Enhanced local and systemic anti-melanoma CD8+ T cell responses after memory T cell-based adoptive immunotherapy in mice

Contreras, Amanda; Sen, Siddhartha; Tatar, Andrew J.; Mahvi, David A.; Meyers, Justin V.; Srinand, Prakrithi; Suresh, M.; Cho, Clifford S.

doi:10.1007/s00262-016-1823-8

Cited by 13 publications

(18 citation statements)

References 52 publications

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“…Viral infections and tumor inoculations were performed per our previously published protocols [ 7 , 9 , 10 ]. In brief, Ly5.1+/C57BL/6 mice were infected with 2 × 10 5 PFU of Armstrong strain lymphocytic choriomeningitis virus (LCMV; gift from Marulasiddappa Suresh, University of Wisconsin) via intraperitoneal injection to generate CD8+ T cells specific for GP33, a class I MHC-restricted LCMV surface glycoprotein.…”

Section: Methodsmentioning

confidence: 99%

“…Less-differentiated effector cells have been shown to have superior antitumor immunity compared to terminally-differentiated cells, potentially due to a number of mechanisms such as decreased IL-2 production and increased apoptosis with further differentiation [ 4 , 5 ]. Our laboratory and others have also demonstrated that ACT with T mem is more effective than ACT with T eff or naïve T cells [ 6 , 7 ]. T mem appear to be uniquely resistant to melanoma-induced suppression and generate a stronger intratumoral immune response [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…Our laboratory and others have also demonstrated that ACT with T mem is more effective than ACT with T eff or naïve T cells [ 6 , 7 ]. T mem appear to be uniquely resistant to melanoma-induced suppression and generate a stronger intratumoral immune response [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Co-transfer of tumor-specific effector and memory CD8+ T cells enhances the efficacy of adoptive melanoma immunotherapy in a mouse model

Contreras¹,

Beems²,

Tatar³

et al. 2018

j. immunotherapy cancer

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BackgroundAdoptive 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.MethodsSplenocytes 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.ResultsInhibition 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.ConclusionsThese 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.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Co-transfer of tumor-specific effector and memory CD8+ T cells enhances the efficacy of adoptive melanoma immunotherapy in a mouse model

Contreras¹,

Beems²,

Tatar³

et al. 2018

j. immunotherapy cancer

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“…Extraction of T cells from patients and the subsequent genetic modification of these cells with chimeric antigen receptors are under development as a promising alternative approach. Contreras et al [ 15 ] inoculated B16F10 melanoma cells that express very low levels of the lymphocytic choriomeningitis virus peptide GP33 (B16GP33) into syngeneic C57BL/6 mice. Subsequently, bona fide, naïve, effector, or memory phenotype GP33-specific CD8 + T cells were adoptively transferred into the mice after inoculation.…”

Section: Immunotherapy Approachesmentioning

confidence: 99%

Advances in Immunotherapy for Melanoma: A Comprehensive Review

Rodríguez-Cerdeira

Carnero-Gregorio

López-Bárcenas

et al. 2017

Mediators of Inflammation

101

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Melanomas are tumors originating from melanocytes and tend to show early metastasis secondary to the loss of cellular adhesion in the primary tumor, resulting in high mortality rates. Cancer-specific active immunotherapy is an experimental form of treatment that stimulates the immune system to recognize antigens on the surface of cancer cells. Current experimental approaches in immunotherapy include vaccines, biochemotherapy, and the transfer of adoptive T cells and dendritic cells. Several types of vaccines, including peptide, viral, and dendritic cell vaccines, are currently under investigation for the treatment of melanoma. These treatments have the same goal as drugs that are already used to stimulate the proliferation of T lymphocytes in order to destroy tumor cells; however, immunotherapies aim to selectively attack the tumor cells of each patient. In this comprehensive review, we describe recent advancements in the development of immunotherapies for melanoma, with a specific focus on the identification of neoantigens for the prediction of their elicited immune responses. This review is expected to provide important insights into the future of immunotherapy for melanoma.

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“…Traditional ACT protocols exploit the antigen-specific cytolytic potential of CD8 + T cells by transferring terminally differentiated effector T (T EFF ) cells, but more recent evidence has shown that less differentiated cells, such as central memory T (T CM ) cells, show superior performance (14,15). Therefore, in this study, we used an immunotherapy platform that combines adoptive transfer of tumor-reactive T CM cells with oncolytic virus vaccines (OVVs).…”

Section: Introductionmentioning

confidence: 99%

Type I IFN blockade uncouples immunotherapy-induced antitumor immunity and autoimmune toxicity

Walsh

Bastin

Chen

et al. 2018

Journal of Clinical Investigation

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Enhanced local and systemic anti-melanoma CD8+ T cell responses after memory T cell-based adoptive immunotherapy in mice

Cited by 13 publications

References 52 publications

Co-transfer of tumor-specific effector and memory CD8+ T cells enhances the efficacy of adoptive melanoma immunotherapy in a mouse model

Co-transfer of tumor-specific effector and memory CD8+ T cells enhances the efficacy of adoptive melanoma immunotherapy in a mouse model

Advances in Immunotherapy for Melanoma: A Comprehensive Review

Type I IFN blockade uncouples immunotherapy-induced antitumor immunity and autoimmune toxicity

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