Neoantigen T-Cell Receptor Gene Therapy in Pancreatic Cancer

Leidner, Rom S.; Silva, Nelson Sanjuan; Huang, Huayu; Sprott, David E.; Zheng, Chunhong; Shih, Yi-Ping; Leung, Amy; Payne, Roxanne; Sutcliffe, Kim; Cramer, Julie; Rosenberg, Steven A.; Fox, Bernard A.; Urba, Walter J.; Tran, Eric

doi:10.1056/nejmoa2119662

Cited by 302 publications

(185 citation statements)

References 25 publications

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“…These have already demonstrated initial, though limited, success in multiple epithelial malignancies [139][140][141][142][143] including cholangiocarcinoma [102], colon [144,145], and breast cancer [146,147]. Similarly, we recently demonstrated the potential of KRAS-specific TCR-T for pancreatic cancer [148]. By extension, HRAS mutations have been identified as a conserved neoantigen potential target for redirected T cell therapy in OSCC [149].…”

Section: Additional Modification Of T Cell Therapy Platformsmentioning

confidence: 96%

Development and therapeutic manipulation of the head and neck cancer tumor environment to improve clinical outcomes

Duhen

Gough

Leidner

et al. 2022

Front. Oral. Health

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The clinical response to cancer therapies involves the complex interplay between the systemic, tumoral, and stromal immune response as well as the direct impact of treatments on cancer cells. Each individual's immunological and cancer histories are different, and their carcinogen exposures may differ. This means that even though two patients with oral tumors may carry an identical mutation in TP53, they are likely to have different pre-existing immune responses to their tumors. These differences may arise due to their distinct accessory mutations, genetic backgrounds, and may relate to clinical factors including previous chemotherapy exposure and concurrent medical comorbidities. In isolation, their cancer cells may respond similarly to cancer therapy, but due to their baseline variability in pre-existing immune responses, patients can have different responses to identical therapies. In this review we discuss how the immune environment of tumors develops, the critical immune cell populations in advanced cancers, and how immune interventions can manipulate the immune environment of patients with pre-malignancies or advanced cancers to improve therapeutic outcomes.

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Section: Additional Modification Of T Cell Therapy Platformsmentioning

confidence: 96%

Development and therapeutic manipulation of the head and neck cancer tumor environment to improve clinical outcomes

Duhen

Gough

Leidner

et al. 2022

Front. Oral. Health

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“…In a recent report, a patient with progressive metastatic pancreatic cancer was treated with a single infusion of autologous T cells that had been genetically engineered to clonally express two allogeneic HLA-C*08:02-restricted TCRs targeting mutant KRAS G12D expressed by the tumors. This patient had regression of visceral metastases, and the response was ongoing at 6 months ( 67 ).…”

Section: Identification Of Immunogenic Neoantigensmentioning

confidence: 97%

Neoantigens and NK Cells: “Trick or Treat” the Cancers?

Khawar

Liang

et al. 2022

Front. Immunol.

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Immunotherapy has become an important treatment strategy for cancer patients nowadays. Targeting cancer neoantigens presented by major histocompatibility complex (MHC) molecules, which emerge as a result of non-synonymous somatic mutations with high immunogenicity, is one of the most promising cancer immunotherapy strategies. Currently, several therapeutic options based on the personalized or shared neoantigens have been developed, including neoantigen vaccine and adoptive T-cell therapy, both of which are now being tested in clinical trials for various malignancies. The goal of this review is to outline the use of neoantigens as cancer therapy targets, with an emphasis on neoantigen identification, clinical usage of personalized neoantigen-based cancer therapy agents, and the development of off-the-shelf products based on shared neoantigens. In addition, we introduce and discuss the potential impact of the neoantigen–MHC complex on natural killer (NK) cell antitumor function, which could be a novel way to boost immune response-induced cytotoxicity against malignancies.

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“…More recently, Leidner et al reported that a patient with progressive metastatic pancreatic cancer was treated with TCR-T cells and had regression of visceral metastases; the response was ongoing at 6 months (NCT03935893). These TCR-T cells were original from the autologous T cells that had been genetically engineered to clonally express two allogeneic HLA-C*08:02–restricted TCRs targeting mutant KRAS (Kirsten rat sarcoma viral oncogene homolog) G12D [ 73 ]. As we know, KRAS mutation is frequent in tumors.…”

Section: Tcr-t Cell Constructionmentioning

confidence: 99%

TCR engineered T cells for solid tumor immunotherapy

et al. 2022

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T cell immunotherapy remains an attractive approach for cancer immunotherapy. T cell immunotherapy mainly employs chimeric antigen receptor (CAR)- and T cell receptor (TCR)-engineered T cells. CAR-T cell therapy has been an essential breakthrough in treating hematological malignancies. TCR-T cells can recognize antigens expressed both on cell surfaces and in intracellular compartments. Although TCR-T cells have not been approved for clinical application, a number of clinical trials have been performed, particularly for solid tumors. In this article, we summarized current TCR-T cell advances and their potential advantages for solid tumor immunotherapy.

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Neoantigen T-Cell Receptor Gene Therapy in Pancreatic Cancer

Cited by 302 publications

References 25 publications

Development and therapeutic manipulation of the head and neck cancer tumor environment to improve clinical outcomes

Development and therapeutic manipulation of the head and neck cancer tumor environment to improve clinical outcomes

Neoantigens and NK Cells: “Trick or Treat” the Cancers?

TCR engineered T cells for solid tumor immunotherapy

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