N-Terminally LRMK-linked HER-2 peptides, AE-37 [p776(774-788)] and AE-47 [Ava-F7(776-788)], Aid Differentiation of E75-TCR(+)CD8(+) Cells to Perforin-positive Cells

Matsueda, S; Gao, H; Efferson, CL; Tsuda, N; Ishiyama, S; Li, YF; Ioannides, MG; Fisk, B; Peoples, GE; Ioannides, CG

dc.contributor.author	Matsueda, S	en
dc.contributor.author	Gao, H	en
dc.contributor.author	Efferson, CL	en
dc.contributor.author	Tsuda, N	en
dc.contributor.author	Ishiyama, S	en
dc.contributor.author	Li, YF	en
dc.contributor.author	Ioannides, MG	en
dc.contributor.author	Fisk, B	en
dc.contributor.author	Peoples, GE	en
dc.contributor.author	Ioannides, CG	en
dc.date.accessioned	2014-03-01T01:58:56Z
dc.date.available	2014-03-01T01:58:56Z
dc.date.issued	2009	en
dc.identifier.issn	0250-7005	en
dc.identifier.uri	https://dspace.lib.ntua.gr/xmlui/handle/123456789/28783
dc.subject	HER-2	en
dc.subject	helper effect	en
dc.subject	AE-37	en
dc.subject	AE-47	en
dc.subject	p776	en
dc.subject	F7	en
dc.subject	perforin	en
dc.subject	E75	en
dc.subject	cancer vaccines	en
dc.subject	high-affinity CD8(+) cells	en
dc.subject.classification	Oncology	en
dc.subject.other	BREAST-CANCER PATIENTS	en
dc.subject.other	CLASS-II MOLECULES	en
dc.subject.other	INVARIANT CHAIN	en
dc.subject.other	CLINICAL-TRIAL	en
dc.subject.other	LYMPH-NODE	en
dc.subject.other	RESPONSES	en
dc.subject.other	EPITOPES	en
dc.subject.other	VACCINES	en
dc.subject.other	COMPLEX	en
dc.subject.other	TUMOR	en
dc.title	N-Terminally LRMK-linked HER-2 peptides, AE-37 [p776(774-788)] and AE-47 [Ava-F7(776-788)], Aid Differentiation of E75-TCR(+)CD8(+) Cells to Perforin-positive Cells	en
heal.type	journalArticle	en
heal.language	English	en
heal.publicationDate	2009	en
heal.abstract	The objective of this study was to discover whether the peptides LRMK and LRMK-Ava linked to the N-terminus of peptides HER-2 (774-788) and HER-2 (776788), respectively, help differentiation of E75-TCR(+)CD8(+) cells. Activation was quantified in terms of proliferation of E75-TCR(+)CD8(+) cells expressing high, medium and low density amounts of the specific TCR. Differentiation to functional CD8(+) cells was quantified as induction of Perforin (Perf), the lytic-enzyme which mediates the effector function of CD8(+) cells, in E75-TCR(+)CD8(+) cells. Peripheral blood mononuclear cells (PBMCs) of 3 patients activated with E75(+)AE-37 and E75(+)AE-47 more greatly increased the number of E75-TCRHi CD8(+)Perf(+) cells than PBMCs activated by AE-47 alone or AE-47(+) E75. E75 plus cytokines and cytokines alone activated more E75-TCRLow cells than did AE-37 and AE-47. E75(+) AE-37 and AE-37 also induced differentiation of small- and medium-size activated CD8(+) cells from BRC ascites, in allogeneic activation, to Perf(+) cells. Preferential differentiation of E75-TCR(+)CD8(+)Perf(+) cells in distinct patients by AE-37 and AE-47 indicates that cancer vaccines will benefit from such correct individual and disease-associated help. Additional studies using the natural peptides p776 and F7 are needed to understand whether the LRMK-(Ava) tetra-, or pentamer augments or inhibits differentiation of CD8(+) cells, compared with native, natural HER-2 peptides and/or protects CD8(+) cells activated by E75 and by other HLA-I bound peptides from death. Our findings also develop a model for uniform quantification of differentiated CD8(+) effectors.	en
heal.publisher	INT INST ANTICANCER RESEARCH	en
heal.journalName	ANTICANCER RESEARCH	en
dc.identifier.isi	ISI:000268104100002	en
dc.identifier.volume	29	en
dc.identifier.issue	7	en
dc.identifier.spage	2427	en
dc.identifier.epage	2435	en