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

Abstract

Abstract. 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 [ 3 H]-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 51 Cr-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. IntroductionOvarian cancer (OVCA) remains the leading cause of mortality for patients with gynecologic malignancies, despite recent advances in post-surgical chemotherapy (1). Numerous patients with OVCA are diagnosed at an advanced stage of the disease, but may be treated with surgery followed by chemotherapy. Initially, OVCA may be chemotherapy-sensitive and the majority of patients achieve clinical remission following primary surgical debulking and adjuvant platinum-based therapy. However, the majority of patients who respond to such therapy ultimately succumb due to relapse from recurrent and drug-resistant disease. Following initial treatment, 70-90% of patients relapse. With additional second-line chemotherapy, some patients return to partial or complete remission. However, further relapse is likely to occur (2).Novel therapies that reduce the risk of relapse are therefore urgently required. A variety of systemic and regional consolidation approaches with standard chemotherapy are being investigated. In this context, targeted immunotherapy may be a useful anti-OVCA strategy since such therapy may...

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Therapeutic DC vaccination with IL-2 as a consolidation therapy for ovarian cancer patients: a phase I/II trial

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