The clinical landscape of CAR NK cells DOI Creative Commons

Lasse Vedel Jørgensen,

Emil Birch Christensen, Mike Bogetofte Barnkob

et al.

Experimental Hematology and Oncology, Journal Year: 2025, Volume and Issue: 14(1)

Published: March 27, 2025

Abstract Chimeric antigen receptor (CAR) NK cell therapy has emerged as a promising alternative to CAR T therapy, offering significant advantages in terms of safety and versatility. Here we explore the current clinical landscape cells, their application hematologic malignancies solid cancers, well potential for treating autoimmune disorders. Our analysis draws from data collected 120 trials focused on presents insights into demographics characteristics these studies. We further outline specific targets diseases under investigation, along with major sources, genetic modifications, combination strategies, preconditioning- dosing regimens, manufacturing strategies being utilized. Initial results 16 demonstrate efficacy particularly B malignancies, where response rates are comparable those seen cells but lower severe adverse effects, such cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity (ICANS), graft-versus-host disease (GvHD). However, challenges remain tumor applications, only modest been observed date. reveals that research is increasingly enhancing persistence, broadening therapeutic targets, refining processes improve accessibility scalability. With recent advancements engineering increased predicted become an integral component next-generation immunotherapies, not cancer potentially immune-mediated well.

Language: Английский

Allogeneic natural killer cell therapy DOI Creative Commons
Melissa M. Berrien-Elliott, Miriam T. Jacobs, Todd A. Fehniger

et al.

Blood, Journal Year: 2022, Volume and Issue: 141(8), P. 856 - 868

Published: Nov. 23, 2022

Abstract Interest in adoptive cell therapy for treating cancer is exploding owing to early clinical successes of autologous chimeric antigen receptor (CAR) T lymphocyte therapy. However, limitations using cells and products are apparent as they (1) take weeks generate, (2) utilize a 1:1 donor-to-patient model, (3) expensive, (4) prone heterogeneity manufacturing failures. CAR also associated with significant toxicities, including cytokine release syndrome, immune effector cell–associated neurotoxicity prolonged cytopenias. To overcome these issues, natural killer (NK) being explored an alternative source allogeneic therapies. NK have inherent ability recognize cancers, mediate functions killing communication, do not induce graft-versus-host disease, or syndrome. can be obtained from blood cord derived hematopoietic stem progenitor induced pluripotent cells, expanded cryopreserved off-the-shelf availability. The first wave point-of-care therapies led the current investigated trials promising preliminary results. Basic advances biology cellular engineering new translational strategies block inhibition, enhance broaden target recognition, optimize functional persistence, provide stealth patients’ immunity. This review details biology, well product manufacturing, engineering, combination clinic leading next generation potent, cancers.

Language: Английский

Citations

114
T-BET and EOMES sustain mature human NK cell identity and antitumor function DOI Creative Commons
Pamela Wong, Jennifer A. Foltz, Lily Chang

et al.

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(13)

Published: June 6, 2023

Since T-box transcription factors (TFs) T-BET and EOMES are necessary for initiation of NK cell development, their ongoing requirement mature homeostasis, function, molecular programming remains unclear. To address this, were deleted in unexpanded primary human cells using CRISPR/Cas9. Deleting these TFs compromised vivo anti-tumor response cells. Mechanistically, required normal proliferation persistence vivo. lacking also exhibited defective responses to cytokine stimulation. Single-cell RNA-sequencing revealed a specific transcriptional program cells, which was rapidly lost following deletion. Further, CD56bright acquired an ILCP-like profile with increased expression ILC-3-associated RORC AHR, revealing role TF maintaining phenotypes unexpected suppressing alternative ILC lineages. Our study reveals the critical importance sustained orchestrate function identity.

Language: Английский

Citations

27
Engineering of potent CAR NK cells using non-viral Sleeping Beauty transposition from minimalistic DNA vectors DOI
Tobias Bexte,

Lacramioara Botezatu,

Csaba Miskey

et al.

Molecular Therapy, Journal Year: 2024, Volume and Issue: 32(7), P. 2357 - 2372

Published: May 14, 2024

Language: Английский

Citations

12
Exosome-based nanoparticles and cancer immunotherapy DOI Open Access
Jiarong Ye, Danni Li,

Yiting Jie

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 179, P. 117296 - 117296

Published: Aug. 20, 2024

Over the past decades, cancer immunotherapy has encountered challenges such as immunogenicity, inefficiency, and cytotoxicity. Consequently, exosome-based gained rapid traction a promising alternative. Exosomes, type of extracellular vesicles (EVs) ranging from 50 to 150 nm, are self-originating exhibit fewer side effects compared traditional therapies. Exosome-based encompasses three significant areas: vaccination, co-inhibitory checkpoints, adoptive T-cell therapy. Each these fields leverages inherent advantages exosomes, demonstrating substantial potential for individualized tumor therapy precision medicine. This review aims elucidate reasons behind promise nanoparticles therapies by examining their characteristics summarizing latest research advancements in immunotherapy.

Language: Английский

Citations

10
Genetic ablation of adhesion ligands mitigates rejection of allogeneic cellular immunotherapies DOI Creative Commons
Quirin Hammer, Karlo Perica, Rina M. Mbofung

et al.

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(9), P. 1376 - 1386.e8

Published: July 8, 2024

Allogeneic cellular immunotherapies hold promise for broad clinical implementation but face limitations due to potential rejection of donor cells by the host immune system. Silencing beta-2 microglobulin (B2M) expression is commonly employed evade T cell-mediated host, although absence B2M expected trigger missing-self responses natural killer (NK) cells. Here, we demonstrate that genetic deletion adhesion ligands CD54 and CD58 in B2M-deficient chimeric antigen receptor (CAR) multi-edited induced pluripotent stem cell (iPSC)-derived CAR NK reduces their susceptibility vitro vivo. The limits a unidirectional manner B2M-sufficient settings without affecting antitumor functionality engineered Thus, these data suggest ablation effectively alleviates cells, facilitating universal immunotherapy.

Language: Английский

Citations

9
Advancements and Challenges in Stem Cell Transplantation for Regenerative Medicine DOI Creative Commons

Lingxi Wei,

Wenqi Yan,

Wahid Shah

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(16), P. e35836 - e35836

Published: Aug. 1, 2024

Stem cell transplantation has emerged as a promising avenue in regenerative medicine, potentially facilitating tissue repair degenerative diseases and injuries. This review comprehensively examines recent developments challenges stem transplantation. It explores the identification isolation of various types, including embryonic, induced pluripotent, adult cells derived from multiple sources. Additionally, highlights tissue-specific applications these cells, focusing on bone cartilage regeneration, treatment neurological disorders, management hematological conditions. Future advancements effective resolution current will be crucial fully realizing potential medicine. With responsible ethical practices, field can transform disease injury treatment, ultimately improving quality life for countless individuals.

Language: Английский

Citations

9
Engineering innate immune cells for cancer immunotherapy DOI
Mubin Tarannum,

Xizhong Ding,

Marta Barisa

et al.

Nature Biotechnology, Journal Year: 2025, Volume and Issue: 43(4), P. 516 - 533

Published: April 1, 2025

Language: Английский

Citations

1
Next‐generation chimeric antigen receptors for T‐ and natural killer‐cell therapies against cancer DOI Creative Commons
Ye Li, Katayoun Rezvani, Hind Rafei

et al.

Immunological Reviews, Journal Year: 2023, Volume and Issue: 320(1), P. 217 - 235

Published: Aug. 7, 2023

Adoptive cellular therapy using chimeric antigen receptor (CAR) T cells has led to a paradigm shift in the treatment of various hematologic malignancies. However, broad application this approach for myeloid malignancies and solid cancers been limited by paucity heterogeneity target expression, lack bona fide tumor-specific antigens that can be targeted without cross-reactivity against normal tissues. This may lead unwanted on-target off-tumor toxicities could undermine desired antitumor effect. Recent advances synthetic biology genetic engineering have enabled reprogramming immune effector enhance their selectivity toward tumors, thus mitigating adverse effects. In review, we outline current strategies being explored improve CAR tumor with focus on natural killer (NK) cells, progress made translating these clinic.

Language: Английский

Citations

21
Allogeneic chimeric antigen receptor cell therapies for cancer: progress made and remaining roadblocks DOI
Caroline Diorio, David T. Teachey, Stephan A. Grupp

et al.

Nature Reviews Clinical Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 15, 2024

Language: Английский

Citations

8
Chimeric antigen receptor-natural killer cell therapy: current advancements and strategies to overcome challenges DOI Creative Commons
Jun Kong, Mohammad Auwal Sa’ad,

Hema Manusri Vijayan

et al.

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

Published: April 25, 2024

Chimeric antigen receptor-natural killer (CAR-NK) cell therapy is a novel immunotherapy targeting cancer cells via the generation of chimeric receptors on NK which recognize specific antigens. CAR-NK gaining attention nowadays owing to ability release potent cytotoxicity against without side effects such as cytokine syndrome (CRS), neurotoxicity and graft-versus-host disease (GvHD). do not require priming, thus enabling them be used “off-the-shelf” therapy. Nonetheless, still possesses several challenges in eliminating reside hypoxic immunosuppressive tumor microenvironment. Therefore, this review envisioned explore current advancements limitations well discuss strategies overcome faced by This also aims dissect status clinical trials future recommendations for improving effectiveness safety

Language: Английский

Citations

7