Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is growing evidence that in multiple myeloma (MM) tumor-directed immune responses exist, might influence tumor progress and could be putative targets for immunotherapeutic approaches. Peripheral blood T lymphocytes are capable of suppressing monoclonal immunoglobulin production of autologous myeloma plasma cells in vitro. This activity can be enhanced by stimulation with mitogens, OKT3 monoclonal antibody or interleukin 2 (IL-2), and is obviously mediated by cytolytic T lymphocytes as demonstrated in a cytotoxicity assay using purified MM plasma cells as targets. The lytic activity is significantly higher when the effectors are prestimulated with irradiated autologous MM plasma cells. Based on these results 18 MM patients of advanced stages with tumor progress received 9 x 10(6) IU/m2 recombinant IL-2 (Proleukin) twice daily on days 1 and 2 and 0.9 x 10(6) IU/m2 twice daily for five subsequent days per week s.c. from days 3-56 (q 12 weeks). During therapy the number of eosinophils increased 15-fold, CD4+ T lymphocytes were activated as demonstrated by CD25 antigen expression and CD56+ natural killer (NK) cells expanded in the peripheral blood. NK cell activity and lymphokine-activated killer cell activity were significantly enhanced. IL-2 therapy induced endogenous IL-2 production and elevated soluble IL-2 receptor serum concentrations. Tumor response was observed in 6/17 evaluable patients. These data indicate that low-dose IL-2 treatment can stimulate immune enhancement in MM patients despite their characteristic tumor-induced immunodeficiency, and has proven to have limited efficacy in advanced MM patients.
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PMID:Tumor-directed cytotoxicity in multiple myeloma--the basis for an experimental treatment approach with interleukin 2. 852 May 15

The purpose of these studies was to develop immunogenic peptides derived from the CD19 and CD20 self-antigens for the induction of antigen-specific CTLs against B-cell malignancies. A total of seven peptides were designed and examined for their HLA-A2.1 affinity and immunogenicity. Of these peptides, we identified two highly immunogenic HLA-A2.1-specific peptides, CD19(150-158) (KLMSPKLYV) and CD20(188-196) (SLFLGILSV), which were capable of inducing peptide-specific CTLs. The CTLs displayed HLA-A2.1-restricted and antigen-specific cytotoxicity against Burkitt's lymphoma, chronic B cell leukemia, and multiple myeloma cell lines. The CD19 or CD20 peptide-specific CTL cytotoxicity was confirmed using HLA-A2.1(+) T2 cells presenting the appropriate peptide. No cytotoxic activity was observed against T2 cells presenting the irrelevant MAGE-3 peptide or T2 cells alone. In addition, the CTLs displayed a significant (P < 0.05) increase in cell proliferation and IFN-gamma secretion (>830 ng/mL) following restimulation with HLA-A2.1(+)/CD19(+)/CD20(+) tumor cells. The CTLs also displayed a distinct phenotype consisting of a high percentage of CD69(+)/CD45RO(+) and a low percentage of CD45RA(+)/CCR7(+) CD4(+) or CD8(+) T cells characteristic of effector memory cell population. Cyclic guanosine 3',5'-monophosphate culture conditions using serum-free AIM-V medium containing human AB serum, recombinant human interleukin 2 (Proleukin) and CD3/CD28 Dynabeads were developed resulting in a 35-fold expansion of CD20 peptide-specific CTLs. The expanded CD20-CTLs retained their cytotoxic activity (28-49%) against the Burkitt's lymphoma cell line. In conclusion, we report here on the identification of novel immunogenic CD19(150-158) (KLMSPKLYV) and CD20(188-196) (SLFLGILSV) peptides that have immunotherapeutic potentials as peptide vaccines or targeted T-cell therapies for treating B-cell malignancies.
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PMID:Identification of CD19 and CD20 peptides for induction of antigen-specific CTLs against B-cell malignancies. 1574 68