A Bi-Specific T Cell-Engaging Antibody Shows Potent Activity, Specificity, and Tumor Microenvironment Remodeling in Experimental Syngeneic and Genetically Engineered Models of GBM DOI Open Access

Μαρκέλλα Ζαννίκου,

Joseph Duffy, Daniele Procissi

et al.

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

Published: Dec. 21, 2024

Background: Bispecific T cell-engagers (BTEs) are engineered antibodies that redirect cells to target antigen-expressing tumors. BTEs targeting tumor-specific antigens such as interleukin 13 receptor alpha 2 (IL13Rα2) and EGFRvIII have been developed for glioblastoma (GBM). However, there is limited mechanistic understanding of the action BTE since prior studies were mostly conducted in immunocompromised animal models. To close this gap, function was assessed immunosuppressive glioma microenvironment (TME) orthotopic genetically mouse models (GEMM) with intact immune systems. Methods: A bridges CD3 epsilon on murine IL13Rα2-positive GBM therapeutic mechanism investigated immunocompetent GBM. Multi-color flow cytometry, single-cell RNA sequencing (scRNA-Seq), multiplex immunofluorescence, multiparametric magnetic resonance imaging (MRI) across multiple pre-clinical used evaluate response. Results: BTE-mediated interactions between triggered cell activation antigen-dependent killing cells. treatment significantly extended survival mice bearing IL13Rα2-expressing de novo forming GEMM. Quantified parametric MR validated data showing a reduction volume decreased viability. Flow cytometric scRNA-seq analyses TME revealed robust increases activated memory decreases myeloid brains following treatment. Conclusions: Our demonstrate benefits preclinical due ability engage host system direct killing, induction immunological memory, modulation TME. These findings provide deeper insight into actions

Language: Английский

CAR-T cell therapy for hematological malignancies: History, status and promise DOI Creative Commons
Chao Wang, Jianpeng Wang, Shusheng Che

et al.

Heliyon, Journal Year: 2023, Volume and Issue: 9(11), P. e21776 - e21776

Published: Nov. 1, 2023

For many years, the methods of cancer treatment are usually surgery, chemotherapy and radiation therapy. Although these help to improve condition, most tumors still have a poor prognosis. In recent immunotherapy has great potential in tumor treatment. Chimeric antigen receptor T-cell (CAR-T) uses patient's own T cells express chimeric receptors. (CAR) recognizes tumor-associated antigens kills cells. CAR-T achieved good results hematological tumors. 2017, FDA approved first for B-cell acute lymphoblastic leukemia (ALL). October same year, treat lymphoma. order enhance therapeutic effect, become research focus years. The structure CAR, targets treatment, adverse reactions improvement measures during process summarized. This review is an attempt highlight possibly forgotten findings advances cell

Language: Английский

Citations

25
Advances in Cell and Immune Therapies for Melanoma DOI Creative Commons

Tanase Timis,

Sanda Buruiana, Delia Dima

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 98 - 98

Published: Jan. 3, 2025

The incidence rate of cutaneous melanoma is on the rise worldwide, due to increased exposure UV radiation, aging populations, and teratogen agents. However, diagnosis more precise, number new cases related improved tools. Despite better early therapies, has remained a significant public health challenge because its aggressive behavior high potential for metastasis. In 2020, constituted approximately 1.3% all cancer deaths that occurred within European Union, thereby highlighting necessity effective prevention, timely diagnosis, sustainable treatment measures, especially as growing occur among younger patients. Melanoma regarded one most inflamed cancers immune cell presence strong response immunotherapy, fueling need development immune-driven innovative treatments. Approved including checkpoint inhibitors (e.g., anti-PD-1 anti-CTLA-4), have notably survival rates in melanoma. limitations PD-1/PD-L1 CTLA-4 axes inhibitors, such low rates, resistance, toxicity, driven continued research advancements strategies. Current clinical trials are exploring various combinations with costimulatory receptor agonists, chemotherapy, targeted other immunotherapies, goal improving outcomes reducing side effects Emerging approaches, adoptive therapy tumor-infiltrating lymphocytes (TILs) oncolytic virotherapy, showing promise. While CAR-T been less successful compared blood cancers, ongoing addressing challenges like tumor microenvironment antigen specificity. This review provides an overview requirement advances these medications, mark step forward management, set bring fresh breath hope

Language: Английский

Citations

1
CAR-T lymphocyte-based cell therapies; mechanistic substantiation, applications and biosafety enhancement with suicide genes: new opportunities to melt side effects DOI Creative Commons

Paula Ercilla-Rodríguez,

Marta Sánchez‐Díez, Nicolás Alegría‐Aravena

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: July 18, 2024

Immunotherapy has made significant strides in cancer treatment with strategies like checkpoint blockade antibodies and adoptive T cell transfer. Chimeric antigen receptor cells (CAR-T) have emerged as a promising approach to combine these overcome their limitations. This review explores CAR-T living drug for treatment. are genetically engineered immune designed target eliminate tumor by recognizing specific antigens. The study involves comprehensive literature on technology, covering structure optimization, generations, manufacturing processes, gene therapy strategies. It examines haematologic cancers solid tumors, highlighting challenges proposing suicide gene-based mechanism enhance safety. results show advancements particularly optimization generation. process improved broader clinical application. However, series of inherent side effects still need be addressed. In conclusion, hold great promise treatment, but ongoing research is crucial improve efficacy safety oncology patients. proposed offers potential solution mitigate including cytokine release syndrome (the most common toxic effect therapy) the associated neurotoxicity.

Language: Английский

Citations

5
Advancements and challenges in mRNA and ribonucleoprotein-based therapies: From delivery systems to clinical applications DOI Creative Commons

Zohre Eftekhari,

Horieh Zohrabi,

Akbar Oghalaie

et al.

Molecular Therapy — Nucleic Acids, Journal Year: 2024, Volume and Issue: 35(3), P. 102313 - 102313

Published: Aug. 19, 2024

The use of mRNA and ribonucleoproteins (RNPs) as therapeutic agents is a promising strategy for treating diseases such cancer infectious diseases. This review provides recent advancements challenges in mRNA- RNP-based therapies, focusing on delivery systems lipid nanoparticles (LNPs), which ensure efficient to target cells. Strategies microfluidic devices are employed prepare LNPs loaded with RNPs, demonstrating effective genome editing protein expression vitro vivo. These applications extend treatment disease management, results therapy using encapsulating Cas9 single-guide RNA. In addition, tissue-specific targeting strategies offer potential improved outcomes reduced off-target effects. Despite progress, optimizing efficiency remain. Future research should enhance efficiency, explore targeting, investigate combination advance clinical translation. conclusion, therapies avenue various have the revolutionize medicine, providing new hope patients worldwide.

Language: Английский

Citations

4
Endocytosis: the match point of nanoparticle-based cancer therapy DOI
Yonglu Li, Xin Gao, Yapeng Li

et al.

Journal of Materials Chemistry B, Journal Year: 2024, Volume and Issue: 12(38), P. 9435 - 9458

Published: Jan. 1, 2024

Nanomedicine has inspired a ground-breaking strategy for cancer therapy. By intelligently assembling diverse moieties to form nanoparticles, numerous functionalities such as controlled release, synergistic efficiency, and

Language: Английский

Citations

4
Engineered Nanoparticles for Enhanced Antitumoral Synergy Between Macrophages and T Cells in the Tumor Microenvironment DOI
Sang-Jun Moon, Mungyo Jung,

Seokhyeong Go

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 10, 2024

Abstract T cells and macrophages have the potential to collaborate eliminate tumor efficiently. Macrophages can through phagocytosis subsequently activate by presenting antigens. The activated cells, in turn, kill redirect tumor‐associated toward an antitumoral M1 phenotype. However, checkpoint molecules expressed on impede collaborative action of these immune cells. Meanwhile, monotherapy with a single inhibitor (ICI) for either or yields suboptimal efficacy cancer patients. To address this challenge, here nanoparticle capable efficiently delivering dual ICIs tumors both is developed. These programmed cell death protein 1 (PD‐1)‐transfected macrophage membrane‐derived nanoparticles (PMMNPs) target provide signal‐regulatory alpha PD‐1 block CD47 death‐ligand (PD‐L1), respectively, PMMNPs enhance macrophage‐mediated antigen presentation, promote activation, induce reprogramming In syngeneic tumor‐bearing mice, demonstrate superior therapeutic compared non‐targeted delivery anti‐CD47 anti‐PD‐L1 antibodies. augmenting interplay between may offer promising avenue immunotherapy.

Language: Английский

Citations

4
The current socioeconomic and regulatory landscape of immune effector cell therapies DOI Creative Commons
Chiranjeevi Sainatham, Devvrat Yadav, Aravind Dilli Babu

et al.

Frontiers in Medicine, Journal Year: 2024, Volume and Issue: 11

Published: Dec. 4, 2024

Immune cell effector therapies, including chimeric antigen receptor (CAR)-T cells, T-cell (TCR) T natural killer (NK) and macrophage-based represent a transformative approach to cancer treatment, harnessing the immune system target eradicate malignant cells. CAR-T therapy, most established among these, involves engineering cells express CARs specific antigens, showing remarkable efficacy in hematologic malignancies like leukemias, B-cell lymphomas, multiple myeloma. Similarly, TCR-modified which reprogram recognize intracellular tumor antigens presented by major histocompatibility complex (MHC) molecules, offer promise for range of solid tumors. NK-cell therapies leverage NK cells' innate cytotoxicity, providing an allogeneic that avoids some immune-related complications associated with T-cell-based therapies. Macrophage-based still early stages development, focus on reprogramming macrophages stimulate response against microenvironment. Despite their promise, socioeconomic regulatory challenges hinder accessibility scalability These treatments are costly, currently exceeding $400,000 per patient, creating significant disparities access based status geographic location. The high manufacturing costs stem from personalized, labor-intensive processes harvesting, modifying, expanding patients' Moreover, logistics delivering these limit reach, particularly low-resource settings. Regulatory pathways further complicate landscape. In United States., Food Drug Administrations' (FDA) accelerated approval cell-based facilitate innovation but do not address cost-related barriers. Europe, European Medicines Agency (EMA) offers adaptive pathways, yet decentralized reimbursement systems create uneven across member states. Additionally, differing standards quality control worldwide pose hurdles global harmonization access. To expand reach multipronged is needed-streamlined frameworks, policies reduce treatment costs, international collaborations standardize manufacturing. Addressing obstacles essential make life-saving accessible broader patient population worldwide. We present literature review current landscape barriers approved standard care therapy at various levels.

Language: Английский

Citations

3
Clinical Progresses and Challenges of Bispecific Antibodies for the Treatment of Solid Tumors DOI Creative Commons

Yuheng Gu,

Qi Zhao

Molecular Diagnosis & Therapy, Journal Year: 2024, Volume and Issue: 28(6), P. 669 - 702

Published: Aug. 22, 2024

In recent years, bispecific antibodies (BsAbs) have emerged as a promising therapeutic strategy against tumors. BsAbs can recruit and activate immune cells, block multiple signaling pathways, deliver payloads directly to tumor sites. This review provides comprehensive overview of the advances in development clinical application for treatment solid We discuss different formats, unique mechanisms action, outcomes most advanced therapy. Several studies also analyzed progress antibodies. However, this distinguishes itself by exploring challenges associated with proposing potential solutions. As field progresses, hold promise redefine cancer paradigms offer new hope patients

Language: Английский

Citations

2
Precision Medicine in Brain Tumors: New Approaches DOI
Meisam Akhlaghdoust,

Sanaz Bordbar,

Mohammad Nikoohemmat

et al.

Springer eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Citations

1
SYSTEMATIC REVIEW BISPECIFIC ANTIBODIES IN RELAPSED REFRACTORY MULTIPLE MYELOMA: A SYSTEMATIC REVIEW OF EFFICACY AND SAFETY IN PHASE I/II/III CLINICAL TRIAL DOI Creative Commons
Syed Ahsan Ali Shah,

Vanessa Owiredu,

Abhijeet Kumar

et al.

Published: March 13, 2024

This study comprehensively evaluates the efficacy and safety of bispecific antibodies (BiAbs). While in treatment relapsed refractory, multiple myeloma (RRMM) through an analysis clinical trials Phase I, II, III. Despite significant progress with established therapies, challenges RRMM persist. Also, it necessitates innovative approaches. BiAbs, their unique capacity to engage dual antigens, show promise overcoming complexities MM. Moreover, also overcomes immunosuppressive microenvironment. The current elucidates key mechanisms action, including T-cell activation. It covers induction tumor cell apoptosis, highlighting transformative potential BiAbs. comparing such as chimeric antigen receptor (CAR)-T therapies anti-CD38 monoclonal antibodies. That situates BiAbs within evolving MM landscape. Thud encourages outcomes from ongoing demonstrate deep responses a favorable profile. And its positioning pivotal addition therapeutics. Hence, synthesis I-III trial findings provides valuable insights, guiding future research towards optimizing safety. ultimately enhances patient challenging realm refractory myeloma.

Language: Английский

Citations

0