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dc.contributor.authorKueberuwa, Gray
dc.contributor.authorKalaitsidou, Milena
dc.contributor.authorCheadle, Eleanor J
dc.contributor.authorHawkins, Robert Edward
dc.contributor.authorGilham, David Edward
dc.date.accessioned2018-03-14T21:18:55Z
dc.date.available2018-03-14T21:18:55Z
dc.date.issued2018-03-30
dc.identifier.citationCD19 CAR T cells expressing IL-12 eradicate lymphoma in fully lymphoreplete mice through induction of host immunity. 2018, 8:41-51 Mol Ther Oncolyticsen
dc.identifier.issn2372-7705
dc.identifier.pmid29367945
dc.identifier.doi10.1016/j.omto.2017.12.003
dc.identifier.urihttp://hdl.handle.net/10541/620831
dc.description.abstractChimeric antigen receptor (CAR) T cell therapy represents a significant advancement in cancer therapy. Larger studies have shown ∼90% complete remission rates against chemoresistant and/or refractory CD19+leukemia or lymphoma. Effective CAR T cell therapy is highly dependent on lymphodepleting preconditioning, which is achieved through chemotherapy or radiotherapy that carries with it significant toxicities. These can exclude patients of low performance status. In order to overcome the need for preconditioning, we constructed fully mouse first and second generation anti-murine CD19 CARs with or without interleukin-12 (IL-12) secretion. To test these CARs, we established a mouse model to reflect the human situation without preconditioning. Murine second generation CAR T cells expressing IL-12 were capable of eradicating established B cell lymphoma with a long-term survival rate of ∼25%. We believe this to be the first study in a truly lymphoreplete model. We provide evidence that IL-12-expressing CAR T cells not only directly kill target CD19+cells, but also recruit host immune cells to an anti-cancer immune response. This finding is critical because lymphodepletion regimens required for the success of current CAR T cell technology eliminate host immune cells whose anti-cancer activity could otherwise be harnessed by strategies such as IL-12-secreting CAR T cells.
dc.language.isoenen
dc.rightsArchived with thanks to Molecular therapy oncolyticsen
dc.titleCD19 CAR T cells expressing IL-12 eradicate lymphoma in fully lymphoreplete mice through induction of host immunity.en
dc.typeArticleen
dc.contributor.departmentInstitute of Cancer Sciences, Manchester Cancer Research Centre Building, Wilmslow Road, Withington, Manchesteren
dc.identifier.journalMolecular Therapy Oncolyticsen
refterms.dateFOA2018-12-17T15:17:25Z
html.description.abstractChimeric antigen receptor (CAR) T cell therapy represents a significant advancement in cancer therapy. Larger studies have shown ∼90% complete remission rates against chemoresistant and/or refractory CD19+leukemia or lymphoma. Effective CAR T cell therapy is highly dependent on lymphodepleting preconditioning, which is achieved through chemotherapy or radiotherapy that carries with it significant toxicities. These can exclude patients of low performance status. In order to overcome the need for preconditioning, we constructed fully mouse first and second generation anti-murine CD19 CARs with or without interleukin-12 (IL-12) secretion. To test these CARs, we established a mouse model to reflect the human situation without preconditioning. Murine second generation CAR T cells expressing IL-12 were capable of eradicating established B cell lymphoma with a long-term survival rate of ∼25%. We believe this to be the first study in a truly lymphoreplete model. We provide evidence that IL-12-expressing CAR T cells not only directly kill target CD19+cells, but also recruit host immune cells to an anti-cancer immune response. This finding is critical because lymphodepletion regimens required for the success of current CAR T cell technology eliminate host immune cells whose anti-cancer activity could otherwise be harnessed by strategies such as IL-12-secreting CAR T cells.


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