Sensorineural Hearing Loss After Adoptive Cell Immunotherapy for Melanoma Using MART-1 Specific T Cells: A Case Report and Its Pathophysiology

Duinkerken, Charlotte W.; Rohaan, Maartje W.; Weger, Vincent A. de; Lohuis, Peter J. F. M.; Latenstein, Merel N.; Theunissen, Eleonoor A. R.; Balm, Alfons J. M.; Dreschler, Wouter A.; Haanen, John B.A.G.; Zuur, Charlotte L.

doi:10.1097/mao.0000000000002332

Cited by 11 publications

(7 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This idea is not without precedent as cell type-specific promoters have been utilized in the brain, retina and inner ear to target specific groups of cells (Praetorius et al, 2010;Kim et al, 2013;Ingusci et al, 2019;McDougald et al, 2019). Furthermore, some recent adoptive immunotherapy trials using a cell type-specific promoter for melanoma already suggest the possibility for this in relation to the SV (Johnson et al, 2009;Seaman et al, 2012;Duinkerken et al, 2019).…”

Section: Implications For Targeting Gene Therapy To Sv Cell Typesmentioning

confidence: 99%

Single Cell and Single Nucleus RNA-Seq Reveal Cellular Heterogeneity and Homeostatic Regulatory Networks in Adult Mouse Stria Vascularis

Korrapati

Taukulis

Olszewski

et al. 2019

Front. Mol. Neurosci.

128

View full text Add to dashboard Cite

The stria vascularis (SV) generates the endocochlear potential (EP) in the inner ear and is necessary for proper hair cell mechanotransduction and hearing. While channels belonging to SV cell types are known to play crucial roles in EP generation, relatively little is known about gene regulatory networks that underlie the ability of the SV to generate and maintain the EP. Using single cell and single nucleus RNA-sequencing, we identify and validate known and rare cell populations in the SV. Furthermore, we establish a basis for understanding molecular mechanisms underlying SV function by identifying potential gene regulatory networks as well as druggable gene targets. Finally, we associate known deafness genes with adult SV cell types. This work establishes a basis for dissecting the genetic mechanisms underlying the role of the SV in hearing and will serve as a basis for designing therapeutic approaches to hearing loss related to SV dysfunction.

show abstract

Section: Implications For Targeting Gene Therapy To Sv Cell Typesmentioning

confidence: 99%

Single Cell and Single Nucleus RNA-Seq Reveal Cellular Heterogeneity and Homeostatic Regulatory Networks in Adult Mouse Stria Vascularis

Korrapati

Taukulis

Olszewski

et al. 2019

Front. Mol. Neurosci.

128

View full text Add to dashboard Cite

show abstract

“…Patient 6 developed permanent sensorineural hearing loss in one ear, as previously described. 35 Both patients experienced CRS (grade 2 and 3), requiring tocilizumab (8 mg/kg with a maximum of 800 mg), an anti-IL-6 receptor antibody, and local and systemic steroids.…”

Section: Resultsmentioning

confidence: 98%

MART-1 TCR gene-modified peripheral blood T cells for the treatment of metastatic melanoma: a phase I/IIa clinical trial

Rohaan¹,

Gomez-Eerland²,

Berg³

et al. 2022

Immuno-Oncology and Technology

View full text Add to dashboard Cite

“…Increasing affinity and avidity of the TCRs have a reflection on the safety of the T cell therapy. This has been demonstrated in clinical trials with a high affinity rTCR-T cells against melanoma antigen recognized by T cells 1 (MART-1) causing severe toxicities of the skin, eye, and ears [34]. On the contrary, in an earlier clinical trial including melanoma patients, low toxicity and respectable toleration were observed when using a TCR with lower affinity for MART-1 [35].…”

Section: Increasing Affinity and Functional Avidity Of Rtcrs While Mamentioning

confidence: 99%

Gene Augmentation and Editing to Improve TCR Engineered T Cell Therapy against Solid Tumors

et al. 2020

View full text Add to dashboard Cite

Recent developments in gene engineering technologies have drastically improved the therapeutic treatment options for cancer patients. The use of effective chimeric antigen receptor T (CAR-T) cells and recombinant T cell receptor engineered T (rTCR-T) cells has entered the clinic for treatment of hematological malignancies with promising results. However, further fine-tuning, to improve functionality and safety, is necessary to apply these strategies for the treatment of solid tumors. The immunosuppressive microenvironment, the surrounding stroma, and the tumor heterogeneity often results in poor T cell reactivity, functionality, and a diminished infiltration rates, hampering the efficacy of the treatment. The focus of this review is on recent advances in rTCR-T cell therapy, to improve both functionality and safety, for potential treatment of solid tumors and provides an overview of ongoing clinical trials. Besides selection of the appropriate tumor associated antigen, efficient delivery of an optimized recombinant TCR transgene into the T cells, in combination with gene editing techniques eliminating the endogenous TCR expression and disrupting specific inhibitory pathways could improve adoptively transferred T cells. Armoring the rTCR-T cells with specific cytokines and/or chemokines and their receptors, or targeting the tumor stroma, can increase the infiltration rate of the immune cells within the solid tumors. On the other hand, clinical “off-tumor/on-target” toxicities are still a major potential risk and can lead to severe adverse events. Incorporation of safety switches in rTCR-T cells can guarantee additional safety. Recent clinical trials provide encouraging data and emphasize the relevance of gene therapy and gene editing tools for potential treatment of solid tumors.

show abstract

Sensorineural Hearing Loss After Adoptive Cell Immunotherapy for Melanoma Using MART-1 Specific T Cells: A Case Report and Its Pathophysiology

Cited by 11 publications

References 33 publications

Single Cell and Single Nucleus RNA-Seq Reveal Cellular Heterogeneity and Homeostatic Regulatory Networks in Adult Mouse Stria Vascularis

Single Cell and Single Nucleus RNA-Seq Reveal Cellular Heterogeneity and Homeostatic Regulatory Networks in Adult Mouse Stria Vascularis

MART-1 TCR gene-modified peripheral blood T cells for the treatment of metastatic melanoma: a phase I/IIa clinical trial

Gene Augmentation and Editing to Improve TCR Engineered T Cell Therapy against Solid Tumors

Contact Info

Product

Resources

About