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Cancer Immunology, Immunotherapy

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06.03.2018 | Original Article

Rational combinations of in vivo cancer antigen priming and adoptive T-cell therapy mobilize immune and clinical responses in terminal cancers

verfasst von: Qing Zhao Ruan, Jian Qian Fu, Xiao Xuan Wu, Li Ping Huang, Run Sheng Ruan

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 6/2018

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Abstract

Purpose

It is now recognized that solid tumors encroach on the host’s immune microenvironment to favor its own proliferation. Strategies to enhance the specificity of the endogenous T-cell population against tumors have been met with limited clinical success. We aimed to devise a two-tier protocol coupling in vivo whole antigen priming with ex vivo cellular expansion to clinically evaluate survival in patients following re-infusion of primed, autologous T cells, thereby determining treatment efficacy.

Experimental design

Treatment commenced with the acquisition of whole tumor antigens from tumor cell lines corresponding with patients’ primary malignancy. Lysate mixture was inoculated intradermally, while peripheral blood mononuclear cells (PBMCs) were periodically extracted via phlebotomy and expanded in culture ex vivo for re-infusion. Post-treatment tumor-specific T-cell response and cytotoxicity was confirmed via Elispot and real-time cell analyzing (RTCA) assay. Serum cytokine levels and cytotoxicity scores were evaluated for associations with survival status and duration.

Results

There was a significant increase in cytotoxicity exhibited by T cells measured using both Elispot and RTCA following treatment. Correlation analysis determined significant association between higher post-treatment cytotoxicity scores and survival status (R = 0.52, p = 0.0028) as well as longer survival duration in months (R = 0.59, p = 0.005).

Conclusions

Our treatment protocol successfully demonstrated significant correlation between tumor-associated antigen-specific immune response and objective prolongation of survival. Whole-cell cancer antigen priming and adoptive T-cell therapy is, therefore, a highly feasible clinical model which can be easily replicated to positively influence outcome in end-stage malignancy.

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Titel: Rational combinations of in vivo cancer antigen priming and adoptive T-cell therapy mobilize immune and clinical responses in terminal cancers
verfasst von: Qing Zhao Ruan
Jian Qian Fu
Xiao Xuan Wu
Li Ping Huang
Run Sheng Ruan
Publikationsdatum: 06.03.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 6/2018
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-018-2142-z

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