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Personalized polyvalent DC vaccine pulsed with various long overlapped peptide antigens - a pilot study in patients with intractable non-small cell lung cancer (NSLC).

2017/05/12

Abe H1), 2) , Abe M2)

 

1) Abe Cancer Clinic

2) Life Science Research Institute

 

Abstract

 

Back ground:

Dendritic cells (DCs) play a critical role in both the innate and adaptive immune response. DCs can act as antigen-presenting cells (APCs) by a peptide antigen and major histocompatibility complex (MHC). And then, these molecules activate peptide antigen-specific cytotoxic T lymphocytes (CTLs) that then eliminate cancer cells. However, cancer cells have diversity characteristics and escape immune attacks which cause recurrence and metastatic outcome.

 

Method:

In order to solve the above mentioned problems, in vitro proliferation of monocytes isolated from 20-25ml of peripheral blood by negative magnetic bead selection is proposed. It was found that various cytokines involved in Flt-3L. A monocyte proliferating agent is consisting of GM-CSF and Flt-3L and being used before treatment for differentiating monocytes into imDCs and mDCs. The culture medium for use in the proliferation of a monocyte contains GM-CSF. After sufficient monocytes obtained, DC vaccine is prepared according to conventional way. Especially, DCs are pulsed with multiple polyvalent peptides.

In pilot study, twenty-two patients with stage IV non-small cell lung cancer (NSCL) after conventional therapy were entered. DC vaccine is injected every 2 weeks totally 5 times.

 

Result:

In this way, we investigated that activation of CTLs by our monocyte-derived DCs pulsed with various and polyvalent peptide antigen by ELISPOT assay. As results, activation of various peptide-specific CTL was detected by this assay. In addition, some of peptide antigens such as WT1 and MUC1 stimulated DC4+ and CD8+ T cells via both MHC class I and II.

Among 22 patients intractable NSCL, 2 patients showed CR, 3 showed PR, 10 showed SD and 7 showed PD. Overall survival curve up to 1,000 days were shown.


Biomarkers & Immuno-onclology World Congress 2017

May 2 - 4, 2017, Philadelphia, USA



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