Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High-dose chemotherapy with peripheral blood progenitor cell transplantation (PBPCT) is a potentially curative treatment option for patients with both hematological malignancies and solid tumors, including breast cancer. However, based on a number of clinical studies, there is strong evidence that minimal residual disease (MRD) persists after high-dose chemotherapy in a number of patients, which eventually results in disease recurrence. Therefore, several approaches to the treatment of MRD are currently being evaluated, including treatment with dendritic cell (DC)-based cancer vaccines. DCs, which play a crucial role with regard to the initiation of T-lymphocyte responses, can be generated ex vivo either from CD34+ hematopoietic progenitor cells or from blood monocytes. They can be pulsed in vitro with tumor-derived peptides or proteins, and then used as a professional antigen-presenting cell (APC) vaccine for the induction of antigen-specific T-lymphocytes in vivo. This paper summarizes our preclinical studies on the induction of primary HER-2/neu specific cytotoxic T-lymphocyte (CTL) responses using peptide-pulsed DC. As HER-2/neu is overexpressed on 30-40% of breast and ovarian cancer cells, this novel vaccination approach might be particularly applicable to advanced breast or ovarian cancer patients after high-dose chemotherapy and autologous PBPCT.
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PMID:Approaches to dendritic cell-based immunotherapy after peripheral blood stem cell transplantation. 1037 38

Immunomodulatory strategies, such as antibody therapy and cancer vaccines, are increasingly being considered as potential adjuvant therapies in patients with advanced stage breast cancer to either treat minimal residual disease or prevent relapse. However, little is known concerning the incidence and magnitude of the pre-existent breast cancer specific immune response in this patient population. Using the HER-2/neu oncogenic protein as a model, a well-defined tumor antigen in breast cancer, we questioned whether patients with advanced stage HER-2/neu overexpressing breast and ovarian cancers (III/IV) had evidence of pre-existent immunity to HER-2/neu. Forty-five patients with stage III or IV HER-2/neu overexpressing breast or ovarian cancer were evaluated for HER-2/neu specific T cell and antibody immunity. Patients enrolled had not received immunosuppressive chemotherapy for at least 30 days (median 5 months, range 1-75 months). All patients were documented to be immune competent prior to entry by DTH testing using a skin test anergy battery. Five of 45 patients (11%) were found to have a significant HER-2/neu specific T cell response as defined by a stimulation index > or = 2.0 (range 2.0-7.9). None of eight patients who were HLA-A2 had a detectable IFNgamma secreting T-cell precursor frequency to a well-defined HER-2/neu HLA-A2 T cell epitope, p369-377. Three of 45 patients (7%) had detectable HER-2/neu specific IgG antibodies, range 1.2-8.9 microg/ml. These findings suggest that patients with advanced stage HER-2/neu overexpressing breast and ovarian cancer can mount a T cell and/or antibody immune response to their tumor. However, in the case of the HER-2/neu antigen, the pre-existent tumor specific immune response is found only in a minority of patients.
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PMID:Pre-existent immunity to the HER-2/neu oncogenic protein in patients with HER-2/neu overexpressing breast and ovarian cancer. 1107 89

To evaluate the ability of serum c-erbB-2 protein to (1) indicate occult and manifest metastases and (2) reflect response to first-line therapy, serial serum c-erbB-2 measurements were performed in a retrospective series of 52 primary breast cancer patients who had developed metastatic disease during follow-up. The results were compared with CA 15-3. Preoperatively, 31% (16/52) of the primary breast cancer patients had elevated c-erbB-2 concentrations. The CA 15-3 positivity rate was 13% (7/52). After surgery, 10 of the 52 patients showed either stable but highly elevated or rising c-erbB-2 serum levels indicating serum c-erbB-2 producing minimal residual disease. Increasing CA 15-3 concentrations were seen in only three patients. Elevated serum c-erbB-2 levels predicted manifest metastases in 27 and 50% of the patients at 6 and 3 months, respectively, prior to clinical diagnosis. CA 15-3 was less sensitive. Only 16 and 32% of the patients had increased CA 15-3 serum concentrations at 6 and 3 months, respectively, prior to clinical detection. The positivity rates of c-erbB-2 and CA 15-3 were similar when metastases were clinically diagnosed. Elevated c-erbB-2 concentrations were found in 62% (32/52). The sensitivity of CA 15-3 was 56% (29/52). The association between serum profiles and response to first-line therapy was evaluated in detail for 45 patients. Serial c-erbB-2 and CA 15-3 measurements reflected disease course in 24 and 27 patients, respectively. The serum profiles of c-erbB-2 and CA 15-3 were similar in 17 patients. In summary, our results suggest that serial determinations of serum c-erbB-2 are useful to monitor breast cancer patients.
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PMID:Clinical utility of serial serum c-erbB-2 determinations in the follow-up of breast cancer patients. 1224 12

The c-erbB-2 proto-oncogene encodes a 185 kDa transmembrane Type 1 tyrosine kinase receptor whose amplification and/or overexpression has been linked with poor prognosis in a variety of cancers. The oncoprotein has been suggested to play a key role in tumour cell invasion, motility and metastasis, and in responsiveness to therapeutic agents. Over-expression of c-erbB-2 therefore identifies an important subset of patients with a high probability of relapse, but low probability of response to certain conventional therapies. The cell surface location of the oncoprotein, its stability of expression and low levels in normal adult tissues render it an attractive target for immunotherapeutic intervention. Although a 'self' antigen, there is evidence that c-erbB-2 p185 can induce both humoral and cell-mediated immune responses in cancer patients. Approaches to exploit p185 as an immunotherapeutic target include vaccination with peptides, plasmid DNA or vectors (viruses/bacteria) carrying the gene; with cytokines, co-stimulatory factors and superantigens being evaluated as adjuvants. Many monoclonal antibody (mAb)-based strategies are also in clinical development. Monoclonal antibodies can serve multiple functions; direct inhibition of c-erbB-2 activity, recruitment of host effector mechanisms and direct or indirect delivery of toxic payloads. Clinical trials in patients with late stage disease have shown that many of these approaches are safe, feasible and relatively non-toxic, and, in some cases, objective responses have been seen. As with all immunotherapy, the greatest benefit is likely to be obtained in patients with minimal residual disease in an adjuvant setting; such studies are awaited with interest.
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PMID:c-erbB-2 as a target for immunotherapy. 1599 36

Treatment of breast cancer in the adjuvant setting has changed rapidly over the last few years. In addition to improvements in chemotherapy, radiation, hormone manipulation, and surgery, immunotherapy has emerged as an effective adjunct for the treatment of breast cancer. Passive immunotherapeutic agents such as trastuzumab have been widely adopted as the standard of care for HER-2/neu overexpressing breast cancer. Vaccine therapy in the metastatic setting has yet to demonstrate clinical significance in a phase III testing. This may be due to the enhanced immunosuppressive effects demonstrated in the tumor microenvironment. Lack of co-stimulatory molecules, activation of the cytotoxic T-lymphocyte antigen-4 (CTLA-4), increased T regulatory cells as well as soluble immunosuppressive factors produced by the tumor contribute to the ineffectiveness of vaccine therapy. Based on these observations, there has been a shift towards treating patients with minimal residual disease and a high risk of relapse. In this adjuvant setting, immune mechanisms of tumor evasion are less formidable, and the use of vaccine therapy in these patients may offer a higher chance of clinical benefit. There are several different vaccine approaches, including the use of cell-based vaccines (autologous, allogeneic, or dendritic cell-based), tumor-associated peptide or protein vaccines, DNA vaccines, heat shock proteins, and recombinant technology using viral or bacterial vectors to enhance immunogenicity of vaccine preparations. This review summarizes principles involving vaccine formulation and antigen selection, followed by a brief synopsis of therapeutic vaccines given in the metastatic setting and possible reasons for their lack of efficacy. The current literature regarding vaccine development for the treatment of breast cancer in the adjuvant setting is also reviewed.
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PMID:Therapeutic breast cancer vaccines: a new strategy for early-stage disease. 1975 18