Prophylactic and therapeutic antileukemic effects induced by the AAC-11-derived Peptide RT53

Habault, Justine; Kaci, Anna; Pasquereau-Kotula, Ewa; Fraser, Clive S.; Chomienne, Christine; Dombret, Hervé; Braun, Thorsten; Pla, Marika; Poyet, Jean-Luc

doi:10.1080/2162402x.2020.1728871

Cited by 9 publications

(10 citation statements)

References 26 publications

(31 reference statements)

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“…We sought to antagonize the action of AAC-11 by using a panel of synthetic peptides derived from the LZ domain located in its alpha helix 18 (19), fused to a cell penetrating sequence of antennapedia protein of Drosophila melanogaster [also commonly known as penetratin] (RK16 here) (Fig 2A), which can be used as an intracellular delivery method for its cargo (26). These AAC-11 derived peptides act as competitive inhibitors of protein-protein interactions, can prevent AAC-11 anti-apoptotic activities and have shown anti-tumor activities in vitro and in vivo (23–25). RT53 spanned the entire length of the AAC-11 LZ domain (Figure 2A), other peptide spanned progressively smaller region of the LZ domain.…”

Section: Resultsmentioning

confidence: 99%

“…Although the mechanisms associated with its anti-apoptotic activity have not been clearly elucidated, AAC-11 contains several protein interaction domains, including a leucine zipper (LZ) domain (19), and has been proposed to repress apoptotic effectors such as E2F1 (20), Acinus (21) and caspase-2 (22). Synthetic peptides based on the LZ domain sequence of AAC-11 were previously shown to be cytotoxic to cancer cells both in vitro and in a in vivo mouse model of melanoma (23, 24) or acute leukemia (25).…”

Section: Introductionmentioning

confidence: 99%

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Anti-apoptotic clone 11 derived peptides induce in vitro death of CD4+ T cells susceptible to HIV-1 infection

Mikhailova

Valle-Casuso

David

et al. 2020

Preprint

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ABSTRACTHIV-1 successfully establishes long-term infection in its target cells despite viral cytotoxic effects. We have recently shown that cell metabolism is an important factor driving CD4+ T-cell susceptibility to HIV-1 and the survival of infected cells. We show here that expression of anti-apoptotic clone 11 (AAC-11), an anti-apoptotic factor upregulated in many cancers, increased with progressive CD4+ T cell memory differentiation in association with the expression of cell cycle, activation and metabolism genes and correlated with susceptibility to HIV-1 infection. Synthetic peptides based on the LZ domain sequence of AAC-11, responsible for its interaction with molecular partners, were previously shown to be cytotoxic to cancer cells. Here we observed that these peptides also blocked HIV-1 infection by inducing cell death of HIV-1 susceptible primary CD4+ T-cells across all T-cell subsets. The peptides targeted metabolically active cells and had the greatest effect on effector and transitional CD4+ T cell memory subsets. Our results suggest that AAC-11 survival pathway is potentially involved in the survival of HIV-1 infectable cells and provide a proof of principle that some cellular characteristics can be targeted to eliminate the cells offering the best conditions to sustain HIV-1 replication.IMPORTANCEAlthough antiretroviral treatment efficiently blocks HIV multiplication, it cannot eliminate the cells already carrying integrated proviruses. In the search for a HIV cure the identification of new potential targets to selectively eliminate infected cells is of the outmost importance. We show here that peptides derived from the anti-apoptotic clone 11 (AAC-11), which expression levels correlated with susceptibility to HIV-1 infection of CD4+ T-cells, induced cytotoxicity in CD4+ T-cells showing the highest levels of activation and metabolic activity, conditions known to favor HIV-1 infection. Accordingly, CD4+ T-cells that survived the cytotoxic action of the AAC-11 peptides were resistant to HIV-1 replication. Our results identify a new potential molecular pathway to target HIV-1 infection.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anti-apoptotic clone 11 derived peptides induce in vitro death of CD4+ T cells susceptible to HIV-1 infection

Mikhailova

Valle-Casuso

David

et al. 2020

Preprint

Self Cite

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“…However, the neoantigen physicochemical variability is a primary problem associated with the optimal format for combatting cancer by manufacturing personalized cancer vaccines [ 170 ]. Anticancer peptide-conjugate vaccine modalities constitute a new potential cancer treatment [ 171 ].…”

Section: Discussionmentioning

confidence: 99%

Recent Advances in Small Peptides of Marine Origin in Cancer Therapy

et al. 2021

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Cancer is one of the leading causes of death in the world, and antineoplastic drug research continues to be a major field in medicine development. The marine milieu has thousands of biological species that are a valuable source of novel functional proteins and peptides, which have been used in the treatment of many diseases, including cancer. In contrast with proteins and polypeptides, small peptides (with a molecular weight of less than 1000 Da) have overwhelming advantages, such as preferential and fast absorption, which can decrease the burden on human gastrointestinal function. Besides, these peptides are only connected by a few peptide bonds, and their small molecular weight makes it easy to modify and synthesize them. Specifically, small peptides can deliver nutrients and drugs to cells and tissues in the body. These characteristics make them stand out in relation to targeted drug therapy. Nowadays, the anticancer mechanisms of the small marine peptides are still largely not well understood; however, several marine peptides have been applied in preclinical treatment. This paper highlights the anticancer linear and cyclic small peptides in marine resources and presents a review of peptides and the derivatives and their mechanisms.

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“…B16F10 mouse cells treated with RT53 were able to mediate protective effects in a tumor vaccination model [ 98 , 99 ]. In a recent study [ 100 ], the authors demonstrated that RT53 had a direct anti-leukemic effect, both in vitro in cancer cell lines, and in vivo, in an acute promyelocytic leukemia (APL) mouse model. A vaccine consisting of RT53-exposed leukemic blast cells was highly effective at preventing leukemia development both prophylactically and therapeutically via the induction of CD4 + T cell-dependent long-term response.…”

Section: Delivery Of Proteins/enzymes Via Cpps For Cancer Treatmentmentioning

confidence: 99%

TAT for Enzyme/Protein Delivery to Restore or Destroy Cell Activity in Human Diseases

Lichtenstein

Zabit

Hauser

et al. 2021

Life

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Much effort has been dedicated in the recent decades to find novel protein/enzyme-based therapies for human diseases, the major challenge of such therapies being the intracellular delivery and reaching sub-cellular organelles. One promising approach is the use of cell-penetrating peptides (CPPs) for delivering enzymes/proteins into cells. In this review, we describe the potential therapeutic usages of CPPs (mainly trans-activator of transcription protein, TAT) in enabling the uptake of biologically active proteins/enzymes needed in cases of protein/enzyme deficiency, concentrating on mitochondrial diseases and on the import of enzymes or peptides in order to destroy pathogenic cells, focusing on cancer cells.

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Prophylactic and therapeutic antileukemic effects induced by the AAC-11-derived Peptide RT53

Cited by 9 publications

References 26 publications

Anti-apoptotic clone 11 derived peptides induce in vitro death of CD4+ T cells susceptible to HIV-1 infection

Anti-apoptotic clone 11 derived peptides induce in vitro death of CD4+ T cells susceptible to HIV-1 infection

Recent Advances in Small Peptides of Marine Origin in Cancer Therapy

TAT for Enzyme/Protein Delivery to Restore or Destroy Cell Activity in Human Diseases

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