Longitudinal immune monitoring of patients receiving intratumoral injection of a MART-1 T-cell receptor-transduced cell line (C-Cure 709)

Køllgaard, Tania; Duval, Lone; Kaltoft, Keld; Seremet, Tina; Andersen, Mads Hald; Maase, Hans von der; Straten, Per thor; Hadrup, Sine Reker

doi:10.1080/14653240902923146

Cited by 2 publications

(1 citation statement)

References 27 publications

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“…These requirements can be met by transferring highly effective TCR α/β chain gene pairs from donor antigen-specific T cells into recipient CD8 + T cells, thereby reprogramming them to display the antigen specificity of the donor cell [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26]. Indeed, TCR-engineered autologous T cells have recently been successfully used in human clinical trials to treat melanoma [6], [27], [28], [29], [30], [31], [32].…”

Section: Introductionmentioning

confidence: 99%

Transduction of SIV-Specific TCR Genes into Rhesus Macaque CD8+ T Cells Conveys the Ability to Suppress SIV Replication

et al. 2011

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BackgroundThe SIV/rhesus macaque model for HIV/AIDS is a powerful system for examining the contribution of T cells in the control of AIDS viruses. To better our understanding of CD8+ T-cell control of SIV replication in CD4+ T cells, we asked whether TCRs isolated from rhesus macaque CD8+ T-cell clones that exhibited varying abilities to suppress SIV replication could convey their suppressive properties to CD8+ T cells obtained from an uninfected/unvaccinated animal.Principal FindingsWe transferred SIV-specific TCR genes isolated from rhesus macaque CD8+ T-cell clones with varying abilities to suppress SIV replication in vitro into CD8+ T cells obtained from an uninfected animal by retroviral transduction. After sorting and expansion, transduced CD8+ T-cell lines were obtained that specifically bound their cognate SIV tetramer. These cell lines displayed appropriate effector function and specificity, expressing intracellular IFNγ upon peptide stimulation. Importantly, the SIV suppression properties of the transduced cell lines mirrored those of the original TCR donor clones: cell lines expressing TCRs transferred from highly suppressive clones effectively reduced wild-type SIV replication, while expression of a non-suppressing TCR failed to reduce the spread of virus. However, all TCRs were able to suppress the replication of an SIV mutant that did not downregulate MHC-I, recapitulating the properties of their donor clones.ConclusionsOur results show that antigen-specific SIV suppression can be transferred between allogenic T cells simply by TCR gene transfer. This advance provides a platform for examining the contributions of TCRs versus the intrinsic effector characteristics of T-cell clones in virus suppression. Additionally, this approach can be applied to develop non-human primate models to evaluate adoptive T-cell transfer therapy for AIDS and other diseases.

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Section: Introductionmentioning

confidence: 99%

Transduction of SIV-Specific TCR Genes into Rhesus Macaque CD8+ T Cells Conveys the Ability to Suppress SIV Replication

et al. 2011

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Re-Inventing Intratumoral Immunotherapy for Melanoma

2011

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Immunotherapeutics have been applied intratumorally to manage accessible lesions and to induce systemic immunity in malignant melanoma. Intratumoral bacillus Calmette-Guérin (BCG) has been used for 40 years, and intratumoral BCG, IL-2, IFN-α and imiquimod are recommended as treatment options for patients with in-transit melanoma metastases. Regression of cutaneous metastases can be achieved. Subcutaneous metastases are more refractory, and regression of uninjected, visceral metastases is infrequent. Other microbial products, cytokines, chemicals, immune cells, antibody and viral and plasmid vectors expressing immunologically active molecules have been tested. Antitumor activity has not been demonstrated to be superior to that of intratumoral BCG. There are few controlled trials, and whether survival is impacted with any approach has not yet been established. The immunotherapeutics applied and the intratumoral administration procedure itself can activate responses that are immune inhibitory. More rigorous clinical testing and improved understanding and modulation of regulatory immune responses are necessary.

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Longitudinal immune monitoring of patients receiving intratumoral injection of a MART-1 T-cell receptor-transduced cell line (C-Cure 709)

Cited by 2 publications

References 27 publications

Transduction of SIV-Specific TCR Genes into Rhesus Macaque CD8+ T Cells Conveys the Ability to Suppress SIV Replication

Transduction of SIV-Specific TCR Genes into Rhesus Macaque CD8+ T Cells Conveys the Ability to Suppress SIV Replication

Re-Inventing Intratumoral Immunotherapy for Melanoma

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