Anticancer immune reactivity and long-term survival after treatment of metastatic ovarian cancer with dendritic cells

Hematopoietic stem cells collected by leukapheresis of a patient with metastatic ovarian carcinoma (OVCA) were induced into dendritic cell (DC) differentiation and fused with liposomal constructs of autologous and allogeneic ovarian carcinoma antigens (DC-OVCA). The proliferation of autologous T cel...

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Bibliographic Details
Published in:	Oncology letters Vol. 3; no. 1; pp. 66 - 74
Main Authors:	BERNAL, SAMUEL D, ONA, ENRIQUE T, RIEGO-JAVIER, AILEEN, DE VILLA, ROMULO, CRISTAL-LUNA, GLORIA R, LAGUATAN, JOSEPHINE B, BATAC, EUNICE R, CANLAS, OSCAR Q
Format:	Journal Article
Language:	English
Published:	Greece D.A. Spandidos 01-01-2012
Subjects:	anticancer cancer cancer treatment dendritic cells immune reactivity long-term survival metastatic ovarian cancer ovarian cancer regenerative medicine
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Summary:	Hematopoietic stem cells collected by leukapheresis of a patient with metastatic ovarian carcinoma (OVCA) were induced into dendritic cell (DC) differentiation and fused with liposomal constructs of autologous and allogeneic ovarian carcinoma antigens (DC-OVCA). The proliferation of autologous T cells induced by DCs was determined by [3H]-thymidine uptake. Maximal T-cell proliferation was observed in co-cultures of DCs fused with liposomal OVCA constructs compared with intact autologous OVCA cells. The combination of autologous and allogeneic liposomal OVCA constructs induced greater T-cell proliferation than either alone. The cytotoxicity of DC-activated T cells against various target cells were analyzed by a 51Cr-release assay. The combination of autologous and allogeneic liposomal OVCA constructs showed the highest stimulation of T cell-mediated cytotoxicity against OVCA cells, but had minimal cytotoxicity against normal fibroblasts or leukemia cells. The liposomal preparations of DC-OVCA were injected monthly into a patient with metastatic ovarian carcinoma whose tumors progressed following multiple courses of chemotherapy. DCs analyzed from the patient post-immunization showed 2- to 3-fold greater OVCA cytotoxicity compared to pre-immunization DCs. Immunoblots using the patient's serum showed reactivity with a number of proteins from ovarian cancer extracts, but not in normal fibroblasts and breast cancer. Following the DC-OVCA treatment, the metastatic lesions progressively decreased in size to the point of being undetectable by serial CAT scans. Seven years following the initial diagnosis, the patient continues to be free of cancer. This report described the anticancer immune reactivity and anti-tumor response induced by DCs sensitized with liposomal constructs of OVCA antigens. Immune cell therapy may therefore be a useful adjunct to surgery and chemotherapy for the treatment of ovarian cancer.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1792-1074 1792-1082
DOI:	10.3892/ol.2011.424