An Effective Vaccine Strategy Protective against Antigenically Distinct Tumor Variants

Pavelko, Kevin D.; Heckman, Karin L.; Hansen, Michael J.; Pease, Larry R.

doi:10.1158/0008-5472.can-07-5937

Cited by 11 publications

(14 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2 A ). Consistent with previous findings (15), immunization with B16-CL and immune modulating B7-DCXAb generated a broader response, targeting TRP1 7 , TRP1 175 , TRP1 222 and TRP1 396 .…”

Section: Resultssupporting

confidence: 90%

“…B7-DCXAb given one day before B16 challenge or with B16-CL as a vaccine generates CTL that target and eliminate B16 melanoma (15). To learn which antigens are targeted by these vaccines, we used peptide pulsed targets to screen MHC class I epitopes identified in B16 models (1, 2, 19, 20).…”

Section: Resultsmentioning

confidence: 99%

“…TRP1 can be secreted (29), possibly gaining access to the lymph node faster than cell associated antigens. We previously identified biochemical differences in recognized antigens derived from live tumors versus tumor lysates (15), suggesting that negatively charged moieties, consistent with mature sialylated TRP1 molecules, may be targeted more efficiently after challenge with live tumor cells. Importantly, native TRP1 is processed and cross-presented by DC in a manner promoting the activation of CD8+ T cells specific for this low affinity MHC class I ligand.…”

Section: Discussionmentioning

confidence: 99%

“…ODN-1826 (5′TCCATGACGTTCCTGACGTT 3′) (CpG) was synthesized by the Mayo Clinic Advanced Genomics Technology Center. B16 cell lysate (B16-CL) was prepared as described (15). …”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

CTL Activation Using the Natural Low-Affinity Epitope 222-229 from Tyrosinase-Related Protein 1 Leads to Tumor Rejection

2009

Self Cite

View full text Add to dashboard Cite

Vaccine strategies for cancer immunotherapy have focused on peptide ligands with high affinity for MHC class I. Largely, these vaccines have not been therapeutic. We have examined the peptide specificity of a strongly protective T cell response which eradicates established B16 melanoma and find that the recognized epitope is generated by a low affinity MHC class I ligand from tyrosinase related protein 1 (TRP1). Cytotoxic T cell responses are induced against TRP1222-229 by several vaccination schemes using toll-like receptor agonist, T regulatory cell depletion, or the immune modulator B7-DCXAb to drive immunity. TRP1222 CTL are generated from multiple antigen sources, including antigens expressed by tumors growing in situ, tumor cell lysates, and peptide vaccines. The key finding in this study is that protection from freshly implanted or established B16 tumors is mediated primarily by TRP1222-specific CTL and not by CTL specific for more traditional melanoma antigens such as TRP2 or gp100. This finding challenges the assumption that the optimal peptide antigens for cancer vaccines are high affinity MHC ligands. We propose that when administered appropriately, native low affinity MHC ligands are optimal inducers of immunotherapeutic CTL.

show abstract

“…2 A ). Consistent with previous findings (15), immunization with B16-CL and immune modulating B7-DCXAb generated a broader response, targeting TRP1 7 , TRP1 175 , TRP1 222 and TRP1 396 .…”

Section: Resultssupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…ODN-1826 (5′TCCATGACGTTCCTGACGTT 3′) (CpG) was synthesized by the Mayo Clinic Advanced Genomics Technology Center. B16 cell lysate (B16-CL) was prepared as described (15). …”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

CTL Activation Using the Natural Low-Affinity Epitope 222-229 from Tyrosinase-Related Protein 1 Leads to Tumor Rejection

2009

Self Cite

View full text Add to dashboard Cite

show abstract

“…At the same time, there is a rapid mobilization of antigen specific CD8 cytolytic cells that are also antigen-specific (33). The net change resulting in the loss of down modulatory effects of the Tregs and the alignment of the polarity of helper T cells with the activated CTL can result in an effective anti-tumor response that can clear transplanted tumors (22, 59). …”

Section: Discussionmentioning

confidence: 99%

Reprogrammed FoxP3+ T Regulatory Cells Become IL-17+ Antigen-Specific Autoimmune Effectors In Vitro and In Vivo

Radhakrishnan

Cabrera

Schenk

et al. 2008

The Journal of Immunology

Self Cite

105

View full text Add to dashboard Cite

Lymphocyte differentiation from naive CD4+ T cells into mature Th1, Th2, Th17, or T regulatory cell (Treg) phenotypes has been considered end stage in character. In this study, we demonstrate that dendritic cells (DCs) activated with a novel immune modulator B7-DC XAb (DCXAb) can reprogram Tregs into T effector cells. Down-regulation of FoxP3 expression after either in vitro or in vivo Treg-DCXAb interaction is Ag-specific, IL-6-dependent, and results in the functional reprogramming of the mature T cell phenotype. The reprogrammed Tregs cease to express IL-10 and TGFβ, fail to suppress T cell responses, and gain the ability to produce IFN-γ, IL-17, and TNF-α. The ability of IL-6+ DCXAb and the inability of IL-6−/− DCXAb vaccines to protect animals from lethal melanoma suggest that exogenously modulated DC can reprogram host Tregs. In support of this hypothesis and as a test for Ag specificity, transfer of DCXAb into RIP-OVA mice causes a break in immune tolerance, inducing diabetes. Conversely, adoptive transfer of reprogrammed Tregs but not similarly treated CD25− T cells into naive RIP-OVA mice is also sufficient to cause autoimmune diabetes. Yet, treatment of normal mice with B7-DC XAb fails to elicit generalized autoimmunity. The finding that mature Tregs can be reprogrammed into competent effector cells provides new insights into the plasticity of T cell lineage, underscores the importance of DC-T cell interaction in balancing immunity with tolerance, points to Tregs as a reservoir of autoimmune effectors, and defines a new approach for breaking tolerance to self Ags as a strategy for cancer immunotherapy.

show abstract

Shikonin induces immunogenic cell death in tumor cells and enhances dendritic cell-based cancer vaccine

Chen

Wang

Chen

et al. 2012

Cancer Immunol Immunother

112

118

View full text Add to dashboard Cite

Immunogenic cell death is characterized by damage-associated molecular patterns, which can enhance the maturation and antigen uptake of dendritic cells. Shikonin, an anti-inflammatory and antitumor phytochemical, was exploited here as an adjuvant for dendritic cell-based cancer vaccines via induction of immunogenic cell death. Shikonin can effectively activate both receptor- and mitochondria-mediated apoptosis and increase the expression of all five tested damage-associated molecular patterns in the resultant tumor cell lysates. The combination treatment with damage-associated molecular patterns and LPS activates dendritic cells to a high maturation status and enhances the priming of Th1/Th17 effector cells. Shikonin-tumor cell lysate-loaded mature dendritic cells exhibit a high level of CD86 and MHC class II and activate Th1 cells. The shikonin-tumor cell lysate-loaded dendritic cell vaccines result in a strong induction of cytotoxic activity of splenocytes against target tumor cells, a retardation in tumor growth, and an increase in the survival of test mice. The much enhanced immunogenicity and efficacy of the current cancer vaccine formulation, that is, the use of shikonin-treated tumor cells as cell lysates for the pulse of dendritic cells in culture, may suggest a new ex vivo approach for developing individualized, dendritic cells-based anticancer vaccines.

show abstract

An Effective Vaccine Strategy Protective against Antigenically Distinct Tumor Variants

Cited by 11 publications

References 25 publications

CTL Activation Using the Natural Low-Affinity Epitope 222-229 from Tyrosinase-Related Protein 1 Leads to Tumor Rejection

CTL Activation Using the Natural Low-Affinity Epitope 222-229 from Tyrosinase-Related Protein 1 Leads to Tumor Rejection

Reprogrammed FoxP3+ T Regulatory Cells Become IL-17+ Antigen-Specific Autoimmune Effectors In Vitro and In Vivo

Shikonin induces immunogenic cell death in tumor cells and enhances dendritic cell-based cancer vaccine

Contact Info

Product

Resources

About