Coupling and Uncoupling of Tumor Immunity and Autoimmunity

Bowne, Wilbur B.; Srinivasan, Roopa; Wolchok, Jedd D.; Hawkins, William G.; Blachère, Nathalie E.; Dyall, Ruben; Lewis, Jonathan J.; Houghton, Alan N.

doi:10.1084/jem.190.11.1717

Cited by 218 publications

(191 citation statements)

References 23 publications

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“…In some models, transfer of Treg cells after the onset of disease can even be curative [54]. The close correlation between autoimmunity and tumor immunity [5,7,[55][56][57][58][59] suggests that Treg cells have a crucial role in T-cell tolerance to tumor [60][61][62].…”

Section: Role Of Regulatory Cells In Antitumor Immunitymentioning

confidence: 99%

Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy

Klebanoff

Khong

Antony

et al. 2005

Trends in Immunology

411

288

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Lymphodepletion followed by adoptive cell transfer (ACT) of autologous, tumor-reactive T cells boosts antitumor immunotherapeutic activity in mouse and in humans. In the most recent clinical trials, lymphodepletion together with ACT has an objective response rate of 50% in patients with solid metastatic tumors. The mechanisms underlying this recent advance in cancer immunotherapy are beginning to be elucidated and include: the elimination of cellular cytokine 'sinks' for homeostatic γ C -cytokines, such as interleukin-7 (IL-7), IL-15 and possibly IL-21, which activate and expand tumor-reactive T cells; the impairment of CD4 + CD25 + regulatory T (Treg) cells that suppress tumorreactive T cells; and the induction of tumor apoptosis and necrosis in conjunction with antigenpresenting cell activation. Knowledge of these factors could be exploited therapeutically to improve the in vivo function of adoptively transferred, tumor-reactive T cells for the treatment of cancer.

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Section: Role Of Regulatory Cells In Antitumor Immunitymentioning

confidence: 99%

Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy

Klebanoff

Khong

Antony

et al. 2005

Trends in Immunology

411

288

View full text Add to dashboard Cite

show abstract

“…3, 4). Xenogeneic DNA vaccination has been previously reported to break immunological tolerance in mice with different antigens including HER2, metalloproteainase-2, tyrosinase-related proteins (TRP)-1 and -2, and human gp100 [22][23][24][25]. Different mechanisms can explain the efficacy of this approach, such as the cross-reactivity of conserved peptides which may be recognized differently when presented in a different sequence context.…”

Section: Discussionmentioning

confidence: 99%

Genetic vaccines against Ep‐CAM break tolerance to self in a limited subset of subjects: Initial identification of predictive biomarkers

et al. 2006

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The epithelial cell adhesion molecule, Ep-CAM, has been historically considered a target of passive immunotherapy using monoclonal antibodies, and more recently, of a first Pox-vector-based cancer vaccine Phase I trial in colorectal cancer patients. To shed further light on the use of this antigen, we isolated the mouse and rhesus homologues of human Ep-CAM and explored different genetic vaccination modalities based on the use of adenoviral vectors as well as DNA electroporation (DNA-EP). Immune responses to Ep-CAM were measured by IFN-c ELISPOT and intracellular staining assays using overlapping sets of peptides covering the entire coding regions. We found the most powerful vaccination regimen to be constituted by DNA-EP-prime/Adeno-boost mixedmodality protocols. Vaccination in rhesus macaques resulted in breakage of immunological tolerance in a minority of cases. Similarly, a low frequency of responders was observed with the mouse Ep-CAM vaccine in outbred CD1 mice. When immunized CD1 mice were analyzed for MHC haplotype and TCR expression levels, we observed that immune responders all had the same q/q MHC class I haplotype and showed higher expression levels of the TCRVb4 and TCRVb8 T cell receptors. Our results underscore the current limitations in our capacity to induce efficient cancer vaccines against self antigens like Ep-CAM, but also represent a first effort to identify predictive biomarkers of response.See accompanying commentary: http://dx

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“…One antigen, TRP-2, has displayed promising activity in pre-clinical models. 3,18,19 AdhTRP-2 (5 Â 10 6 pfu/ml) was applied two times to either intact or microporated skin 21 days apart followed by a challenge with B16 Figure 4 Increased magnitude and rate of seroconversion following topical administration of genetic vaccine to microporated skin. Adb-gal (5 Â 10 6 pfu/ml) was applied to both microporated and intact skin.…”

Section: Microporation Can Increase the Activity Of Rdad Vaccines Expmentioning

confidence: 99%

“…Effective immunization against TRP-2 has been correlated with auto-immune reactivity towards normal melanocytes resulting in de-pigmentation of the skin (vitiligo). [18][19][20] Vitiligo has been associated with other melanoma vaccines and may be an unavoidable consequence of effective tumor immunity. 21,22 Interestingly, 13/13 mice vaccinated by application of AdhTRP-2 to microporated skin developed vitiligo at the site of inoculation within 2 weeks following immunization (Figure 9a) whereas no vitiligo was observed following application of AdLuc (0/8) (data not shown).…”

Section: Microporation Can Increase the Activity Of Rdad Vaccines Expmentioning

confidence: 99%

Enabling topical immunization via microporation: a novel method for pain-free and needle-free delivery of adenovirus-based vaccines

et al. 2003

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The skin represents an excellent site for vaccine inoculation due to its natural role as a first line of contact with foreign pathogens and the high local frequency of antigen presenting cells. To facilitate skin-directed immunization, a new technique has been developed (termed microporation) whereby a vaporization process is used to remove tiny areas of the stratum corneum creating microscopic pores that allow access to the underlying viable epidermis. Reporter gene expression was 100-fold increased following application of an adenovirus vector to microporated skin when compared to intact skin. Furthermore, 10-100-fold greater cellular and humoral immune responses were observed following topical administration of an adenovirus vaccine to microporated skin versus intact skin. Hairless mice responded to the microporated adenovirus vaccine equivalently to mice with normal hair follicle distribution demonstrating the activity of the microporated vaccine was not related to follicle count. In a tumor challenge model using a surrogate antigen, microporation increased vaccine efficacy by approximately 100-fold compared to intact skin. Finally, microporation enabled delivery of an adenovirus vaccine carrying a relevant melanoma antigen resulting in the development of autoimmune vitiligo and tumor protection. Thus, the microporation technology has proven to be a reliable and easy method to enable skin-directed vaccination.

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Coupling and Uncoupling of Tumor Immunity and Autoimmunity

Cited by 218 publications

References 23 publications

Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy

Sinks, suppressors and antigen presenters: how lymphodepletion enhances T cell-mediated tumor immunotherapy

Genetic vaccines against Ep‐CAM break tolerance to self in a limited subset of subjects: Initial identification of predictive biomarkers

Enabling topical immunization via microporation: a novel method for pain-free and needle-free delivery of adenovirus-based vaccines

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