Immunobiology of chimeric antigen receptor T cells and novel designs

Walsh, Zachary; Yang, Yinmeng; Kohler, M. Eric

doi:10.1111/imr.12794

Cited by 17 publications

(10 citation statements)

References 135 publications

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“…[110,[115][116][117]. Abs have also been used to convey particular specificities to effector T cells with good effects in the form of chimeric antigen receptor T cells (CARTs) [118]. Alternative "antibody-like" binders based on protein scaffolds have been developed in the form of designed ankyrin repeat proteins (DARPins), anticalins, affibodies, knottins, and others [119][120][121][122][123].…”

Section: Engineered and Designed Antibodiesmentioning

confidence: 99%

Peptides, Antibodies, Peptide Antibodies and More

Trier

Hansen

Houen

2019

IJMS

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The applications of peptides and antibodies to multiple targets have emerged as powerful tools in research, diagnostics, vaccine development, and therapeutics. Antibodies are unique since they, in theory, can be directed to any desired target, which illustrates their versatile nature and broad spectrum of use as illustrated by numerous applications of peptide antibodies. In recent years, due to the inherent limitations such as size and physical properties of antibodies, it has been attempted to generate new molecular compounds with equally high specificity and affinity, albeit with relatively low success. Based on this, peptides, antibodies, and peptide antibodies have established their importance and remain crucial reagents in molecular biology.

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Section: Engineered and Designed Antibodiesmentioning

confidence: 99%

Peptides, Antibodies, Peptide Antibodies and More

Trier

Hansen

Houen

2019

IJMS

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“…The introduction of chimeric antigen receptor (CAR)-T cells in HSCT opened new insight for the treatment of hematologic malignancies. Despite the very good clinical outcomes given by autologous CAR-T cell therapies against several tumors (240–243), the occurrence of life-threatening side effects such as tumor relapses (240, 244) and higher frequencies of GvHD and cytokine release syndrome onsets (245) have arisen major limitations in the use of allogeneic CAR-T cells. In this regard, engineering CAR-NK and CAR-γδ T cells may provide alternative procedures to improve their anti-tumor potentials, while overcoming allogeneic CAR-T cell therapy obstacles (Table 2) (139, 246–249).…”

Section: Genetic Engineeringmentioning

confidence: 99%

Innate Immune Responses in the Outcome of Haploidentical Hematopoietic Stem Cell Transplantation to Cure Hematologic Malignancies

et al. 2019

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In the context of allogeneic transplant platforms, human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) represents one of the latest and most promising curative strategies for patients affected by high-risk hematologic malignancies. Indeed, this platform ensures a suitable stem cell source immediately available for virtually any patents in need. Moreover, the establishment in recipients of a state of immunologic tolerance toward grafted hematopoietic stem cells (HSCs) remarkably improves the clinical outcome of this transplant procedure in terms of overall and disease free survival. However, the HLA-mismatch between donors and recipients has not been yet fully exploited in order to optimize the Graft vs. Leukemia effect. Furthermore, the efficacy of haplo-HSCT is currently hampered by several life-threatening side effects including the onset of Graft vs. Host Disease (GvHD) and the occurrence of opportunistic viral infections. In this context, the quality and the kinetic of the immune cell reconstitution (IR) certainly play a major role and several experimental efforts have been greatly endorsed to better understand and accelerate the post-transplant recovery of a fully competent immune system in haplo-HSCT. In particular, the IR of innate immune system is receiving a growing interest, as it recovers much earlier than T and B cells and it is able to rapidly exert protective effects against both tumor relapses, GvHD and the onset of life-threatening opportunistic infections. Herein, we review our current knowledge in regard to the kinetic and clinical impact of Natural Killer (NK), γδ and Innate lymphoid cells (ILCs) IRs in both allogeneic and haplo-HSCT. The present paper also provides an overview of those new therapeutic strategies currently being implemented to boost the alloreactivity of the above-mentioned innate immune effectors in order to ameliorate the prognosis of patients affected by hematologic malignancies and undergone transplant procedures.

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“…A CAR is composed of three domains: an ectodomain, the transmembrane region and a cytoplasmic activation tail [6,10]. The ectodomain contains a single-chain variable fragment (scFv), usually derived from antibodies that provides the ability to specifically recognize tumor antigens expressed on cancerous cells [11].…”

Section: Introductionmentioning

confidence: 99%

Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy

et al. 2021

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Due to their efficient recognition and lysis of malignant cells, natural killer (NK) cells are considered as specialized immune cells that can be genetically modified to obtain capable effector cells for adoptive cellular treatment of cancer patients. However, biological and technical hurdles related to gene delivery into NK cells have dramatically restrained progress. Recent technological advancements, including improved cell expansion techniques, chimeric antigen receptors (CAR), CRISPR/Cas9 gene editing and enhanced viral transduction and electroporation, have endowed comprehensive generation and characterization of genetically modified NK cells. These promising developments assist scientists and physicians to design better applications of NK cells in clinical therapy. Notably, redirecting NK cells using CARs holds important promise for cancer immunotherapy. Various preclinical and a limited number of clinical studies using CAR-NK cells show promising results: efficient elimination of target cells without side effects, such as cytokine release syndrome and neurotoxicity which are seen in CAR-T therapies. In this review, we focus on the details of CAR-NK technology, including the design of efficient and safe CAR constructs and associated NK cell engineering techniques: the vehicles to deliver the CAR-containing transgene, detection methods for CARs, as well as NK cell sources and NK cell expansion. We summarize the current CAR-NK cell literature and include valuable lessons learned from the CAR-T cell field. This review also provides an outlook on how these approaches may transform current clinical products and protocols for cancer treatment.

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Immunobiology of chimeric antigen receptor T cells and novel designs

Cited by 17 publications

References 135 publications

Peptides, Antibodies, Peptide Antibodies and More

Peptides, Antibodies, Peptide Antibodies and More

Innate Immune Responses in the Outcome of Haploidentical Hematopoietic Stem Cell Transplantation to Cure Hematologic Malignancies

Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy

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