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Generation of anti-p53 cytotoxic T lymphocytes from human peripheral blood using autologous dendritic cells.
Clin Cancer Res. 1999 Jun; 5(6):1281-8.CC

Abstract

CTLs recognizing the HLA-A2.1-restricted, wild-type sequence p53 epitopes p53(149-157) and p53(264-272) were generated from CD8-enriched populations of nonadherent peripheral blood lymphocytes (PBLs) obtained from healthy donors. The PBLs were restimulated in vitro with peptide-pulsed granulocyte macrophage colony-stimulating factor- and interleukin (IL)-4-induced autologous dendritic cells in the presence of IL-6 and IL-12 and subsequently cultivated with IL-1alpha, IL-2, IL-4, IL-6, and IL-7. Bulk anti-p53(264-272) CTL populations were generated from PBLs obtained from two of five donors. Both CTL populations were cytotoxic against peptide-pulsed HLA-A2+ target cells, but not against untreated target cells. A CD8+ anti-p53 CTL clone designated p264#2 was isolated from one of the bulk populations. It was found to have an intermediate affinity of approximately 10(-9) M for the epitope and to mediate cytotoxicity against several human tumor cell lines, including the squamous cell carcinoma of the head and neck cell line SCC-9, which is known to present the wild-type sequence p53(264-272) epitope. In addition, CTLs reactive against p53(149-157)-pulsed targets as well as a HLA-A2+ tumor cell line were cloned from a bulk population of antitumor CTLs obtained from one of the five normal PBLs restimulated with this epitope. The results indicate that CTLs recognizing wild-type sequence epitopes can be generated from precursors present in PBLs obtained from some normal individuals using autologous dendritic cells as antigen-presenting cells and suggest that vaccine strategies targeting these epitopes can lead to antitumor CTL generation, thereby emphasizing the therapeutic potential of p53-based cancer vaccines.

Authors+Show Affiliations

University of Pittsburgh Cancer Institute, Pennsylvania 15213, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10389910

Citation

Chikamatsu, K, et al. "Generation of Anti-p53 Cytotoxic T Lymphocytes From Human Peripheral Blood Using Autologous Dendritic Cells." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 5, no. 6, 1999, pp. 1281-8.
Chikamatsu K, Nakano K, Storkus WJ, et al. Generation of anti-p53 cytotoxic T lymphocytes from human peripheral blood using autologous dendritic cells. Clin Cancer Res. 1999;5(6):1281-8.
Chikamatsu, K., Nakano, K., Storkus, W. J., Appella, E., Lotze, M. T., Whiteside, T. L., & DeLeo, A. B. (1999). Generation of anti-p53 cytotoxic T lymphocytes from human peripheral blood using autologous dendritic cells. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 5(6), 1281-8.
Chikamatsu K, et al. Generation of Anti-p53 Cytotoxic T Lymphocytes From Human Peripheral Blood Using Autologous Dendritic Cells. Clin Cancer Res. 1999;5(6):1281-8. PubMed PMID: 10389910.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Generation of anti-p53 cytotoxic T lymphocytes from human peripheral blood using autologous dendritic cells. AU - Chikamatsu,K, AU - Nakano,K, AU - Storkus,W J, AU - Appella,E, AU - Lotze,M T, AU - Whiteside,T L, AU - DeLeo,A B, PY - 1999/7/2/pubmed PY - 1999/7/2/medline PY - 1999/7/2/entrez SP - 1281 EP - 8 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin. Cancer Res. VL - 5 IS - 6 N2 - CTLs recognizing the HLA-A2.1-restricted, wild-type sequence p53 epitopes p53(149-157) and p53(264-272) were generated from CD8-enriched populations of nonadherent peripheral blood lymphocytes (PBLs) obtained from healthy donors. The PBLs were restimulated in vitro with peptide-pulsed granulocyte macrophage colony-stimulating factor- and interleukin (IL)-4-induced autologous dendritic cells in the presence of IL-6 and IL-12 and subsequently cultivated with IL-1alpha, IL-2, IL-4, IL-6, and IL-7. Bulk anti-p53(264-272) CTL populations were generated from PBLs obtained from two of five donors. Both CTL populations were cytotoxic against peptide-pulsed HLA-A2+ target cells, but not against untreated target cells. A CD8+ anti-p53 CTL clone designated p264#2 was isolated from one of the bulk populations. It was found to have an intermediate affinity of approximately 10(-9) M for the epitope and to mediate cytotoxicity against several human tumor cell lines, including the squamous cell carcinoma of the head and neck cell line SCC-9, which is known to present the wild-type sequence p53(264-272) epitope. In addition, CTLs reactive against p53(149-157)-pulsed targets as well as a HLA-A2+ tumor cell line were cloned from a bulk population of antitumor CTLs obtained from one of the five normal PBLs restimulated with this epitope. The results indicate that CTLs recognizing wild-type sequence epitopes can be generated from precursors present in PBLs obtained from some normal individuals using autologous dendritic cells as antigen-presenting cells and suggest that vaccine strategies targeting these epitopes can lead to antitumor CTL generation, thereby emphasizing the therapeutic potential of p53-based cancer vaccines. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/10389910/Generation_of_anti_p53_cytotoxic_T_lymphocytes_from_human_peripheral_blood_using_autologous_dendritic_cells_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=10389910 DB - PRIME DP - Unbound Medicine ER -