Modulation of the antigenic phenotype of human breast carcinoma cells by modifiers of protein kinase C activity and recombinant human interferons

Leon, Jorge A.; Gutiérrez, Michelle; Jiang, Hai; Estabrook, Alison; Waxman, Samuel; Fisher, Paul B.

doi:10.1007/bf01741144

Cited by 9 publications

(5 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6). Some earlier evidence also has suggested that the antigenic phenotypes of breast carcinoma and astrocytoma cells can be modified by IFN-␤ treatments (51,52), and dramatic antitumor activity has been noted in a patient with ovarian cancer treated with immunotherapy and adenovirally expressed IFN-␤ (53). The diverse nature of such cellular IFN-␤ responses suggested that the up-regulatory process was either dependent on normal ubiquitous factors, or factors aberrantly expressed in each of these tumor cell lines.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of Human Melanoma Antigen Expression by IFN-β

Dunn

Haggerty

Kono

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

Although many immunotherapeutic investigations have focused on improving the effector limb of the antitumor response, few studies have addressed preventing the loss of tumor-associated Ag (TAA) expression, associated with immune escape by tumors. We found that TAA loss from human melanomas usually results from reversible gene down-regulation, rather than gene deletion or mutation. Previously, we showed that inhibitors of MAPK-signaling pathways up-regulate TAA expression in melanoma cell lines. We have now identified IFN-β as an additional stimulus to TAA expression, including Melan-A/MART-1, gp100, and MAGE-A1. IFN-β (but neither IFN-α nor IFN-γ) augmented both protein and mRNA expression of melanocytic TAA in 15 melanoma lines (irrespective of initial Ag-expression levels). Treatment of low Ag melanoma lines with IFN-β increased expression of melanocyte-lineage Ags, inducing susceptibility to lysis by specific CTLs. Treatment with IFN-β also enhances expression of class I HLA molecules, thereby inducing both nominal TAA and the presenting HLA molecule. Data from fluorescent cellular reporter systems demonstrated that IFN-β triggers promoter activation, resulting in augmentation of Ag expression. In addition to enhancing TAA expression in melanomas, IFN-β also stimulated expression of the melanocytic Ag gp100 in cells of other neural crest-derived tumor lines (gliomas) and certain unrelated tumors. Because IFN-β is already approved for human clinical use in other contexts, it may prove useful as a cotreatment for augmenting tumor Ag expression during immunotherapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Enhancement of Human Melanoma Antigen Expression by IFN-β

Dunn

Haggerty

Kono

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Prompted by such findings and with the intent to identify simplified PE analogs using a function-oriented synthesis (FOS) strategy [19][20][21] , we reported in 1986 a computerbased analysis of the pharmacophore of PEs and related PKC modulating ligands, which led to the first designed PKC modulator-3-(N-acetylamino)-5-(N-decyl-N-methylamino)-benzyl alcohol (ADMB) 22 . In 1992, Leon et al 23 showed that ADMB, like the PEs, enhanced tumor associated antigen (BCA-225) expression in breast carcinoma cells but, unlike PEs, it did not induce shedding of the antigen, highlighting the potential for natural product-inspired designed analogs to exhibit divergent and superior biological activity. Significantly, the immunomodulatory properties of the PEs are not unique to this structural class of PKC modulators.…”

mentioning

confidence: 99%

Synthesis and evaluation of designed PKC modulators for enhanced cancer immunotherapy

Hardman

Shimizu

et al. 2020

Nat Commun

View full text Add to dashboard Cite

Bryostatin 1 is a marine natural product under investigation for HIV/AIDS eradication, the treatment of neurological disorders, and enhanced CAR T/NK cell immunotherapy. Despite its promising activity, bryostatin 1 is neither evolved nor optimized for the treatment of human disease. Here we report the design, synthesis, and biological evaluation of several close-in analogs of bryostatin 1. Using a function-oriented synthesis approach, we synthesize a series of bryostatin analogs designed to maintain affinity for bryostatin's target protein kinase C (PKC) while enabling exploration of their divergent biological functions. Our latestage diversification strategy provides efficient access to a library of bryostatin analogs, which per our design retain affinity for PKC but exhibit variable PKC translocation kinetics. We further demonstrate that select analogs potently increase cell surface expression of CD22, a promising CAR T cell target for the treatment of leukemias, highlighting the clinical potential of bryostatin analogs for enhancing targeted immunotherapies.

show abstract

“…An LS174T and SW480 (colorectal), HeLa (cervical), DU-145 (prostate), and HONE-1 (nasopharyngeal) (9,(22)(23)(24)(25), were grown in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum (DMEM-10) at 37°C in a 5% C02/95% airhumidified incubator. Additional human cell types including HBL-100 (normal mammary epithelial), HO-1 and C8161 (melanoma), GBM-18 and T98G (glioblastoma multiforme), and Saos-2 (human osteosarcoma) were maintained under similar conditions.…”

mentioning

confidence: 99%

The melanoma differentiation associated gene mda-7 suppresses cancer cell growth.

Jiang

Su²,

Lin³

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

270

259

View full text Add to dashboard Cite

Cancer is a disease characterized by defects in growth control, and tumor cells often display abnormal patterns of cellular differentiation. The combination of recombinant human fibroblast interferon and the antileukemic agent mezerein corrects these abnormalities in cultured human melanoma cells resulting in irreversible growth arrest and terminal differentiation. Subtraction hybridization identifies a melanoma differentiation associated gene (mda-7) with elevated expression in growth arrested and terminally differentiated human melanoma cells. Colony formation decreases when mda-7 is transfected into human tumor cells of diverse origin and with multiple genetic defects. In contrast, the effects of mda-7 on growth and colony formation in transient transfection assays with normal cells, including human mammary epithelial, human skin fibroblast, and rat embryo fibroblast, is quantitatively less than that found with cancer cells. Tumor cells expressing elevated mda-7 display suppression in monolayer growth and anchorage independence. Infection with a recombinant type 5 adenovirus expressing antisense mda-7 eliminates mda-7 suppression of the in vitro growth and transformed phenotype. The ability of mda-7 to suppress growth in cancer cells not expressing or containing defects in both the retinoblastoma (RB) and p53 genes indicates a lack of involvement of these critical tumor suppressor elements in mediating mda-7-induced growth inhibition. The lack of protein homology of mda-7 with previously described growth suppressing genes and the differential effect of this gene on normal versus cancer cells suggests that mda-7 may represent a new class of cancer growth suppressing genes with antitumor activity.Cancer is a complex multifactor and multistep process involving the coordinated expression and suppression of genes functioning as positive and negative regulators of oncogenesis (1-5). Direct cloning strategies, based on transfer of a dominant transforming or tumorigenic phenotype, have identified positive acting oncogenes (6-9). In contrast, the detection and cloning of genes that suppress the cancer phenotype have proven more difficult and elusive (10-15). A direct approach for isolating genes directly involved in regulating growth and differentiation involves subtraction hybridization between cDNA libraries constructed from actively growing cancer cells and cDNA libraries from cancer cells induced to lose proliferative capacity irreversibly and terminally differentiate (13,14). This experimental strategy has been applied to human melanoma cells, induced to terminally differentiate by treatment with recombinant human interferon 3 (IFN-4) and mezerein (MEZ), resulting in the cloning of novel melanoma differentiation-associated (mda) genes not previously described in DNA data bases (13,14). A direct role for specific mda genes in mediating growth and cell cycle control is apparent by the identification and cloning of mda-6 (13-16), which is identical to the ubiquitous inhibitor of cyclindependent kinases p21 (...

show abstract

Modulation of the antigenic phenotype of human breast carcinoma cells by modifiers of protein kinase C activity and recombinant human interferons

Cited by 9 publications

References 46 publications

Enhancement of Human Melanoma Antigen Expression by IFN-β

Enhancement of Human Melanoma Antigen Expression by IFN-β

Synthesis and evaluation of designed PKC modulators for enhanced cancer immunotherapy

The melanoma differentiation associated gene mda-7 suppresses cancer cell growth.

Contact Info

Product

Resources

About