Co-transfer of tumor-specific effector and memory CD8+ T cells enhances the efficacy of adoptive melanoma immunotherapy in a mouse model
dc.contributor.author | Contreras, Amanda | |
dc.contributor.author | Beems, Megan V | |
dc.contributor.author | Tatar, Andrew J | |
dc.contributor.author | Sen, Siddhartha | |
dc.contributor.author | Srinand, Prakrithi | |
dc.contributor.author | Suresh, M. | |
dc.contributor.author | Luther, Tahra K | |
dc.contributor.author | Cho, Clifford S | |
dc.date.accessioned | 2018-06-03T04:00:23Z | |
dc.date.available | 2018-06-03T04:00:23Z | |
dc.date.issued | 2018-05-29 | |
dc.identifier.citation | Journal for ImmunoTherapy of Cancer. 2018 May 29;6(1):41 | |
dc.identifier.uri | https://doi.org/10.1186/s40425-018-0358-2 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/143864 | |
dc.description.abstract | Abstract Background Adoptive cell transfer (ACT) is a promising cancer immunotherapeutic strategy that remains ineffective for a large subset of patients. ACT with memory CD8+ T cells (Tmem) has been shown to have superior efficacy compared to traditional ACT with effector CD8+ T cells (Teff). Teff and Tmem have complementary physiological advantages for immunotherapy, but previous publications have not examined ACT using a combination of Teff and Tmem. Methods Splenocytes harvested from Ly5.1+/C57BL/6 mice during and after infection with lymphocytic choriomeningitis virus (LCMV) were used to generate bona fide effector and memory CD8+ T cells specific for the LCMV epitope peptide GP33. Congenic Ly5.2+/C57BL/6 mice were inoculated with B16F10 melanoma cells transfected to express very low levels of GP33, then treated with ACT 7 days later with GP33-specific Teff, Tmem, or a combination of Teff + Tmem. Results Inhibition of melanoma growth was strongest in mice receiving combinatorial ACT. Although combinatorial ACT and memory ACT resulted in maximal intratumoral infiltration of CD8+ T cells, combinatorial ACT induced stronger infiltration of endogenous CD8+ T cells than Tmem ACT and a stronger systemic T cell responsiveness to tumor antigen. In vitro assays revealed rapid but transient melanoma inhibition with Teff and gradual but prolonged melanoma inhibition with Tmem; the addition of Tmem enhanced the ability of Teff to inhibit melanoma in a manner that could be reproduced using conditioned media from activated Tmem and blocked by the addition of anti-IL-2 blocking antibody. Conclusions These findings suggest that a novel combinatorial approach that takes advantage of the unique and complementary strengths of tumor-specific Teff and Tmem may be a way to optimize the efficacy of adoptive immunotherapy. | |
dc.title | Co-transfer of tumor-specific effector and memory CD8+ T cells enhances the efficacy of adoptive melanoma immunotherapy in a mouse model | |
dc.type | Article | en_US |
dc.description.bitstreamurl | https://deepblue.lib.umich.edu/bitstream/2027.42/143864/1/40425_2018_Article_358.pdf | |
dc.language.rfc3066 | en | |
dc.rights.holder | The Author(s). | |
dc.date.updated | 2018-06-03T04:00:24Z | |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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