Engineered cellular immunotherapies in cancer and beyond

Nature Medicine, Год журнала: 2022, Номер 28(4), С. 678 - 689

Опубликована: Апрель 1, 2022

Язык: Английский

---

From bench to bedside: the history and progress of CAR T cell therapy

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Май 15, 2023

Chimeric antigen receptor (CAR) T cell therapy represents a major breakthrough in cancer care since the approval of tisagenlecleucel by Food and Drug Administration 2017 for treatment pediatric young adult patients with relapsed or refractory acute lymphocytic leukemia. As April 2023, six CAR therapies have been approved, demonstrating unprecedented efficacy B-cell malignancies multiple myeloma. However, adverse events such as cytokine release syndrome immune effector cell-associated neurotoxicity pose significant challenges to therapy. The severity these correlates pretreatment tumor burden, where higher burden results more severe consequences. This observation is supported application CD19-targeted autoimmune diseases including systemic lupus erythematosus antisynthetase syndrome. These indicate that initiating early at low using debulking strategy prior infusion may reduce events. In addition, expensive has limited effectiveness against solid tumors. this article, we review critical steps led groundbreaking explore ongoing efforts overcome challenges. With promise effective safer development, are optimistic broader range will benefit from revolutionary foreseeable future.

Язык: Английский

---

Lipid Nanoparticle (LNP) Enables mRNA Delivery for Cancer Therapy

Advanced Materials, Год журнала: 2023, Номер 35(51)

Опубликована: Май 17, 2023

Abstract Messenger RNA (mRNA) has received great attention in the prevention and treatment of various diseases due to success coronavirus disease 2019 (COVID‐19) mRNA vaccines (Comirnaty Spikevax). To meet therapeutic purpose, it is required that must enter target cells express sufficient proteins. Therefore, development effective delivery systems necessary crucial. Lipid nanoparticle (LNP) represents a remarkable vehicle indeed accelerated applications humans, as several mRNA‐based therapies have already been approved or are clinical trials. In this review, focus on mRNA‐LNP‐mediated anticancer therapy. It summarizes main strategies mRNA‐LNP formulations, discusses representative approaches cancer, points out current challenges possible future directions research field. hoped these delivered messages can help further improve application technology cancer

Язык: Английский

---

CAR T cell therapy for patients with solid tumours: key lessons to learn and unlearn

Nature Reviews Clinical Oncology, Год журнала: 2023, Номер 21(1), С. 47 - 66

Опубликована: Окт. 30, 2023

Язык: Английский

---

An integrated view of anti-inflammatory and antifibrotic targets for the treatment of NASH

Journal of Hepatology, Год журнала: 2023, Номер 79(2), С. 552 - 566

Опубликована: Апрель 14, 2023

Язык: Английский

---

In vivo hematopoietic stem cell modification by mRNA delivery

Science, Год журнала: 2023, Номер 381(6656), С. 436 - 443

Опубликована: Июль 27, 2023

Hematopoietic stem cells (HSCs) are the source of all blood over an individual's lifetime. Diseased HSCs can be replaced with gene-engineered or healthy through HSC transplantation (HSCT). However, current protocols carry major side effects and have limited access. We developed CD117/LNP-messenger RNA (mRNA), a lipid nanoparticle (LNP) that encapsulates mRNA is targeted to cell factor receptor (CD117) on HSCs. Delivery anti-human CD117/LNP-based editing system yielded near-complete correction hematopoietic sickle cells. Furthermore, in vivo delivery pro-apoptotic PUMA (p53 up-regulated modulator apoptosis) CD117/LNP affected function permitted nongenotoxic conditioning for HSCT. The ability target offers regimen HSCT, this platform could basis genome cure genetic disorders, which would abrogate need

Язык: Английский

---

The future of engineered immune cell therapies

Science, Год журнала: 2022, Номер 378(6622), С. 853 - 858

Опубликована: Ноя. 24, 2022

Immune cells are being engineered to recognize and respond disease states, acting as a "living drug" when transferred into patients. Therapies based on immune now clinical reality, with multiple T cell therapies approved for treatment of hematologic malignancies. Ongoing preclinical studies testing diverse strategies modify the fate function applications in cancer, infectious disease, beyond. Here, we discuss current progress treating human therapeutics, emerging engineering, challenges facing field, particular emphasis where most effort has been applied date.

Язык: Английский

---

Induction of Bleb Structures in Lipid Nanoparticle Formulations of mRNA Leads to Improved Transfection Potency

Advanced Materials, Год журнала: 2023, Номер 35(31)

Опубликована: Май 12, 2023

The transfection potency of lipid nanoparticle (LNP) mRNA systems is critically dependent on the ionizable cationic component. LNP composed optimized lipids often display distinctive mRNA-rich "bleb" structures. Here, it shown that such structures can also be induced for LNPs containing nominally less active by formulating them in presence high concentrations pH 4 buffers as sodium citrate, leading to improved potencies both vitro and vivo. Induction bleb structure type buffer employed, with prepared using 300 mm citrate displaying maximum transfection. attributed, at least part, enhanced integrity encapsulated mRNA. It concluded achieved optimizing formulation parameters improve stability optimization achieve may well lead improvements through formation rather than intracellular delivery.

Язык: Английский

---

Ionizable lipid nanoparticles deliver mRNA to pancreatic β cells via macrophage-mediated gene transfer

Science Advances, Год журнала: 2023, Номер 9(4)

Опубликована: Янв. 27, 2023

Systemic messenger RNA (mRNA) delivery to organs outside the liver, spleen, and lungs remains challenging. To overcome this issue, we hypothesized that altering nanoparticle chemistry administration routes may enable mRNA-induced protein expression of reticuloendothelial system. Here, describe a strategy for delivering mRNA potently specifically pancreas using lipid nanoparticles. Our results show nanoparticles containing cationic helper lipids by intraperitoneal produces robust specific in pancreas. Most resultant occurred within insulin-producing β cells. Last, found pancreatic was dependent on horizontal gene transfer peritoneal macrophage exosome secretion, an underappreciated mechanism influences We anticipate will therapies intractable diseases such as diabetes cancer.

Язык: Английский

---

The Past, Present, and Future of Non-Viral CAR T Cells

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Июнь 9, 2022

Adoptive transfer of chimeric antigen receptor (CAR) T lymphocytes is a powerful technology that has revolutionized the way we conceive immunotherapy. The impressive clinical results complete and prolonged response in refractory relapsed diseases have shifted landscape treatment for hematological malignancies, particularly those lymphoid origin, opens up new possibilities solid neoplasms. However, widening use cell therapy hampered by accessibility to viral vectors are commonly used transfection. In era messenger RNA (mRNA) vaccines CRISPR/Cas (clustered regularly interspaced short palindromic repeat–CRISPR-associated) precise genome editing, novel virus-free methods engineering emerging as more versatile, flexible, sustainable alternative next-generation CAR manufacturing. Here, discuss how non-viral can address some limitations gene allow us deliver genetic information stable, effective straightforward manner. particular, main transposon systems such Sleeping Beauty (SB) piggyBac (PB), utilization mRNA, innovative approaches nanotechnology like Lipid-based Polymer-based DNA nanocarriers nanovectors. We also describe most relevant preclinical data recently led trials, related safety efficacy aspects. will provide practical considerations future trials enable successful safe with generation.

Язык: Английский

---