WT1 and PRAME RNA-loaded dendritic cell vaccine as maintenance therapy in de novo AML after intensive induction chemotherapy

Fløisand, Yngvar; Remberger, Mats; Bigalke, Iris; Josefsen, Dag; Vålerhaugen, Helen; Inderberg, Else Marit; Olaussen, Richard W.; Gjertsen, Bjørn Tore; Goedkoop, René; Geiger, Christiane; Prinz, Petra U.; Schnorfeil, Frauke; Pinkernell, Kai; Schendel, Dolores J.; Kvalheim, Gunnar

doi:10.1038/s41375-023-01980-3

Cited by 12 publications

(6 citation statements)

References 28 publications

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“…CR was achieved in 11 of the 20 patients (55%), and CR2 was achieved in 4 of the 6 relapsing patients (67%) who received allo-HSCT after salvage therapy. The OS rate at 5 years was 75% ( 111 ).Lichtenegger et al. performed a phase I study utilizing TLR7/8-mDCs that were transfected with RNA encoding PRAME and WT1 along with CMVpp65.…”

Section: Adoptive Immunotherapymentioning

confidence: 99%

Targeting PRAME for acute myeloid leukemia therapy

Yang,

Chen,

et al. 2024

Front. Immunol.

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Despite significant progress in targeted therapy for acute myeloid leukemia (AML), clinical outcomes are disappointing for elderly patients, patients with less fit disease characteristics, and patients with adverse disease risk characteristics. Over the past 10 years, adaptive T-cell immunotherapy has been recognized as a strategy for treating various malignant tumors. However, it has faced significant challenges in AML, primarily because myeloid blasts do not contain unique surface antigens. The preferentially expressed antigen in melanoma (PRAME), a cancer-testis antigen, is abnormally expressed in AML and does not exist in normal hematopoietic cells. Accumulating evidence has demonstrated that PRAME is a useful target for treating AML. This paper reviews the structure and function of PRAME, its effects on normal cells and AML blasts, its implications in prognosis and follow-up, and its use in antigen-specific immunotherapy for AML.

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Section: Adoptive Immunotherapymentioning

confidence: 99%

Targeting PRAME for acute myeloid leukemia therapy

Yang,

Chen,

et al. 2024

Front. Immunol.

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“…Among the therapeutic possibilities in these circumstances is IT, where DCs enter the scene. They have been considered a promising therapeutic option since they have the ability to interact and activate CD8+ T lymphocytes, NK, and NKT cells, which are mainly responsible for the elimination of neoplastic cells or as an adjunct to boost antigen-specific T cell ITs in AML [ 5 , 70 , 71 , 72 ].…”

Section: Dendritic Cells and Acute Myeloid Leukemiamentioning

confidence: 99%

“…They proposed FDC101 as maintenance therapy for AML patients in CR1. These DC-vaccines were injected for two years to cover the main risk period for relapse in AML patients who achieve CR1 with intensive chemotherapy but are ineligible for allo-HSCT [ 72 ] ( NCT02405338; Table 2 ).…”

Section: Dendritic Cells and Acute Myeloid Leukemiamentioning

confidence: 99%

Dendritic Cells as a Therapeutic Strategy in Acute Myeloid Leukemia: Vaccines

Palomares,

Pina,

Dakhaoui

et al. 2024

Vaccines

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Dendritic cells (DCs) serve as professional antigen-presenting cells (APC) bridging innate and adaptive immunity, playing an essential role in triggering specific cellular and humoral responses against tumor and infectious antigens. Consequently, various DC-based antitumor therapeutic strategies have been developed, particularly vaccines, and have been intensively investigated specifically in the context of acute myeloid leukemia (AML). This hematological malignancy mainly affects the elderly population (those aged over 65), which usually presents a high rate of therapeutic failure and an unfavorable prognosis. In this review, we examine the current state of development and progress of vaccines in AML. The findings evidence the possible administration of DC-based vaccines as an adjuvant treatment in AML following initial therapy. Furthermore, the therapy demonstrates promising outcomes in preventing or delaying tumor relapse and exhibits synergistic effects when combined with other treatments during relapses or disease progression. On the other hand, the remarkable success observed with RNA vaccines for COVID-19, delivered in lipid nanoparticles, has revealed the efficacy and effectiveness of these types of vectors, prompting further exploration and their potential application in AML, as well as other neoplasms, loading them with tumor RNA.

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“…A total of 55% of patients remained in complete remission, while 4 of 6 relapsing patients achieved complete remission after salvage therapy and underwent allo-HSCT. The vaccine also increased five-year long-term survival to 75% [119]. Strategies that employ histone deacetylase inhibitors and demethylation agents also seem plausible.…”

Section: Prame As a Target For Immunotherapymentioning

confidence: 99%

Preferentially Expressed Antigen in Melanoma Is a Multifaceted Cancer Testis Antigen with Diverse Roles as a Biomarker and Therapeutic Target

Bose

2023

IJTM

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Preferentially expressed antigen in melanoma (PRAME) is a cancer testis antigen (CTA) that is selectively expressed in certain somatic tissues, predominantly in the testis, and is overexpressed in various cancers. PRAME family proteins are leucine-rich repeat proteins that are localized in the nucleus and cytoplasm, with multifaceted roles in immunity, during gametogenesis and in the overall reproduction process. It is a widely studied CTA and has been associated with the prognosis and therapeutic outcomes in patients with epithelial and non-epithelial tumors. PRAME has also been studied extensively as a therapeutic target. Moreover, it has been found to play a role in most of the well-known cancer hallmarks. Interestingly, the role of PRAME in tumorigenesis is paradoxical. Over the last decade, PRAME has garnered substantial interest as a target for immunotherapy. There are multiple clinical trials and pre-clinical studies targeting PRAME alone or in combination with other tumor antigens. This review article is an attempt to update our knowledge and understanding of the context-dependent oncogenic functions of PRAME in various carcinomas, and the current immunotherapeutic strategies, challenges, and perspectives on developing newer strategies to target PRAME for a better outcome.

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WT1 and PRAME RNA-loaded dendritic cell vaccine as maintenance therapy in de novo AML after intensive induction chemotherapy

Cited by 12 publications

References 28 publications

Targeting PRAME for acute myeloid leukemia therapy

Targeting PRAME for acute myeloid leukemia therapy

Dendritic Cells as a Therapeutic Strategy in Acute Myeloid Leukemia: Vaccines

Preferentially Expressed Antigen in Melanoma Is a Multifaceted Cancer Testis Antigen with Diverse Roles as a Biomarker and Therapeutic Target

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