a key risk factor. This study investigates the interplay between inflammatory biomarkers in HNC development. The involved 50 patients, divided into non-smoking groups, control group of 30 healthy individuals. Serum levels 48 cytokines, chemokines, growth factors, other markers were meticulously assessed. Significant differences an extensive panel observed patient groups controls. Elevated macrophage colony-stimulating factor (M-CSF) both implicated increased activity pathways known for immunomodulation, proliferation, angiogenesis during cancerogenesis. In contrast, non-smokers demonstrated higher interleukin 10 (IL-10) 15 (IL-15), suggesting more robust immune response. Platelet-derived BB (PDGF-BB) particularly high smokers HNC. Smoking seems to alter crucial HNC, potentially affecting disease progression responses treatment. data indicate that may experience aggressive phenotype, while maintain profile suggestive active effective response against

Language: Английский

---

Miraculin Can Contribute to a Reduction in Inflammatory Biomarkers and Cachexia in Malnourished Patients with Cancer and Taste Disorders

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(5), P. 622 - 622

Published: April 25, 2025

Background: In 2022, there were an estimated 20 million new cancer cases and 9.7 deaths. The number of is expected to rise over 35 by 2050, marking a 75% increase from 2022 levels. Twenty eighty-six percent patients suffer taste disorders (TD), which are associated with increased risk malnutrition. Cachectic syndrome linked the presence growth tumors leads systemic inflammation. Synsepalum dulcificum plant whose berries contain miraculin, glycoprotein that transforms sour tastes into sweet can ameliorate TD. Objectives: To evaluate effect regular intake dried miracle (DMBs), novel food containing on biomarkers inflammation cachexia in malnourished TD receiving antineoplastic therapy. Methods: we conducted triple-blind, randomized, placebo-controlled pilot clinical trial. Thirty-one various etiologies who received chemotherapy enrolled this study divided three groups. first group tablet 150 mg DMB (standard dose), high-dose 300 DMB, third placebo for months before each main meal. plasma levels several molecules measured using X-MAP Luminex multiplexing platform. Results: We found decreased IFN-γ standard-dose group. addition, our results suggest downtrend IL-1β groups after intervention (p = 0.093). Moreover, showed reduction tumor-derived molecule proteolysis-inducing factor/dermcidin 0.021). It important highlight positive correlation between IL-6 IL-10 standard group, suggests better balance proinflammatory anti-inflammatory cytokines. Regardless consumption, soluble TNF receptor type II tended decrease treatment responded well 0.011). did not find significant correlations cytokines sensory variables or dietary nutritional status. Conclusions: Our consumption dose along could contribute reducing exhibiting sense, support crucial cachexia. view, it should be considered coadjuvant therapeutics. Future studies molecular signaling pathways specific mechanisms action bioactive compounds within supplements, such as will allow them used target pathogenic malnutrition: NCT05486260.

Language: Английский

---

Targeted LNPs deliver mRNA encoding IL-15 superagonists to balance efficacy and toxicity in cancer therapy

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 12, 2024

Abstract Interleukin-15 (IL-15) emerges as a promising immunotherapeutic candidate in oncology because of its pivotal role modulating both innate and adaptive immunity. However, the therapeutic utility remains concern due to unexpected toxicity. We propose here that mRNA lipid nanoparticle (mRNA-LNP) system can balance issue through targeted delivery increase IL-15 concentration tumor area reduce leakage into circulation. Utilizing Structure-driven TARgeting (STAR) platform, we acquired intellectual property LNP vectors for effective selective local (LNP Local ) pulmonary Lung ). Then superagonists mRNAs were obtained structural optimization sequence screening, showing better activity compared with benchmarker N-803. Subsequently, anti-tumor efficacy evaluated by intratumoural (i.t.) injection intravenous (i.v.) via , respectively. As result, such exhibited activity, less systematic exposure, cytokine related risks than finally verified well tolerability non-human primates (NHPs), confirming potential clinical application. This finding may open up new possibilities treatment lung cancers metastasis cancers.

Language: Английский

---