<i>Ex vivo</i> enrichment of PRAME antigen‐specific T cells for adoptive immunotherapy using CD137 activation marker selection

Lee, Koon; Gowrishankar, Kavitha; Street, Janine; McGuire, Helen M.; Luciani, Fabio; Hughes, Brendan; Singh, Mandeep; Clancy, Leighton; Gottlieb, David; Micklethwaite, Kenneth; Blyth, Emily

doi:10.1002/cti2.1200

Cited by 9 publications

(11 citation statements)

References 60 publications

(93 reference statements)

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“…11 Interestingly, we could not identify any clinical trial employing PRAME in-situ protein expression as eligibility criteria, which may be due to the lack of properly characterized serological reagents. 12-14 The lack of exact in-situ protein expression data for many antigens is based on methodological differences. While immunological and molecular methods can generate a wealth of novel potentially interesting antigens, protein expression analysis requires serological reagents, which need to be suitable for immunohistochemistry.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Detection of Cancer-Testis Antigen PRAME

et al. 2021

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Cancer-testis (CT) antigens were identified by their ability to elicit T- or B-cell immune responses in the autologous host. They are typically expressed in a wide variety of neoplasms and in normal adult tissues are restricted to testicular germ cells. PReferentially expressed Antigen of Melanoma (PRAME) is a member of the family of nonclassical CT antigens being expressed in a few other normal tissues besides testis. Interestingly, knowledge about the protein expression of many CT antigens is still incomplete due to the limited availability of reagents for their immunohistochemical detection. Here, we tested several commercially available serological reagents and identified a monoclonal antibody suitable for the immunohistochemical detection of PRAME in formalin-fixed paraffin-embedded specimens. We also tested a wide array of normal and neoplastic tissues. PRAME protein expression in normal tissues is congruent with original molecular data being present in the testis, and at low levels in the endometrium, adrenal cortex, and adult as well as fetal ovary. In tumors, there is diffuse PRAME immunoreactivity in most metastatic melanomas, myxoid liposarcomas, and synovial sarcomas. Other neoplasms such as seminomas and carcinomas of various origins including endometrial, serous ovarian, mammary ductal, lung, and renal showed an intermediate proportion of cases and variable extent of tumor cells positive for PRAME protein expression. As seen with other CT antigens, hepatocellular and colorectal carcinoma, Leydig cell tumors, mesothelioma, and leiomyosarcoma are poor expressers of PRAME.

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Section: Discussionmentioning

confidence: 99%

Immunohistochemical Detection of Cancer-Testis Antigen PRAME

et al. 2021

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“…A favorable approach could be adoptive immunotherapy with ex vivo expanded tumor-specific T cells. A preferential target could be PRAME, which is overexpressed in several cancers including AML [ 50 ]. Ex vivo augmented PRAME-specific T cells established antigen specificity.…”

Section: Immunotherapies Targeting Immunogenic Leukemia-associated An...mentioning

confidence: 99%

“…Ex vivo augmented PRAME-specific T cells established antigen specificity. In further analysis, the predominance of Th1 phenotype was shown, which is associated with beneficial in vivo function and prolonged persistence [ 50 ].…”

Section: Immunotherapies Targeting Immunogenic Leukemia-associated An...mentioning

confidence: 99%

Increasing Role of Targeted Immunotherapies in the Treatment of AML

Greiner

Götz

Wais

2022

IJMS

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Acute myeloid leukemia (AML) is the most common acute leukemia in adults. The standard of care in medically and physically fit patients is intensive induction therapy. The majority of these intensively treated patients achieve a complete remission. However, a high number of these patients will experience relapse. In patients older than 60 years, the results are even worse. Therefore, new therapeutic approaches are desperately needed. One promising approach in high-risk leukemia to prevent relapse is the induction of the immune system simultaneously or after reduction of the initial tumor burden. Different immunotherapeutic approaches such as allogenic stem cell transplantation or donor lymphocyte infusions are already standard therapies, but other options for AML treatment are in the pipeline. Moreover, the therapeutic landscape in AML is rapidly changing, and in the last years, a number of immunogenic targets structures eligible for specific therapy, risk assessment or evaluation of disease course were determined. For example, leukemia-associated antigens (LAA) showed to be critical as biomarkers of disease state and survival, as well as markers of minimal residual disease (MRD). Yet many mechanisms and properties are still insufficiently understood, which also represents a great potential for this form of therapy. Therefore, targeted therapy as immunotherapy could turn into an efficient tool to clear residual disease, improve the outcome of AML patients and reduce the relapse risk. In this review, established but also emerging immunotherapeutic approaches for AML patients will be discussed.

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“…CD137 expression on CD8 + T cells is considered as tumor infiltrating lymphocytes acquiring the effector T cells phenotype and promises the better clinical outcome. [38][39][40] Isolation and ex vivo expansion of the CD137 + , CD8 + T cell population is a key to enhance the efficacy of the adoptive T cell transfer. [39] Finally, up-regulated expression of CD137 on CD8 + T cells co-cultured with human cervical carcinoma demonstrated a great potential of the AuNR platform for activation and ex vivo expansion of T cells.…”

Section: Introductionmentioning

confidence: 99%

The Effect of the Nanoparticle Shape on T Cell Activation

Xia

Wong

et al. 2022

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The mechanism of extracellular ligand nano‐geometry in ex vivo T cell activation for immunotherapy remains elusive. Herein, the authors demonstrate large aspect ratio (AR) of gold nanorods (AuNRs) conjugated on cell culture substrate enhancing both murine and human T cell activation through the nanoscale anisotropic presentation of stimulatory ligands (anti‐CD3(αCD3) and anti‐CD28(αCD28) antibodies). AuNRs with large AR bearing αCD3 and αCD28 antibodies significantly promote T cell expansion and key cytokine secretion including interleukin‐2 (IL‐2), interferon‐gamma (IFN‐γ), and tumor necrosis factor‐alpha (TNF‐α). High membrane tension observed in large AR AuNRs regulates actin filament and focal adhesion assembly and develops maturation‐related morphological features in T cells such as membrane ruffle formation, cell spreading, and large T cell receptor (TCR) cluster formation. Anisotropic stimulatory ligand presentation promotes differentiation of naïve CD8+ T cells toward the effector phenotype inducing CD137 expression upon co‐culture with human cervical carcinoma. The findings suggest the importance of manipulating extracellular ligand nano‐geometry in optimizing T cell behaviors to enhance therapeutic outcomes.

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Ex vivo enrichment of PRAME antigen‐specific T cells for adoptive immunotherapy using CD137 activation marker selection

Cited by 9 publications

References 60 publications

Immunohistochemical Detection of Cancer-Testis Antigen PRAME

Immunohistochemical Detection of Cancer-Testis Antigen PRAME

Increasing Role of Targeted Immunotherapies in the Treatment of AML

The Effect of the Nanoparticle Shape on T Cell Activation

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