Biomedical subjects

Anna Maria Di Giacomo

Publications and source records attributed to Anna Maria Di Giacomo.

5 recordsLinked to original sources

PubMed2006

Phenotypic and functional changes of human melanoma xenografts induced by DNA hypomethylation: immunotherapeutic implications.

Emerging in vitro evidence points to an immunomodulatory activity of DNA hypomethylating drugs in human malignancies. We investigated the potential of 5-aza-2'-deoxycytidine (5-AZA-CdR) to modulate the expression of cancer testis antigens (CTA) and of HLA class I antigens by melanoma xenografts, and the resulting modifications in immunogenicity of neoplastic cells. Three primary cultures of melanoma cells, selected for immune phenotype and growth rate, were grafted into BALB/c nu/nu mice that were injected intraperitoneally with different dose- and time-schedules of 5-AZA-CdR. Molecular analyses demonstrated a de novo long-lasting expression of the CTA MAGE-1, -2, -3, -4, -10, GAGE 1-6, NY-ESO-1, and the upregulation of MAGE-1, MAGE-3, and NY-ESO-1 levels in melanoma xenografts from 5-AZA-CdR-treated mice. Serological and biochemical analyses identified a de novo expression of NY-ESO-1 protein and a concomitant and persistent upregulation of HLA class I antigens and of HLA-A1 and -A2 alleles. Immunization of BALB/c mice with 5-AZA-CdR-treated melanoma cells generated high titer circulating anti-NY-ESO-1 antibodies. Altogether, the data obtained identify an immunomodulatory activity of 5-AZA-CdR in vivo and strongly suggest for its clinical use to design novel strategies of CTA-based chemo-immunotherapy for melanoma patients.

Animals↗

PubMed2005

Epigenetic modulation of solid tumors as a novel approach for cancer immunotherapy.

Emerging evidence demonstrates that epigenetic events associated with tumor development and progression may impair immunogenicity and immune recognition of cancer cells, possibly favoring their escape also from vaccination-induced antitumor immune responses. In fact, DNA hypermethylation and/or histone deacetylation plays a critical role in the downregulation and/or silencing of several genes involved in the recognition of neoplastic cells by the immune system, including human leukocyte antigens (HLAs), tumor-associated antigens, and accessory/costimulatory molecules. However, as opposed to genetic alterations, epigenetic events can be successfully handled through pharmacologic agents that induce DNA hypomethylation or inhibit histone deacetylation, resulting in a functionally "more efficient" immune profile of cancer cells. In light of the encouraging immunomodulatory results obtained with these "epigenetic drugs," they certainly will be used for the development of combined chemo-immunotherapeutic strategies for the treatment of patients with solid malignancies of different histology.

Animals↗

PubMed2005

Epigenetic immunomodulation of hematopoietic malignancies.

Significant progress has been made in the clinical management of hematologic malignancies; nevertheless, a proportion of patients still remains unresponsive to available therapeutic options. Furthermore, patients who respond to specific therapeutic regimens may still require additional treatment to eradicate minimal residual disease. In this scenario, novel immunotherapeutic strategies may significantly impact on the clinical course of hematopoietic tumors in different clinical stages of disease. Among immunotherapeutic approaches under development, promising clinical results are being obtained with vaccination of patients with solid malignancies against cancer testis antigens (CTA), which belong to a growing family of methylation-regulated tumor-associated antigens (TAA) shared among human malignancies of different histologies. Based on these notions, the emerging preclinical and clinical evidence suggest that an immunomodulatory role for epigenetic drugs is highly relevant; in fact, by interfering with DNA methylation, these compounds induce or upregulate the constitutive expression of CTA on actively proliferating neoplastic cells. This novel activity of epigenetic drugs combines with their well-known cytotoxic, pro-apoptotic and differentiating activities in hematopoietic tumors that are extensively described in other chapters of this issue. This review will focus on the expression of CTA in hematopoietic malignancies, on their epigenetic regulation, and on the foreseeable immunotherapeutic implications of DNA hypometylating drugs to design new CTA-based chemo-immunotherapeutic approaches in patients with hematopoietic tumors.

Antigens, Neoplasm↗

PubMed2004

Optimizing complement-activating antibody-based cancer immunotherapy: a feasible strategy?

Passive immunotherapy with monoclonal antibodies (mAb) targeted to specific tumor-associated antigens is amongst the most rapidly expanding approaches to biological therapy of cancer. However, until now a limited number of therapeutic mAb has demonstrated clinical efficacy in selected neoplasia. Results emerging from basic research point to a deeper characterization of specific biological features of neoplastic cells as crucial to optimize the clinical potential of therapeutic mAb, and to identify cancer patients who represent the best candidates to antibody-based immunotherapy. Focus on the tissue distribution and on the functional role of membrane complement-regulatory proteins such as Protectin (CD59), which under physiologic conditions protects tissues from Complement (C)-damage, might help to optimize the efficacy of immunotherapeutic strategies based on C-activating mAb.

Editorial↗

PubMedDate not supplied

Residual telomerase activity: a marker of cell survival after exposure to gamma radiation in vitro.

BACKGROUND: Residual telomerase activity (TA) could be used as a marker of malignant or normal cell survival after exposure to cytotoxic agents. Therefore TA after treatment with ionizing radiation was used in a radiosensitivity assay. MATERIALS AND METHODS: Radiosensitive MOLT-4 and relatively radioresistant Jurkat leukemia cells or normal peripheral blood mononuclear cells (MNC) were irradiated with 5-160 Gy. Cell count, MTT assay and telomerase activity were evaluated on day 3 and clonogenic assay on day 10. RESULTS: In Jurkat cells, irradiation inhibited tumor growth and total TA per culture (TA/culture), but up-regulated TA per viable cell (TA/cell). TA/culture and TA/cell were profoundly depressed by irradiation of MOLT-4 or phytohemagglutinin-activated MNC. CONCLUSION: Susceptibility of normal or neoplastic cells to high-dose radiation can be monitored by evaluating residual TA/culture. In some cases, however, difficulties in the interpretation of the results could stem from radiation-induced increase of TA/cell, as observed for the Jurkat cell line.

Apoptosis↗