cross-hla targeting of intracellular oncoproteins with peptide-centric cars centric CARs - cronulla-peptide-scandal HLA targeting of intracellular oncoproteins with peptide Cross-HLA Targeting of Intracellular Oncoproteins with Peptide-Centric CARs: A Novel Immunotherapeutic Approach

asymchem-peptides-reviews The dominant search intent revolves around understanding and detailing the scientific concept of "cross-HLA targeting of intracellular oncoproteins with peptide-centric CARs.Targeting peptide–HLA complexes for precision ..." This involves exploring a specific type of immunotherapy that utilizes peptide-centric chimeric antigen receptors (CARs) to target intracellular oncoproteins, overcoming limitations imposed by HLA presentation.

Tier 1 Entities & Phrases:

* Core Topic: Cross-HLA targeting of intracellular oncoproteins with peptide-centric CARs

* Key Technology: Peptide-centric CARs (PC-CARs)

* Target: Intracellular oncoproteins

* Mechanism: Cross-HLA targeting, peptide presentation, HLA allotypes

Tier 2 Entities & Phrases:

* Neuroblastoma

* PHOX2B (a specific oncoprotein)

* Counter-panning strategy

* Unmutated peptides

* Immunotherapy

* T cell therapy

Tier 3 Entities & Phrases:

* Specific publication dates, journal names, author names (unless they are crucial for context, which they are not here as the concept is the focus).作者：Y Sun·2023·被引用次数：17—Our results provide a molecular blueprint for engineeringCARswith optimal recognition of tumor-associated antigens in the context of different HLAs.

* Retraction notices (these indicate the topic is still under scientific scrutiny and may not be the primary focus for a general explanation).

* Redundant or overly specific phrasing that doesn't add conceptual valueCitations to Enhanced detection of neoantigen-reactive T ....

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The field of cancer immunotherapy has seen significant advancements, with chimeric antigen receptor (CAR) T-cell therapy emerging as a powerful tool. However, a major limitation has been the inability to effectively target intracellular oncoproteins, which constitute the majority of cancer-driving proteins. A groundbreaking approach, termed cross-HLA targeting of intracellular oncoproteins with peptide-centric CARs, has been developed to overcome this challenge. This innovative strategy utilizes peptide-centric CARs (PC-CARs) to recognize intracellular oncoproteins presented on the cell surface via Human Leukocyte Antigen (HLA) molecules, thereby expanding the scope of immunotherapeutic targets作者：M Yarmarkovich·2023—This retracts the article "RETRACTED ARTICLE:Cross-HLA targeting of intracellular oncoproteins with peptide-centric CARs" in volume 599 on page ....

The Challenge of Intracellular Oncoproteins

Oncogenic drivers, many of which are intracellular proteins, are responsible for cancer development and progression. Traditional immunotherapies, including CAR T-cell therapy, primarily target surface antigensThe study describesPC-CARs targeting the neuroblastoma oncoprotein PHOX2B presented on HLA. These CARs kill tumor cells across multiple HLA allotypes.. This leaves a vast pool of intracellular oncoproteins inaccessible to current treatment modalities.2026年1月12日—De novo-designed proteinCAR-T cell therapy uses computationally engineered proteins that recognizepeptide–HLA(pHLA) complexes as antigen- ... To address this, researchers have focused on identifying ways to present fragments of these intracellular proteins, known as peptides, on the cell surface. These peptides are then loaded onto HLA molecules, which act as presenters to T-cells. However, the diversity of HLA types across individuals (HLA polymorphism) presents a significant hurdle, as a CAR designed to recognize a specific peptide-HLA complex might only be effective in a subset of patients....Cross-HLA targeting of intracellular oncoproteins with peptide-centric CARs. Nature, 599(7885):477-484(2021) [pubmed]. Keyword List. submitter keyword ...

Peptide-Centric CARs: A Solution for Broad Targeting

The development of peptide-centric CARs represents a significant leap forwardResearchers develop a new class of CAR-T cells that .... Unlike conventional CARs that recognize intact surface proteins, PC-CARs are engineered to specifically bind to peptide-HLA complexes. This "peptide-centric" design allows for the recognition of intracellular oncoproteins that are processed into peptides and presented by HLA molecules.(PDF) Retraction Note: Cross-HLA targeting of intracellular ...

A key innovation in this approach is the development of strategies that enable cross-HLA targeting. This means that a single PC-CAR design can potentially recognize the same target peptide presented by multiple different HLA allotypes. This ability is crucial for developing broadly applicable immunotherapies that can benefit a larger patient population, irrespective of their specific HLA genetic makeup作者：M Yarmarkovich·被引用次数：114—美国费城儿童医院John M. Maris团队通过以肽为中心的CAR实现细胞内肿瘤蛋白的交叉HLA靶向。相关论文于2021年11月3日在线发表在《自然》杂志上。.

Mechanism of Action and Potential Applications

PC-CARs function by binding to the peptide-HLA complex presented on cancer cells. This binding then triggers a T-cell response, leading to the targeted killing of cancer cells.ProteomeXchange Dataset PXD027182 The specificity of the CAR is directed towards peptides derived from oncoproteins, ensuring that the immune system primarily attacks malignant cells while sparing healthy tissues.

Early research has demonstrated the potential of this approach in preclinical models.Citations to Enhanced detection of neoantigen-reactive T ... For instance, PC-CARs targeting the neuroblastoma oncoprotein PHOX2B have shown promising results, completely and selectively eliminating neuroblastoma tumors in mice. This success highlights the therapeutic potential of PC-CARs for various cancers driven by intracellular oncoproteins.2021年11月8日—Cross-HLA targeting of intracellular oncoproteins with peptide-centric CARs. Nature. 2021 599(7885):477-484. Project Files. FTP GLOBUS. Name.

Overcoming HLA Diversity

The inherent diversity of HLA molecules is a major challenge in developing universal cancer therapies. Each individual possesses a unique set of HLA alleles, influencing which peptides are presented on their cell surfaces. Traditional CARs that rely on recognizing specific peptide-HLA complexes would therefore need to be tailored to individual patient HLA types, a complex and costly endeavor.

The cross-HLA targeting capability of peptide-centric CARs aims to circumvent this limitation. By designing CARs that can recognize a specific peptide presented by a wide range of common HLA allotypes, it becomes possible to create off-the-shelf therapies that are effective across diverse patient populations. This is achieved through strategies like counter-panning with predicted potentially cross-reactive peptides, allowing for the engineering of CARs with optimal recognition across different HLAs.2021年11月3日—Kiefel, John M. Maris.Cross-HLA targeting of intracellular oncoproteins with peptide-centric CARs. Nature, 2021; DOI: 10.1038/s41586-021-04061- ...

Future Directions and Implications

The development of peptide-centric CARs for cross-HLA targeting of intracellular oncoproteins opens up new avenues for cancer immunotherapyCitations to Enhanced detection of neoantigen-reactive T .... This approach has the potential to significantly expand the repertoire of treatable cancers by making previously inaccessible intracellular targets available for immune attackCross-HLA targeting of intracellular oncoproteins with peptide .... Further research and clinical trials are necessary to fully realize the promise of this technology, including optimizing CAR design, identifying novel oncoprotein targets, and ensuring safety and efficacy in human patients. The ability to broadly target intracellular oncoproteins represents a significant advancement in the ongoing fight against cancer.CAR-T Cells for Neuroblastoma using MHC Dextramer