Type I-polarized BRAF-pulsed dendritic cells induce antigen-specific CD8+ T cells that impact BRAF-mutant murine melanoma

Cintolo, Jessica A.; Datta, Jashodeep; Xu, Shuwen; Gupta, Meera; Somasundaram, Rajasekharan; Czerniecki, Brian J.

doi:10.1097/cmr.0000000000000203

Cited by 12 publications

(11 citation statements)

References 67 publications

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“…We anticipate that a variety of derivatives of the lines will be made, including use of CRISPR/Cas9 to evaluate the effects of additional genetic changes, expression of fluorescent proteins to increase the power of intravital imaging techniques, and expression of model antigens in order to more precisely track antigen‐specific immune responses. The YUMM lines have been utilized by numerous investigators prior to this initial description (Bertrand et al., ; Cintolo et al., ; Ho et al., ; Kaur et al., ; Obenauf et al., ; Scortegagna et al., ). The American Type Cell Collection (ATCC) has agreed to distribute 6 of the lines (indicated in Table ).…”

Section: Discussionmentioning

confidence: 99%

The YUMM lines: a series of congenic mouse melanoma cell lines with defined genetic alterations

Meeth

Wang

Micevic

et al. 2016

Pigment Cell Melanoma Res

236

250

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Summary The remarkable success of immune therapies emphasizes the need for immune competent cancer models. Elegant genetically engineered mouse models of a variety of cancers have been established, but their effective use is limited by cost and difficulties in rapidly generating experimental data. Some mouse cancer cell lines are transplantable to immunocompetent host mice and have been utilized extensively to study cancer immunology. Here we describe a comprehensive system of mouse melanoma cell lines that are syngeneic to C57Bl/6J, have well-defined human-relevant driver mutations, and are genomically stable. These will be a useful tool for the study of tumor immunology and genotype-specific cancer biology.

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Section: Discussionmentioning

confidence: 99%

The YUMM lines: a series of congenic mouse melanoma cell lines with defined genetic alterations

Meeth

Wang

Micevic

et al. 2016

Pigment Cell Melanoma Res

236

250

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“…Bone marrow (BM) cells were harvested from femurs and tibias of Balb/C mice as described previously (33). Briefly, BM cells were flushed into a cell suspension in RPMI 1640, and RBCs were lysed using ACK lysing buffer.…”

Section: Methodsmentioning

confidence: 99%

Sequential Anti-PD1 Therapy Following Dendritic Cell Vaccination Improves Survival in a HER2 Mammary Carcinoma Model and Identifies a Critical Role for CD4 T Cells in Mediating the Response

et al. 2019

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Patients with metastatic HER2 breast cancer (MBC) often become resistant to HER 2 targeted therapy and have recurrence of disease. The Panacea trial suggested that HER2 MBC patients were more likely to respond to checkpoint therapy if TIL were present or if tumor expressed PD-L1. We assessed whether type I polarized dendritic cells (DC1) could improve checkpoint therapy in a preclinical model of HER2 + breast cancer. TUBO bearing mice were vaccinated with either MHC class I or class II HER2 peptide pulsed DC1 (class I or class II HER2-DC1) concurrently or sequentially with administration of anti-PD-1 or anti-PDL1. Infiltration of tumors by immune cells, induction of anti-HER2 immunity and response to therapy was evaluated. Class I or class II HER2-DC1 vaccinated mice generated anti-HER2 CD8 or CD4+ T cell immune responses and demonstrated delayed tumor growth. Combining both MHC class I and II HER2-pulsed DC1 did not further result in inhibition of tumor growth or enhanced survival compared to individual administration. Interestingly class II HER2-DC1 led to both increased CD4 and CD8 T cells in the tumor microenvironment while class I peptides typically resulted in only increased CD8 T cells. Anti-PD-1 but not anti-PD-L1 administered sequentially with class I or class II HER2-DC1 vaccine could improve the efficacy of HER2-DC1 vaccine as measured by tumor growth, survival, infiltration of tumors by T cells and increase in systemic anti-HER2 immune responses. Depletion of CD4+ T cells abrogated the anti-tumor efficacy of combination therapy with class II HER2-DC1 and anti-PD-1, suggesting that tumor regression was CD4 dependent. Since class II HER2-DC1 was as effective as class I, we combined class II HER2-DC1 vaccine with anti-rat neu antibodies and anti-PD-1 therapy. Combination therapy demonstrated further delay in tumor growth, and enhanced survival compared to control mice. In summary, Class II HER2-DC1 drives both a CD4 and CD8 T cell tumor infiltration that leads to increased survival, and in combination with anti-HER2 therapy and checkpoint blockade can improve survival in preclinical models of HER2 positive breast cancer and warrants exploration in patients with HER2 MBC.

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“…BRAF, KIT, and NRAS mutations are common mutated antigens in melanoma. Antigenic BRAF peptides encompassing the V600E driver mutation of melanoma have been reported [7][8][9][10] , inducing BRAF-specific immune responses in humans 9,10 and tumor control in mice 7,8 . These data support further clinical investigation of these mutated antigens in vaccines.…”

Section: Shared Melanoma Antigensmentioning

confidence: 99%

Vaccine Strategy in Melanoma

Kwak¹,

Slingluff²,

Melssen³

2019

Surgical Oncology Clinics of North America

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The incidence of melanoma continues to increase even as advances in immunotherapy have led to survival benefits in advanced stages. Vaccines are capable of inducing strong, anti-tumor immune responses with limited toxicity. Some vaccines have demonstrated clinical benefit in clinical trials alone; however, others have not despite inducing strong immune responses. Recent advancements have improved vaccine design, while combining vaccines with other immunotherapies offers promise. This review highlights the underlying principles of vaccine development, common components of vaccines, the remaining challenges and future directions of vaccine therapy in melanoma.

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Type I-polarized BRAF-pulsed dendritic cells induce antigen-specific CD8+ T cells that impact BRAF-mutant murine melanoma

Cited by 12 publications

References 67 publications

The YUMM lines: a series of congenic mouse melanoma cell lines with defined genetic alterations

The YUMM lines: a series of congenic mouse melanoma cell lines with defined genetic alterations

Sequential Anti-PD1 Therapy Following Dendritic Cell Vaccination Improves Survival in a HER2 Mammary Carcinoma Model and Identifies a Critical Role for CD4 T Cells in Mediating the Response

Vaccine Strategy in Melanoma

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