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Biomedical subjects

K Rinn

Publications and source records attributed to K Rinn.

8 recordsLinked to original sources
PubMed2000

Pre-existent immunity to the HER-2/neu oncogenic protein in patients with HER-2/neu overexpressing breast and ovarian cancer.

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.

Adenocarcinoma↗
PubMed2000

Delayed-type hypersensitivity response is a predictor of peripheral blood T-cell immunity after HER-2/neu peptide immunization.

Many groups that immunize cancer patients with cancer vaccines use the generation of a delayed-type hypersensitivity (DTH) response as the primary measure of the ability to immunize a patient to a tumor cell or specific tumor antigen. This study examines whether the development of a tumor antigen-specific DTH response, measured after vaccination with peptide-based vaccines, correlates to in vitro assessment of peripheral blood antigen-specific T-cell responses. The HER-2/neu protein was used as a model tumor antigen. Thirty-two patients who completed a course of immunization with HER-2/neu peptide-based vaccines were analyzed. HER-2/neu peptide-specific DTH responses (n = 93) and peripheral blood T-cell responses (n = 93) were measured 30 days after the final immunization. Size of DTH induration was correlated with HER-2/neu-specific T-cell proliferative responses assessed from peripheral blood lymphocytes isolated concurrently with peptide skin test placement. HER-2/neu peptide-specific DTH responses > or =10 mm2 correlated significantly to a measurable peptide-specific peripheral blood T-cell response defined as stimulation index >2.0 (P = 0.0006). However, antigen-specific DTH responses with magnitudes between 5 and 9 mm2 were not significantly associated with the development of systemic immunity. DTH responses between 5 and 9 mm2 carried an odds ratio of 1.3 (P = 0.61) in predicting a measurable systemic tumor antigen response. The findings presented here demonstrate that tumor antigen-specific DTH responses > or =10 mm2 correlate with measurable in vitro antigen-specific lymphocytic proliferation and are, in this model system, a reflection of systemic immunization.

Breast Neoplasms↗
PubMed1999

Immunotherapeutic approaches for the treatment of breast cancer.

The application of immunotherapeutic principles to the treatment and prevention of breast cancer is a relatively new undertaking. Although cytokine infusions, cancer vaccines, and T cell therapy have been extensively studied in solid tumors such as melanoma and renal cell carcinoma, the therapeutic efficacy of these approaches is not well explored in breast cancer. The recent definition of tumor-specific immunity in breast cancer patients and the identification of several breast cancer antigens has generated enthusiasm for the application of immune-based therapies to the treatment of breast malignancies. In general, immunotherapies can be considered either non-specific, such as a general immunomodulator (e.g., a cytokine), or tumor-specific (e.g., a vaccine that targets breast cancer tumor antigens). This review describes three major immunotherapeutic strategies that have the potential to enhance or generate an anti-breast cancer T cell immune response: (i) cytokine therapy; (ii) cancer vaccines; and (iii) T cell therapy, and explores how each strategy has been applied to the treatment of breast cancer.

Animals↗