DC Field | Value | Language |
---|---|---|
dc.contributor.author | Rodgers, David T. | ko |
dc.contributor.author | Mazagova, Magdalena | ko |
dc.contributor.author | Hampton, Eric N. | ko |
dc.contributor.author | Cao, Yu | ko |
dc.contributor.author | Ramadoss, Nitya S. | ko |
dc.contributor.author | Hardy, Ian R. | ko |
dc.contributor.author | Schulman, Andrew | ko |
dc.contributor.author | Du, Juanjuan | ko |
dc.contributor.author | Wang, Feng | ko |
dc.contributor.author | Singer, Oded | ko |
dc.contributor.author | Ma, Jennifer | ko |
dc.contributor.author | Nunez, Vanessa | ko |
dc.contributor.author | Shen, Jiayin | ko |
dc.contributor.author | Woods, Ashley K. | ko |
dc.contributor.author | Wright, Timothy M. | ko |
dc.contributor.author | Schultz, Peter G. | ko |
dc.contributor.author | Kim, Chan Hyuk | ko |
dc.contributor.author | Young, Travis S. | ko |
dc.date.accessioned | 2016-07-04T06:01:10Z | - |
dc.date.available | 2016-07-04T06:01:10Z | - |
dc.date.created | 2016-05-14 | - |
dc.date.created | 2016-05-14 | - |
dc.date.created | 2016-05-14 | - |
dc.date.issued | 2016-01 | - |
dc.identifier.citation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.113, no.4, pp.459 - 468 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | http://hdl.handle.net/10203/209118 | - |
dc.description.abstract | Chimeric antigen receptor T (CAR-T) cell therapy has produced impressive results in clinical trials for B-cell malignancies. However, safety concerns related to the inability to control CAR-T cells once infused into the patient remain a significant challenge. Here we report the engineering of recombinant antibody-based bifunctional switches that consist of a tumor antigen-specific Fab molecule engrafted with a peptide neo-epitope, which is bound exclusively by a peptide-specific switchable CAR-T cell (sCAR-T). The switch redirects the activity of the bio-orthogonal sCAR-T cells through the selective formation of immunological synapses, in which the sCAR-T cell, switch, and target cell interact in a structurally defined and temporally controlled manner. Optimized switches specific for CD19 controlled the activity, tissue-homing, cytokine release, and phenotype of sCAR-T cells in a dose-titratable manner in a Nalm-6 xenograft rodent model of B-cell leukemia. The sCAR-T-cell dosing regimen could be tuned to provide efficacy comparable to the corresponding conventional CART-19, but with lower cytokine levels, thereby offering a method of mitigating cytokine release syndrome in clinical translation. Furthermore, we demonstrate that this methodology is readily adaptable to targeting CD20 on cancer cells using the same sCAR-T cell, suggesting that this approach may be broadly applicable to heterogeneous and resistant tumor populations, as well as other liquid and solid tumor antigens. | - |
dc.language | English | - |
dc.publisher | NATL ACAD SCIENCES | - |
dc.subject | CHIMERIC ANTIGEN RECEPTOR | - |
dc.subject | ACUTE LYMPHOBLASTIC-LEUKEMIA | - |
dc.subject | ADOPTIVE IMMUNOTHERAPY | - |
dc.subject | CANCER-IMMUNOTHERAPY | - |
dc.subject | MONOCLONAL-ANTIBODY | - |
dc.subject | ADVERSE EVENT | - |
dc.subject | SAFETY SWITCH | - |
dc.subject | IN-VITRO | - |
dc.subject | THERAPY | - |
dc.subject | DESIGN | - |
dc.title | Switch-mediated activation and retargeting of CAR-T cells for B-cell malignancies | - |
dc.type | Article | - |
dc.identifier.wosid | 000368617900010 | - |
dc.identifier.scopusid | 2-s2.0-84955503891 | - |
dc.type.rims | ART | - |
dc.citation.volume | 113 | - |
dc.citation.issue | 4 | - |
dc.citation.beginningpage | 459 | - |
dc.citation.endingpage | 468 | - |
dc.citation.publicationname | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | - |
dc.identifier.doi | 10.1073/pnas.1524155113 | - |
dc.contributor.localauthor | Kim, Chan Hyuk | - |
dc.contributor.nonIdAuthor | Rodgers, David T. | - |
dc.contributor.nonIdAuthor | Mazagova, Magdalena | - |
dc.contributor.nonIdAuthor | Hampton, Eric N. | - |
dc.contributor.nonIdAuthor | Cao, Yu | - |
dc.contributor.nonIdAuthor | Ramadoss, Nitya S. | - |
dc.contributor.nonIdAuthor | Hardy, Ian R. | - |
dc.contributor.nonIdAuthor | Schulman, Andrew | - |
dc.contributor.nonIdAuthor | Du, Juanjuan | - |
dc.contributor.nonIdAuthor | Wang, Feng | - |
dc.contributor.nonIdAuthor | Singer, Oded | - |
dc.contributor.nonIdAuthor | Ma, Jennifer | - |
dc.contributor.nonIdAuthor | Nunez, Vanessa | - |
dc.contributor.nonIdAuthor | Shen, Jiayin | - |
dc.contributor.nonIdAuthor | Woods, Ashley K. | - |
dc.contributor.nonIdAuthor | Wright, Timothy M. | - |
dc.contributor.nonIdAuthor | Schultz, Peter G. | - |
dc.contributor.nonIdAuthor | Young, Travis S. | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | chimeric antigen receptor T cell | - |
dc.subject.keywordAuthor | autologous cell therapy | - |
dc.subject.keywordAuthor | antibody engineering | - |
dc.subject.keywordAuthor | cancer | - |
dc.subject.keywordAuthor | leukemia | - |
dc.subject.keywordPlus | CHIMERIC ANTIGEN RECEPTOR | - |
dc.subject.keywordPlus | ACUTE LYMPHOBLASTIC-LEUKEMIA | - |
dc.subject.keywordPlus | ADOPTIVE IMMUNOTHERAPY | - |
dc.subject.keywordPlus | CANCER-IMMUNOTHERAPY | - |
dc.subject.keywordPlus | MONOCLONAL-ANTIBODY | - |
dc.subject.keywordPlus | ADVERSE EVENT | - |
dc.subject.keywordPlus | SAFETY SWITCH | - |
dc.subject.keywordPlus | IN-VITRO | - |
dc.subject.keywordPlus | THERAPY | - |
dc.subject.keywordPlus | DESIGN | - |
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