A Systematic Review of Potential Immunotherapies Targeting PRAME in Retinoid Resistant Oral Potentially Malignant Disorders and Oral Cancer

Backgound and Objective: Early chemoprevention in Oral Potentially Malignant Disorders (OPMDs) and Oral Cancer (OC) has been extensively researched in order to mitigate the malignant transformation and progression of the lesion. Many agents have been attempted, but their cost inefficacy and inadequate outcomes posed a major hindrance in their successful adoption. Retinoid Based Therapy (RBT) though a cheap and effective treatment option, could not achieve much clinical usage because of variable responsiveness in clinical outcomes. Such clinical response variability may be attributed to the repression of retinoid receptors by Preferentially Expressed Antigen of Melanoma (PRAME) protein molecule. Therefore, in order to make RBT successful, targeting PRAME by various immunotherapies is an exciting area of research investigation. This review provides an insight into the various immunotherapeutic strategies targeting PRAME and their usefulness in retinoid-resistant OPMD and OC. Method of data collection: An exhaustive internet-based literature search following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was carried out in PUBMED and Google SCHOLAR database using terms ‘Anti-PRAME’ OR ‘PRAME Immunotherapy’ OR ‘PRAME Vaccines’ AND ‘Cancer’ AND ‘Retinoid resistance’. Only articles in the English language with at least 1 citation, published in a journal with impact factor ≥ 1, having relevance to the context and availability of full text were considered. Results: After an initial search, 342 articles were yielded on the basis of inclusion criteria and, by reading the abstract and availability of full text, a total of 124 articles were selected. Further reading the full texts and considering articles from the references of the selected articles, a total of 65 articles were finally included in the review. Conclusion: Our analysis of the literature suggests that PRAME screening in OC and OPMDs prior to RBT should be done. In PRAME positive cases, approaches like PRAME based immunotherapy in the form of Cancer vaccine therapy [Acellular PRAME vaccine, PRAME pulsed Dendritic Cells (DC)]; Adoptive T Cell therapy/T Cell Receptor-T Cell therapy, Antibody therapy/Chimeric Antigen Receptor-T Cell therapy along with Presented antigen modulation Therapies employing histone deacetylase inhibitors and demethylation agents seem plausible. In the future, a combination therapy employing either PRAME vaccines or antibodies or Adoptive T cell Therapy and ATRA could be used in retinoid resistant OC and OPMDs.

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Adoptive T Cell Therapy in Patients With Recurrent Ovarian Cancer

Case Medical Research ◽

10.31525/ct1-nct04072263 ◽

2019 ◽

Author(s):

Keyword(s):

Ovarian Cancer ◽

T Cell ◽

Cell Therapy ◽

Recurrent Ovarian Cancer ◽

Adoptive T Cell Therapy ◽

T Cell Therapy

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Enhanced Sensitivity of Lymphoid Cells to Ethanol ADH Acetaldehyde Toxicity; Implications for GDEPT and Adoptive T Cell Therapy

Current Pharmacogenomics and Personalized Medicine ◽

10.2174/1875692116666180703151538 ◽

2018 ◽

Vol 16 (2) ◽

pp. 118-123

Author(s):

Philip Savage ◽

Claire Horlock ◽

Bryony Stott ◽

Justin Stebbing

Keyword(s):

T Cell ◽

Cell Therapy ◽

Lymphoid Cells ◽

Adoptive T Cell Therapy ◽

T Cell Therapy ◽

Enhanced Sensitivity

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'Off-the-shelf’ allogeneic antigen-specific adoptive T-cell therapy for the treatment of multiple EBV-associated malignancies

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001608 ◽

2021 ◽

Vol 9 (2) ◽

pp. e001608

Author(s):

Debottam Sinha ◽

Sriganesh Srihari ◽

Kirrliee Beckett ◽

Laetitia Le Texier ◽

Matthew Solomon ◽

...

Keyword(s):

T Cell ◽

Cell Therapy ◽

Adoptive T Cell Therapy ◽

Nuclear Antigen ◽

T Cell Therapy ◽

In Vivo Models ◽

Hla Alleles ◽

Cell Therapies ◽

Wide Range

BackgroundEpstein-Barr virus (EBV), an oncogenic human gammaherpesvirus, is associated with a wide range of human malignancies of epithelial and B-cell origin. Recent studies have demonstrated promising safety and clinical efficacy of allogeneic ‘off-the-shelf’ virus-specific T-cell therapies for post-transplant viral complications.MethodsTaking a clue from these studies, we developed a highly efficient EBV-specific T-cell expansion process using a replication-deficient AdE1-LMPpoly vector that specifically targets EBV-encoded nuclear antigen 1 (EBNA1) and latent membrane proteins 1 and 2 (LMP1 and LMP2), expressed in latency II malignancies.ResultsThese allogeneic EBV-specific T cells efficiently recognized human leukocyte antigen (HLA)-matched EBNA1-expressing and/or LMP1 and LMP2-expressing malignant cells and demonstrated therapeutic potential in a number of in vivo models, including EBV lymphomas that emerged spontaneously in humanized mice following EBV infection. Interestingly, we were able to override resistance to T-cell therapy in vivo using a ‘restriction-switching’ approach, through sequential infusion of two different allogeneic T-cell therapies restricted through different HLA alleles. Furthermore, we have shown that inhibition of the programmed cell death protein-1/programmed death-ligand 1 axis in combination with EBV-specific T-cell therapy significantly improved overall survival of tumor-bearing mice when compared with monotherapy.ConclusionThese findings suggest that restriction switching by sequential infusion of allogeneic T-cell therapies that target EBV through distinct HLA alleles may improve clinical response.

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A modular and controllable T cell therapy platform for acute myeloid leukemia

Leukemia ◽

10.1038/s41375-020-01109-w ◽

2021 ◽

Author(s):

Mohamed-Reda Benmebarek ◽

Bruno L. Cadilha ◽

Monika Herrmann ◽

Stefanie Lesch ◽

Saskia Schmitt ◽

...

Keyword(s):

T Cells ◽

Acute Myeloid Leukemia ◽

T Cell ◽

Cell Therapy ◽

Myeloid Leukemia ◽

Tumor Antigens ◽

Adoptive T Cell Therapy ◽

Single Chain ◽

T Cell Therapy ◽

Acute Myeloid

AbstractTargeted T cell therapy is highly effective in disease settings where tumor antigens are uniformly expressed on malignant cells and where off-tumor on-target-associated toxicity is manageable. Although acute myeloid leukemia (AML) has in principle been shown to be a T cell-sensitive disease by the graft-versus-leukemia activity of allogeneic stem cell transplantation, T cell therapy has so far failed in this setting. This is largely due to the lack of target structures both sufficiently selective and uniformly expressed on AML, causing unacceptable myeloid cell toxicity. To address this, we developed a modular and controllable MHC-unrestricted adoptive T cell therapy platform tailored to AML. This platform combines synthetic agonistic receptor (SAR) -transduced T cells with AML-targeting tandem single chain variable fragment (scFv) constructs. Construct exchange allows SAR T cells to be redirected toward alternative targets, a process enabled by the short half-life and controllability of these antibody fragments. Combining SAR-transduced T cells with the scFv constructs resulted in selective killing of CD33+ and CD123+ AML cell lines, as well as of patient-derived AML blasts. Durable responses and persistence of SAR-transduced T cells could also be demonstrated in AML xenograft models. Together these results warrant further translation of this novel platform for AML treatment.

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