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

Monoclonal antibodies (MA) were obtained by fusion of a myeloma line from mice with spleen cells of mice previously immunized by live human cells of uveal melanoma of an epithelioid type (UMEL-H). From the cell fusion hybridomas were obtained which produced antibodies against immunized uveal melanoma cells. The binding capacity of MA was assessed by the sandwich radio-immuno (RIA) test using indirect immunofluorescence. Extensive specific tests revealed that MA are strongly bound to uveal melanoma, the cells of which were used to immunize the mice, but also fresh allogenic uveal melanoma cells UMEL-K which were also of the epithelioid type. A smaller binding activity was observed with the cell line of the uveal melanoma VUP-1 which was started 16 years ago and is formed by 92% by epithelioid cells. A smaller binding activity of MA was observed with the line of skin melanoma cells (HMB-2, B-HM8). The bond of MA with carcinomatous cells, fibroblasts, uveal and retinal cells from eyes of healthy humans was negative. The preliminary investigations indicate an antigenic homogeneity of tumour antigens of melanoma cells of the same histological type and the antigenic variability of uveal and skin melanomas.
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PMID:[Detection of surface antigens in uveal melanoma using monoclonal antibodies]. 274 34

Mouse Sp2/10 myeloma cells were fused with spleen cells from mice that had been immunized with freshly obtained primary human uveal melanoma cells. Hybrids that produced antibodies binding to the uveal melanoma cells, but not to fibroblasts, uveal or retinal cells of healthy donors, were cloned. Extensive specificity tests showed that the antibodies produced by the ten clones bound strongly to fresh or short-time cultures of primary human uveal melanoma tumor cells (UMEL-H, UMEL-K). Weaker binding occurred with a human uveal melanoma cell line (VUP-1), and with human skin melanoma cell lines (HMB-2, B-HM8), respectively. Binding assays with carcinoma cells, fibroblasts, uveal and retinal cells were negative. An intensive screening of this type is now under way.
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PMID:A preliminary report on monoclonal antibodies against human uveal melanoma. 343 9

We have shown that administration of a novel anti-CD54 monoclonal antibody (UV3) results in long-term survival of SCID mice bearing human myeloma xenografts. Previous studies have demonstrated a link between the expression of CD54 and the progression of uveal melanoma. Our study assessed the expression of CD54 on 7 human uveal melanoma cell lines and 3 cell lines established from uveal melanoma metastases. In vivo studies examined the efficacy of systemic and local administration of UV3 antibody on the progression of uveal melanoma cells transplanted either heterotopically or orthotopically into SCID mice. Five of the 7 primary uveal melanoma cell lines and all 3 of the metastases cell lines expressed CD54. Intraperitoneal injection of either IgG or F(ab')2 fragments of UV3 significantly inhibited the growth of subcutaneous and intraocular melanomas. Subconjunctival injection of either IgG or F(ab')2 fragments of UV3 produced a significant reduction in the growth of intraocular melanomas, even if the antibody was administered after the appearance of intraocular tumors. The results indicate that both primary and metastatic human uveal melanoma cells express CD54. The marked inhibition of intraocular and subcutaneous uveal melanoma progression suggests that UV3 antibody is a promising therapeutic agent for further evaluation in patients with uveal melanoma. This is especially noteworthy, as no existing therapeutic modality prevents metastasis of uveal melanoma or prolongs the survival of patients with uveal melanoma.
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PMID:Effect of an anti-CD54 (ICAM-1) monoclonal antibody (UV3) on the growth of human uveal melanoma cells transplanted heterotopically and orthotopically in SCID mice. 1615 88

The success of cancer immunotherapy is limited by resistance to immune checkpoint blockade. We therefore conducted a genetic screen to identify genes that mediated resistance against CTLs in anti-PD-L1 treatment-refractory human tumors. Using PD-L1-positive multiple myeloma cells cocultured with tumor-reactive bone marrow-infiltrating CTL as a model, we identified calcium/calmodulin-dependent protein kinase 1D (CAMK1D) as a key modulator of tumor-intrinsic immune resistance. CAMK1D was coexpressed with PD-L1 in anti-PD-L1/PD-1 treatment-refractory cancer types and correlated with poor prognosis in these tumors. CAMK1D was activated by CTL through Fas-receptor stimulation, which led to CAMK1D binding to and phosphorylating caspase-3, -6, and -7, inhibiting their activation and function. Consistently, CAMK1D mediated immune resistance of murine colorectal cancer cells in vivo The pharmacologic inhibition of CAMK1D, on the other hand, restored the sensitivity toward Fas-ligand treatment in multiple myeloma and uveal melanoma cells in vitro Thus, rapid inhibition of the terminal apoptotic cascade by CAMK1D expressed in anti-PD-L1-refractory tumors via T-cell recognition may have contributed to tumor immune resistance.
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PMID:CAMK1D Triggers Immune Resistance of Human Tumor Cells Refractory to Anti-PD-L1 Treatment. 3266 63