摘要:

Summary:This article reports on the first double-blind randomized clinical study with an antiidiotype antibody vaccine in patients with metastatic colorectal carcinoma. The study was performed to determine immunological parameters, efficacy, and tolerability of the vaccine. Forty-two patients with metastatic colorectal cancer were randomly assigned to multiple immunizations with goat IgG antiidiotype vaccine SCV 106 (n=21) or unspecific goat IgG as controls (n=21). The antiidiotype vaccine mimicked the 17-1A glycoprotein antigen associated with colorectal cancer. Of the 42 patients entered, 39 were evaluable for efficacy (SCV 106, n=18; controls, n=21). Twenty-nine patients raised antibodies to the vaccines (immunological responders, SCV 106, n=12; controls, n=17). Only in the SCV 106 group was a significant increase (p=0.002) of titers with specificity of antitumor antibody 17-1A found. According to the International Union Against Cancer (UICC) criteria no tumor response was observed. However, in the SCV 106 group the relative increase of carcinoembryonic antigen (CEA) levels between entry and observed disease progression was lower (p=0.03) and disease progression was determined less frequently by development of new metastases (p=0.001). On an intention-to-treat basis, the survival time difference between the two groups was not significant. Comparison of immunological responders in both groups revealed a significant survival advantage of the SCV 106-treated patients compared with controls (mean 67 versus 39 weeks; p=0.01). Immunizations were well tolerated. Vaccination of immunologically responding metastatic colorectal carcinoma patients with SCV 106 leads to slowed disease progression and tumor dissemination and significantly prolongs survival time.

ISSN:1524-9557    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Summary:Interleukin-10 (IL-10) has a wide range of in vivo biological activities and is a key regulatory cytokine of immune-mediated inflammation. The authors found that murine IL-10 given 12 hours after a recombinant vaccinia virus (rVV) containing theLacZgene significantly enhanced the treatment of mice bearing 3-day-old pulmonary metastases expressing β-galactosidase. Because IL-10 has been shown to inhibit the functions of key elements of both innate and acquired immune responses, the authors hypothesized that IL-10 might act by inhibiting clearance of the rVV, thus prolonging exposure to the experimental antigen. However, evidence that IL-10 was not acting primarily through such negative regulatory mechanisms included the following: (a) IL-10 also enhanced the therapeutic effectiveness of a recombinant fowlpox virus, which cannot replicate in mammalian cells; (b) Titers of rVV in immunized mice were lower, not higher; and (c) Although IL-10 did not alter levels of anti-vaccinia antibodies or natural killer cell activity, rVV-primed mice treated with IL-10 had enhanced vaccinia-specific cytotoxic T-lymphocyte activity. Thus, IL-10 enhanced the function of a recombinant poxvirus-based anti-cancer vaccine and may represent a potential adjuvant in the vaccination against human cancers using recombinant poxvirus-based vaccines.

ISSN:1524-9557    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Summary:Naturally occurring malignancies do not induce immune responses against cancer antigens. Is the lack of an immune response caused by an antigen presentation defect or by induced antigen-specific immune suppression? The current study was performed to determine whether a progressing intracerebral malignancy affects production of peripheral autologous glioma antigen-specific immune responses. Peripheral immunization of both glioma-bearing and non-glioma-bearing animals with cancer cells and adjuvant generated similar levels of glioma antigen-specific cytotoxic T lymphocyte activity. However, immune cell populations from glioma bearers were significantly less efficient than immune cell populations from non-cancer bearers in their ability to reject progressing intracerebral tumors. A variety of manipulations designed to reduce nonspecific immune suppression in vivo and in vitro had no effect on the in vivo efficacy of the activated T-lymphocyte populations. The presence of progressing tumors appeared to augment rather than suppress cancer antigen-specific responses, leading to the speculation that reduced efficacy was caused not by generalized immune suppression but rather by a reduction in the number of immune effector cells by either clonal anergy or clonal deletion. Most importantly, the data demonstrated that, despite decreased in vivo efficacy, immune effector cells capable of rejecting an intracerebral malignancy could be generated from cancerous hosts.

ISSN:1524-9557    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Summary:Clinical trials of active immunotherapy strategies against viral infections and malignancies are increasingly using dendritic cells (DC) generated in vitro from peripheral blood mononuclear cells (PBMC) in media supplemented with granulocyte macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4). Although GM-CSF appears necessary, it is not well established whether other cytokines have advantages or could replace IL-4 in clinical preparations. IL-13 is a Th2-derived cytokine that shares a variety of biologic functions with IL-4, such as inhibition of monocyte differentiation and upregulation of major histocompatibility complex (MHC) molecules on cell surfaces. In the present study, the authors compared IL-4 and IL-13 in their abilities to induce DC differentiation and found that adherent PBMC cultured in GM-CSF and IL-13 displayed features characteristic of DC generated in media containing IL-4. They formed cellular clumps and had extensive dendrites. Fluorescence-activated cell sorter analysis showed that they expressed a high level of MHC class II and the costimulatory molecule CD86, and did not express the lineage markers CD3, CD14, CD16, or CD20. They were also equally potent stimulators of allogeneic lymphocytes in the mixed lymphocyte reaction. Moreover, the authors demonstrated that they were capable of inducing antigen-specific CD8+ cytotoxic T cells efficiently.

ISSN:1524-9557    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Summary:Bispecific monoclonal antibodies (BiMAb) have been shown to be able to contribute to an immunological approach in cancer therapy. In this review, essential aspects regarding the production of BiMAb and modes to apply them in immunotherapy for cancer are discussed. The pros and cons of BiMAb are considered, and the development from application in animal models to clinical studies is reviewed. The most important clinical trials are summarized, and the different problems encountered are discussed. Provided some crucial problems can be overcome, BiMAb will have a place in the treatment of cancer, especially in the setting of minimal residual disease.

ISSN:1524-9557    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Summary:In an attempt to mimic cytokine gene-transfected tumor cells and to develop an alternative approach to cancer immunotherapy, the authors vaccinated mice with mixtures of inactivated tumor cells and cytokine-containing depots. The RenCa mouse renal carcinoma and the B16 mouse melanoma were used as animal tumor models, with interleukin-2 (IL-2) as a cytokine and liposomes as a depot form. The results obtained show that vaccines consisting of mixtures of irradiated tumor cells and cytokine-containing liposomes can be used as highly effective tumor vaccines. These vaccines are very easy to prepare and, in contrast to vaccines consisting of cytokine gene transfected tumor cells, their composition (cell dosage, cytokine dosage) can be easily varied. Vaccination efficiency depended on (a) on the immunogenicity of the tumor cells: RenCa tumor cells are more immunogenic than B16 melanoma cells; (b) vaccination frequency: a single vaccination with irradiated tumor cells and 10 (xg of IL-2 in liposome-encapsulated form was sufficient to induce lasting protective immunity against the RenCa tumor, whereas several (four to six) vaccinations in weekly intervals were needed to obtain a similar degree of protective immunity to the B16 melanoma; and (c) the dose of the cytokine encapsulated in the admixed liposome depots: immunity to the tumors could be induced only within a narrow cytokine-dose range (“IL-2-dose window”). The results obtained indicate that, because of the easiness of preparation and handling, vaccine formulations consisting of irradiated tumor cells and IL-2 in depot formulations are candidates for tumor vaccines for the treatment of tumor patients.

ISSN:1524-9557    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Summary:The efficacy, safety, and optimum clinical dose of recombinant human interleukin-3 (rhIL-3) was examined in ovarian cancer patients with thrombocytopenia after cancer chemotherapy. In cases with a platelet count

ISSN:1524-9557    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:1524-9557    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:1524-9557    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Summary:Recombinant receptors with antibody-like specificity for tumor-associated antigens were shown to direct specifically T cells to target tumor cells. Hodgkin and Reed-Sternberg cells, the malignant cell population in Hodgkin's lymphoma, express high amounts of the cell surface antigen CD30. An anti-CD30 T-cell receptor with cellular activation properties is expected to graft T cells with specificity to Hodgkin cells. Here, the authors characterize a chimeric T-cell receptor with an extracellular domain consisting of the single-chain antibody fragment HRS3-scFv with specificity for the CD30 antigen and intracellular domain of the signal transducing part of the Fc-epsilon-I-gamma receptor. The HRS3-scFv was derived from the monoclonal anti- CD30 antibody HRS3 and retained specificity for the CD30 antigen. The recombinant HRS3-scFv-gamma receptor was expressed under control of the RS V-LTR after transfection into MD45 T-cells. The chimeric receptor protein is detected and analyzed by enzyme-linked immunosorbent assay (ELISA) and immunoprecipitation. Expression of the chimeric receptor converts MD45 T cells to specificity for CD30+ lymphoma cells. Specific cross-linking of the chimeric receptor with antigen resulted in cytolytic reactivity against CD30+ tumor cells in vitro. The results demonstrate that the chimeric receptor HRS3-scFv-gamma converts T cells to a specific MHC-unrestricted cytolytic response against CD30+ tumor cells offering an alternative strategy in cellular immunotherapy of Hodgkin's disease.

ISSN:1524-9557    

出版商:OVID    

年代:1999

数据来源: OVID