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5. Study of Attitudes of the Elderly Toward Aging & the Aged.

Author

Signori, E. I. and Kozak, J.

Abstract

This study provides a closer perspective and appreciation of what elderly people think and feel about aging and the aged. Contained herein is a summary of the recorded written responses of 200 consecutive statements received from male and female persons 65 years old and over, in response to several broad questions regarding aging and the aged. The summary statements attempt to capture the diversity of meaning found in the recorded statements about a number of issues which are of interest to the elderly surveyed. In the issues discussed, no claim is made that the trends shown are generalizable to the total population of the elderly in British Colombia. However, that the issues may be of concern to a large number of the elderly is not contraindicated by these data. The additional, though as yet unanalyzed, data at hand from approximately 400 other respondents eventually should prove useful in confirming or disconfirming the consistency of present trends. Currently an attempt is being made to relate the experimental findings reported herein to findings obtained by studies using questionnaire and/or structured interview procedure. (Author)

Published
1976

6. Expression and heterodimer-binding activity of Ku70 and Ku80 in human non-melanoma skin cancer

Author

Parrella, P., Mazzarelli, P., Signori, E., Perrone, G., Marangi, G.F., Rabitti, C., Delfino, M., Prencipe, M., Gallo, A.P., Rinaldi, M., Fabbrocini, G., Delfino, S., Persichetti, P., and Fazio, V.M.

Subjects
Gene expression -- Research, Ultraviolet radiation -- Health aspects, Ultraviolet radiation -- Research, Skin cancer -- Genetic aspects, Skin cancer -- Research, Health
Published
2006

18. Electroporation in DNA vaccination protocols against cancer

Author

Chiarella P, Fazio VM, and Signori E.

Subjects
DNA vaccine, electroporation, tumour antigen, cancer, immune response
Abstract

Since conventional therapeutic approaches in cancer are highly invasive they hardly prolong patient survival for more than few months. Having the ability to stimulate both cellular and humoural immune responses, immunisation with naked plasmid DNA encoding tumour-associated antigens or tumour-specific antigens has recently reported a plethora of advantages, and the improvement of vaccine efficacy has emerged as a goal in the development of DNA vaccination as anti-tumour therapy. Nevertheless, because of their poor immunogenicity when administered as unformulated intramuscular injections, plasmid DNA vaccines need to be improved. Recent data suggest that the DNA vaccine efficacy may significantly be increased by electroporation. This review highlights the recent literature that supports electroporation as an effective strategy to improve DNA-based vaccination protocols, investigating the most relevant studies, recently developed for the applications of DNA vaccine electrotransfer against tumours in pre-clinical and clinical studies.

Published
2013

20. “DNA vaccines for B-cell lymphomas: towards personalised medicine and tailored drugs”

Author

Iurescia S., Fioretti D., Pierimarchi P., Signori E., Zonfrillo M., Fazio V.M., and Rinaldi M.

Abstract

DNA vaccine platform has produced exciting results in a wide array of applications, from prophylactic vaccine strategies to poten- tial therapeutics targeting cancers and infectious disease (Fioretti et al., 2010; Rinaldi et al., 2009; Rinaldi et al., 2006; Fazio et al., 2004). Many tumor antigens are excellent targets for active immunotherapy and can be presented by DNA vaccines in a molecular form suitable to engage both humoral and cellular immune responses. Our group is involved in the development of DNA vaccination strategies as active immunotherapy for the treatment of B-cell lym- phomas. The idiotype region in the immunoglobulin expressed on the surface of B-cell lymphomas is a tumour-specific as well a patient-specific antigen and an ideal target for personalised immunotherapy. We focused on the idiotypic determinants lying within the CDR3 hypervariable regions and demonstrated that immunisation with CDR3-based DNA vaccines elicited anti- idiotypic humoral response able to recognize native antigens on tumour cells (Rinaldi et al., 2001). In a highly aggressive preclinical murine B-cell lymphoma model, we evaluated the antitumour response recruited by CDR3- based DNA vaccines. We showed that a combination of CDR3-based DNA vaccines with electroporation in a homologous prime-boost approach was protective against a lethal tumour challenge (Rinaldi et al., 2008; Iurescia et al., 2010). Since a goal of our studies is the development of tai- lored immunisation strategies against previously established tumours, efforts are ongoing to optimize the DNA vaccine tech- nology platform. Strategies to improve antigen expression and immunogenicity involve epitope prediction, MHC I presentation enhancement, inclusion of pathogen-derived sequences aimed to stimulate CD4+ T cell help and immunomodulating cytokines. Preliminary results encourage the use of therapeutic protocols based on DNA vaccines as tailored drugs for the treatment of lymphoma. Optimal integration of active immunization approaches into standard therapies suggests DNA vaccination as an effective per- sonalized medicine to eradicate minimal residual diseases during clinical remission following standard chemotherapy in lymphoma patients.

Published
2010

21. Recent advances in epitope design for immunotherapy of cancer

Author

Chiarella P., Massi E., De Robertis M., Fazio V.M., and Signori E.

Subjects
clinical trials, in silico' prediction, epitope enhancement, immunotherapy, Cancer
Abstract

Eradication of cancer cells is imperative for a successful treatment of tumours. In addition to the existent chemotherapy or radiation therapy, other novel immunotherapeutic strategies to fight tumours are currently under investigation. One of these is cancer vaccination, an approach aimed at inducing effective immune responses in the host against defined tumour antigens. Among several classes of cancer vaccines, the subunit vaccines based on the single and multi epitope-approach are worthy of note as they offer an exquisite specificity in targeting only tumour cells. In this review we will focus on the significant advances made in the development and use of epitope-based cancer vaccines, reporting a selection of important and recent patents on tumour antigen discovery and epitope design for immunotherapy of cancer.

Published
2009

23. An overview of Apoe for application in gene therapy

Author

Rinaldi M., Iurescia S., Fioretti D., Massi E., and Signori E

Subjects
lipids (amino acids, peptides, and proteins)
Abstract

Atherosclerosis, one of the most prevalent and severe age-related diseases, is the leading cause of death in industrialized countries and it is becoming an increasingly worldwide risk to health. As the size of elderly population grows, the incidence of atherosclerosis will increase, necessitating the exploration of radical, but potentially powerful, therapeutic strategies. One important goal is the availability of therapeutic molecules effective against the atherosclerotic plaque progression and able to stabilize advanced lesions. This generally requires robust measures to improve plasma lipoprotein profiles. Pharmaceutical agents currently available do not support significant changes in plasma lipoprotein levels. So that, strong new agents and therapies are needed in order to treat hyperlipidemia and atherosclerosis. Apolipoprotein E (ApoE), a key regulator in cholesterol-rich lipoprotein metabolism, is considered a strong candidate for treating hypercholesterolemia and cardiovascular disease. ApoE gene therapy could be proposed as a new valid approach for the correction of hyperlipidemic conditions and atherosclerosis by using viral and non-viral vectors. In this review we discuss the major developments in both viral and non-viral gene transfer systems aimed at achieving efficient protocols for treating hypercholesterolemia and atherosclerosis by using ApoE as therapeutic gene. Key scientific advances on the ability of ApoE gene transfer to markedly improve outcome after cerebral ischemia, suggesting a potential strategy in human stroke therapy, are also described in this review. The characterization of ApoE and its many functions has provided insight into the ultimate potential of this protein as a possible therapeutic agent for the treatment of several diseases. Possible therapeutic strategies that encompass the use of ApoE in gene therapy for Alzheimer's disease and other central nervous system (CNS) diseases will be also discussed.

Published
2009

24. ICON2: randomised trial of single-agent carboplatin against three-drug combination of CAP (cyclophosphamide, doxorubicin, and cisplatin) in women with ovarian cancer

Author

Parmar MKB, Torri V, Bonaventura A, Bonazzi C, Colombo N, Delaloye JF, Marsoni S, Mangioni C, Sandercock J, Sessa C, Williams C, Tinazzi A, Flann M, Geiser K, Scorpiglione N, Stewart JF, Chaves J, Palmeiro E, Curtain A, McCormack T, Gennatas C, Marras F, Oppo TG, Balestrino M, Malzoni C, Malzoni M, Belli M, Geminiani ML, Crestani G, Monaco A, Vavala V, Piatto E, Barattini G, Fornara PG, Chetri MC, Santeufemia G, Artioli F, Carone D, Fanizza G, Trentadue R, Priolo D, Scollo P, Nigro SC, Petrina M, Mastrantonio P, Spanna GD, Zagni R, Belloni C, Colleoni R, Redaelli L, Cavagnini A, Di Costanzo G, Perroni D, Arienti S, Orfanotti G, Cantoni FM, Secli R, Bianchi A, Martinello R, Mollica G, Maizzi D, Picchiarelli ME, Fiorini G, Borsani M, Colombo E, Garsia S, Melgrati L, Paggi G, Brunenghi GM, Casini M, Isa L, Algeri R, Prozio G, Belfiore G, Angelini F, D'Aprile M, Moreschi M, Mauri ML, Natale N, Senzani FM, Pavanato G, Poggi G, Garuti G, Luerti M, Cruciani G, Pagano F, Baccolo M, Poddi ER, Bocciolone L, Sabelli MA, Maggi R, Restelli C, D'Antona A, Locatelli MC, Pessi A, Raina A, Chiari S, Gabriele A, Pittelli MR, Iacobelli P, Dogliotti L, Gorzegno G, Musso P, Vegna G, Coco G, Alletti DG, Picciotto F, Lucchese V, Epis A, di Palumbo VS, Drudi G, Ravaioli A, Zampella D, Morandi MG, Gorga G, Zucchelli C, Cariello S, Galletto L, Sussio M, Massacesi L, Massacesi M, Carli A, Tucci E, Tajani E, Corrado G, Bumma S, Durando A, Massobrio M, Sberveglieri M, Biasio M, Guercio E, Jura R, Danese S, Wierdis T, Farnelli C, Tarantino G, Grassi R, Repetti F, Rocchi B, Grampa M, Ercoli A, Griso C, Signori E, Zanini L, Presti M, Klimek M, Urbanski K, Biswas A, Viegas O, Kochli O, Dreher E, Fey M, Beck G, Ludin J, Bonnefoi H, Krauer F, Bauer J, Delmore G, Furrer C, Lorenz U, Thurlimann B, Bronz L, Sanna P, Wyss D, Goldhirsch A, Gyr T, Leidi L, Pastorelli G, Pagani O, Rey P, Hailer U, Benz J, Kaye SB, Reed NS, Symonds RP, Atkinson RJ, Axford AT, Rustin G, Seckl MJ, Green JA, Scott IV, Guthrie D, Harper PG, Calman F, Dobbs HJ, Weir P, Cassoni A, Lederman JA, Souhami RL, Bozzino J, Adab F, Redman CWE, Scoble JE, Paterson M, Daniel F, Cowley N, Williams CJ, Spooner D, Hong A, McIllmurray M, Hendy-Ibbs P, Hall V, Iveson TJ, Whitehouse JMA, Garry R, Lamont A, Robinson A, Trask CW, Clubb AW, Murrell D, Newman G, Wilkins M, Goldthorp WO, Roberts JK, Radstone DJ, Whipp MJ, Ledermann JA, Pater J, Buyse M, Omura G, Parmar, Mkb, Torri, V, Bonaventura, A, Bonazzi, C, Colombo, N, Delaloye, Jf, Marsoni, S, Mangioni, C, Sandercock, J, Sessa, C, Williams, C, Tinazzi, A, Flann, M, Geiser, K, Scorpiglione, N, Stewart, Jf, Chaves, J, Palmeiro, E, Curtain, A, Mccormack, T, Gennatas, C, Marras, F, Oppo, Tg, Balestrino, M, Malzoni, C, Malzoni, M, Belli, M, Geminiani, Ml, Crestani, G, Monaco, A, Vavala, V, Piatto, E, Barattini, G, Fornara, Pg, Chetri, Mc, Santeufemia, G, Artioli, F, Carone, D, Fanizza, G, Trentadue, R, Priolo, D, Scollo, P, Nigro, Sc, Petrina, M, Mastrantonio, P, Spanna, Gd, Zagni, R, Belloni, C, Colleoni, R, Redaelli, L, Cavagnini, A, Di Costanzo, G, Perroni, D, Arienti, S, Orfanotti, G, Cantoni, Fm, Secli, R, Bianchi, A, Martinello, R, Mollica, G, Maizzi, D, Picchiarelli, Me, Fiorini, G, Borsani, M, Colombo, E, Garsia, S, Melgrati, L, Paggi, G, Brunenghi, Gm, Casini, M, Isa, L, Algeri, R, Prozio, G, Belfiore, G, Angelini, F, D'Aprile, M, Moreschi, M, Mauri, Ml, Natale, N, Senzani, Fm, Pavanato, G, Poggi, G, Garuti, G, Luerti, M, Cruciani, G, Pagano, F, Baccolo, M, Poddi, Er, Bocciolone, L, Sabelli, Ma, Maggi, R, Restelli, C, D'Antona, A, Locatelli, Mc, Pessi, A, Raina, A, Chiari, S, Gabriele, A, Pittelli, Mr, Iacobelli, P, Dogliotti, L, Gorzegno, G, Musso, P, Vegna, G, Coco, G, Alletti, Dg, Picciotto, F, Lucchese, V, Epis, A, di Palumbo, V, Drudi, G, Ravaioli, A, Zampella, D, Morandi, Mg, Gorga, G, Zucchelli, C, Cariello, S, Galletto, L, Sussio, M, Massacesi, L, Massacesi, M, Carli, A, Tucci, E, Tajani, E, Corrado, G, Bumma, S, Durando, A, Massobrio, M, Sberveglieri, M, Biasio, M, Guercio, E, Jura, R, Danese, S, Wierdis, T, Farnelli, C, Tarantino, G, Grassi, R, Repetti, F, Rocchi, B, Grampa, M, Ercoli, A, Griso, C, Signori, E, Zanini, L, Presti, M, Klimek, M, Urbanski, K, Biswas, A, Viegas, O, Kochli, O, Dreher, E, Fey, M, Beck, G, Ludin, J, Bonnefoi, H, Krauer, F, Bauer, J, Delmore, G, Furrer, C, Lorenz, U, Thurlimann, B, Bronz, L, Sanna, P, Wyss, D, Goldhirsch, A, Gyr, T, Leidi, L, Pastorelli, G, Pagani, O, Rey, P, Hailer, U, Benz, J, Kaye, Sb, Reed, N, Symonds, Rp, Atkinson, Rj, Axford, At, Rustin, G, Seckl, Mj, Green, Ja, Scott, Iv, Guthrie, D, Harper, Pg, Calman, F, Dobbs, Hj, Weir, P, Cassoni, A, Lederman, Ja, Souhami, Rl, Bozzino, J, Adab, F, Redman, Cwe, Scoble, Je, Paterson, M, Daniel, F, Cowley, N, Williams, Cj, Spooner, D, Hong, A, Mcillmurray, M, Hendy-Ibbs, P, Hall, V, Iveson, Tj, Whitehouse, Jma, Garry, R, Lamont, A, Robinson, A, Trask, Cw, Clubb, Aw, Murrell, D, Newman, G, Wilkins, M, Goldthorp, Wo, Roberts, Jk, Radstone, Dj, Whipp, Mj, Ledermann, Ja, Pater, J, Buyse, M, and Omura, G

Published
1998

25. ICON2: randomised trial of single-agent carboplatin against three-drug combination of CAP (cyclophosphamide, doxorubicin, and cisplatin) in women with ovarian cancer. ICON Collaborators. International Collaborative Ovarian Neoplasm Study

Author

Parmar, MKB, Torri, V, Bonaventura, A, Bonazzi, C, Delaloye, J, Marsoni, S, Mangioni, C, Sandercock, J, Sessa, C, Williams, C, Tinazzi, A, Flann, M, Geiser, K, Scorpiglione, N, Stewart, J, Chaves, J, Palmeiro, E, Curtain, A, McCormack, T, Gennatas, C, Marras, F, Oppo, T, Balestrino, M, Malzoni, C, Malzoni, M, Belli, M, Geminiani, M, Crestani, G, Monaco, A, Vavala, V, Piatto, E, Barattini, G, Fornara, P, Chetri, M, Santeufemia, G, Artioli, F, Carone, D, Fanizza, G, Trentadue, R, Priolo, D, Scollo, P, Nigro, S, Petrina, M, Mastrantonio, P, Spanna, G, Zagni, R, Belloni, C, Colleoni, R, Redaelli, L, Cavagnini, A, Di Costanzo, G, Perroni, D, Arienti, S, Orfanotti, G, Cantoni, F, Secli, R, Bianchi, A, Martinello, R, Mollica, G, Maizzi, D, Picchiarelli, M, Fiorini, G, Borsani, M, Colombo, E, Garsia, S, Melgrati, L, Paggi, G, Brunenghi, G, Casini, M, Isa, L, Algeri, R, Prozio, G, Belfiore, G, Angelini, F, D'Aprile, M, Moreschi, M, Mauri, M, Natale, N, Senzani, F, Pavanato, G, Poggi, G, Garuti, G, Luerti, M, Cruciani, G, Pagano, F, Baccolo, M, Poddi, E, Bocciolone, L, Sabelli, M, Maggi, R, Restelli, C, D'Antona, A, Locatelli, M, Pessi, A, Raina, A, Chiari, S, Gabriele, A, Pittelli, M, Iacobelli, P, Dogliotti, L, Gorzegno, G, Musso, P, Vegna, G, Coco, G, Alletti, D, Picciotto, F, Lucchese, V, Epis, A, di Palumbo, V, Drudi, G, Ravaioli, A, Zampella, D, Morandi, M, Gorga, G, Zucchelli, C, Cariello, S, Galletto, L, Sussio, M, Massacesi, L, Massacesi, M, Carli, A, Tucci, E, Tajani, E, Corrado, G, Bumma, S, Durando, A, Massobrio, M, Sberveglieri, M, Biasio, M, Guercio, E, Jura, R, Danese, S, Wierdis, T, Farnelli, C, Tarantino, G, Grassi, R, Repetti, F, Rocchi, B, Grampa, M, Ercoli, A, Griso, C, Signori, E, Zanini, L, Presti, M, Klimek, M, Urbanski, K, Biswas, A, Viegas, O, Kochli, O, Dreher, E, Fey, M, Beck, G, Ludin, J, Bonnefoi, H, Krauer, F, Bauer, J, Delmore, G, Furrer, C, Lorenz, U, Thurlimann, B, Bronz, L, Sanna, P, Wyss, D, Goldhirsch, A, Gyr, T, Leidi, L, Pastorelli, G, Pagani, O, Rey, P, Hailer, U, Benz, J, Kaye, S, Reed, N, Symonds, R, Atkinson, R, Axford, A, Rustin, G, Seckl, M, Green, J, Scott, I, Guthrie, D, Harper, P, Calman, F, Dobbs, H, Weir, P, Cassoni, A, Lederman, J, Souhami, R, Bozzino, J, Adab, F, Redman, C, Scoble, J, Paterson, M, Daniel, F, Cowley, N, Spooner, D, Hong, A, McIllmurray, M, Hendy Ibbs, P, Hall, V, Iveson, T, Whitehouse, J, Garry, R, Lamont, A, Robinson, A, Trask, C, Clubb, A, Murrell, D, Newman, G, Wilkins, M, Goldthorp, W, Roberts, J, Radstone, D, Whipp, M, Ledermann, J, Pater, J, Buyse, M, Omura, G., COLOMBO, NICOLETTA, Parmar, M, Torri, V, Bonaventura, A, Bonazzi, C, Colombo, N, Delaloye, J, Marsoni, S, Mangioni, C, Sandercock, J, Sessa, C, Williams, C, Tinazzi, A, Flann, M, Geiser, K, Scorpiglione, N, Stewart, J, Chaves, J, Palmeiro, E, Curtain, A, Mccormack, T, Gennatas, C, Marras, F, Oppo, T, Balestrino, M, Malzoni, C, Malzoni, M, Belli, M, Geminiani, M, Crestani, G, Monaco, A, Vavala, V, Piatto, E, Barattini, G, Fornara, P, Chetri, M, Santeufemia, G, Artioli, F, Carone, D, Fanizza, G, Trentadue, R, Priolo, D, Scollo, P, Nigro, S, Petrina, M, Mastrantonio, P, Spanna, G, Zagni, R, Belloni, C, Colleoni, R, Redaelli, L, Cavagnini, A, Di Costanzo, G, Perroni, D, Arienti, S, Orfanotti, G, Cantoni, F, Secli, R, Bianchi, A, Martinello, R, Mollica, G, Maizzi, D, Picchiarelli, M, Fiorini, G, Borsani, M, Colombo, E, Garsia, S, Melgrati, L, Paggi, G, Brunenghi, G, Casini, M, Isa, L, Algeri, R, Prozio, G, Belfiore, G, Angelini, F, D'Aprile, M, Moreschi, M, Mauri, M, Natale, N, Senzani, F, Pavanato, G, Poggi, G, Garuti, G, Luerti, M, Cruciani, G, Pagano, F, Baccolo, M, Poddi, E, Bocciolone, L, Sabelli, M, Maggi, R, Restelli, C, D'Antona, A, Locatelli, M, Pessi, A, Raina, A, Chiari, S, Gabriele, A, Pittelli, M, Iacobelli, P, Dogliotti, L, Gorzegno, G, Musso, P, Vegna, G, Coco, G, Alletti, D, Picciotto, F, Lucchese, V, Epis, A, di Palumbo, V, Drudi, G, Ravaioli, A, Zampella, D, Morandi, M, Gorga, G, Zucchelli, C, Cariello, S, Galletto, L, Sussio, M, Massacesi, L, Massacesi, M, Carli, A, Tucci, E, Tajani, E, Corrado, G, Bumma, S, Durando, A, Massobrio, M, Sberveglieri, M, Biasio, M, Guercio, E, Jura, R, Danese, S, Wierdis, T, Farnelli, C, Tarantino, G, Grassi, R, Repetti, F, Rocchi, B, Grampa, M, Ercoli, A, Griso, C, Signori, E, Zanini, L, Presti, M, Klimek, M, Urbanski, K, Biswas, A, Viegas, O, Kochli, O, Dreher, E, Fey, M, Beck, G, Ludin, J, Bonnefoi, H, Krauer, F, Bauer, J, Delmore, G, Furrer, C, Lorenz, U, Thurlimann, B, Bronz, L, Sanna, P, Wyss, D, Goldhirsch, A, Gyr, T, Leidi, L, Pastorelli, G, Pagani, O, Rey, P, Hailer, U, Benz, J, Kaye, S, Reed, N, Symonds, R, Atkinson, R, Axford, A, Rustin, G, Seckl, M, Green, J, Scott, I, Guthrie, D, Harper, P, Calman, F, Dobbs, H, Weir, P, Cassoni, A, Lederman, J, Souhami, R, Bozzino, J, Adab, F, Redman, C, Scoble, J, Paterson, M, Daniel, F, Cowley, N, Spooner, D, Hong, A, Mcillmurray, M, Hendy Ibbs, P, Hall, V, Iveson, T, Whitehouse, J, Garry, R, Lamont, A, Robinson, A, Trask, C, Clubb, A, Murrell, D, Newman, G, Wilkins, M, Goldthorp, W, Roberts, J, Radstone, D, Whipp, M, Ledermann, J, Pater, J, Buyse, M, and Omura, G

Subjects
Antineoplastic Combined Chemotherapy Protocol, Ovarian Neoplasm, Alopecia, Leukopenia, Middle Aged, Thrombocytopenia, Carboplatin, Antineoplastic Agent, Doxorubicin, Proportional Hazards Model, Female, Survival Analysi, Cisplatin, Cyclophosphamide, Aged, Human
Abstract

A series of meta-analyses of randomised controlled trials raised the question of whether the three-drug combination of CAP (cyclophosphamide, doxorubicin, and cisplatin) was more or less effective than optimal-dose single-agent carboplatin for women with advanced ovarian cancer.

Published
1998

44. Antibodies elicited by naked DNA vaccination against hypervariable VH-CDR3 idiotypic determinants of B-lymphoproliferative disorders specifically react with patients? tumor cells

Author

Rinaldi M., Ria F., Parrella P., Signori E., Serra A., Ciafrè S.A., Vespignani I., Lazzari M., Farace M.G., Saglio G., and Fazio V.M.

Subjects
B-lymphoma, idiotypic determinants, DNA vaccination
Abstract

Several reports have suggested that the mechanism of protection induced by antiidiotypic vaccination against low-grade lymphoproliferative disorders is likely to be antibody mediated.Here we test the hypothesis that DNA vaccination with the short peptide encompassing the complementary-determining region 3 hypervariable region of immunoglobulin heavy chain (VH-CDR3) may elicit a specific antibody immune response able to recognize the native antigens in the form required for therapy. As a test system, we used the VH-CDR3 sequences derived from two patients with non-Hodgkin's B lymphomas (PA, AS) and one patient with hairy cell leukemia (BA) to immunize outbred Swiss mice. This experimental model could mimic a clinical setting in which different patients present distinct HLA haplotypes. Individual tumor-specific VH-CDR3 sequences were amplified by a two-step procedure and directly cloned into multigenic plasmid vectors (pRC100 and derived) with and without mouse interleukin 2 (mIL-2). Each tumor-specific sequence was characterized by sequencing. Female Swiss mice were vaccinated i.m. with plasmids expressing the tumor-specific VH-CDR3 sequence alone (pRC101-PA), mIL-2 plus the VH-CDR3 sequence (pRC111-PA), or a different unrelated antigen (NS3 of hepatitis C virus; pRC112), the sole mIL-2 (pRC110), and the empty plasmid (pRC100). Boost injections were performed at 3 and 16 weeks from the first vaccination, and sera were drawn before each vaccination and at 6, 9, and 19 weeks. Induction of anti-VH-CDR3s antibodies in the sera and their ability to recognize native antigens on patients' tumor cells were evaluated by FACS analysis. Up to 56% (n = 25) of mice vaccinated with pRC111-PA plasmid and 20% (n = 15) of mice vaccinated with pRC101-PA developed a specific immune response that was maintained throughout 19 weeks of observation in 40% of pRC111-PA-vaccinated mice. No response was detected in sera obtained from mice vaccinated with the other plasmids (n = 45). pRC111-PA injection s.c. was less effective (13%, n = 15) than i.m. injection (53%, n = 15). Indeed, we demonstrated that antibodies elicited by naked DNA vaccination against three different patient-derived VH-CDR3 peptides (pRC111-PA or BA or AS) readily reacted with binding epitopes on the idiotypic proteins expressed on the surface of tumor cells derived from each patient; 60, 40, and 40% of, respectively, PA-, BA-, and AS-vaccinated mice developed specific antibodies. No cross-reactivity was detected among the three different CDR3s against tumor cells derived from the other two patients. The outbred mouse strategy confirmed the significant matching potential of three different VH-CDR3 peptides to be efficaciously presented through different MHCs. We conclude that individual VH-CDR3 DNA vaccination can result in a potentially effective specific immune response against non-Hodgkin's B lymphoma cells by a rapid and low-cost therapeutic approach.

Published
2001

45. Antibodies elicited by naked DNA vaccination against the complementary-determining region 3 hypervariable region of immunoglobulin heavy chain idiotipic determinants of B-lymphoproliferative disorders specifically react with patient's tumor cells

Author

Rinaldi, M., Ria, F., Parrella, P., Signori, E., Serra, A., Ciafrè, S. A., Vespignani, I., Lazzari, M., Farace, M. G., Saglio, G., and Vito Michele Fazio

Subjects
Lymphoma, B-Cell, Lymphoma, Antibodies, Neoplasm, Hairy Cell, Genetic Vectors, Molecular Sequence Data, Immunoglobulin Variable Region, Immunoglobulin Idiotypes, Epitopes, Base Sequence, Cell Line, Transformed, Animals, Leukemia, Hairy Cell, Humans, Complementarity Determining Regions, Flow Cytometry, Interleukin-2, Antibodies, Anti-Idiotypic, Mice, Cancer Vaccines, Vaccines, DNA, Amino Acid Sequence, Immunoglobulin Heavy Chains, Leukemia, B-Cell, Antibodies, Cell Line, Settore MED/04 - PATOLOGIA GENERALE, Vaccines, Leukemia, Settore BIO/13, B-Cell, DNA, Anti-Idiotypic, Transformed, Neoplasm
Abstract

Several reports have suggested that the mechanism of protection induced by antiidiotypic vaccination against low-grade lymphoproliferative disorders is likely to be antibody mediated. Here we test the hypothesis that DNA vaccination with the short peptide encompassing the complementary-determining region 3 hypervariable region of immunoglobulin heavy chain (VH-CDR3) may elicit a specific antibody immune response able to recognize the native antigens in the form required for therapy. As a test system, we used the VH-CDR3 sequences derived from two patients with non-Hodgkin's B lymphomas (PA, AS) and one patient with hairy cell leukemia (BA) to immunize outbred Swiss mice. This experimental model could mimic a clinical setting in which different patients present distinct HLA haplotypes. Individual tumor-specific VH-CDR3 sequences were amplified by a two-step procedure and directly cloned into multigenic plasmid vectors (pRC100 and derived) with and without mouse interleukin 2 (mIL-2). Each tumor-specific sequence was characterized by sequencing. Female Swiss mice were vaccinated i.m. with plasmids expressing the tumor-specific VH-CDR3 sequence alone (pRC101-PA), mIL-2 plus the VH-CDR3 sequence (pRC111-PA), or a different unrelated antigen (NS3 of hepatitis C virus; pRC112), the sole mIL-2 (pRC110), and the empty plasmid (pRC100). Boost injections were performed at 3 and 16 weeks from the first vaccination, and sera were drawn before each vaccination and at 6, 9, and 19 weeks. Induction of anti-VH-CDR3s antibodies in the sera and their ability to recognize native antigens on patients' tumor cells were evaluated by FACS analysis. Up to 56% (n = 25) of mice vaccinated with pRC111-PA plasmid and 20% (n = 15) of mice vaccinated with pRC101-PA developed a specific immune response that was maintained throughout 19 weeks of observation in 40% of pRC111-PA-vaccinated mice. No response was detected in sera obtained from mice vaccinated with the other plasmids (n = 45). pRC111-PA injection s.c. was less effective (13%, n = 15) than i.m. injection (53%, n = 15). Indeed, we demonstrated that antibodies elicited by naked DNA vaccination against three different patient-derived VH-CDR3 peptides (pRC111-PA or BA or AS) readily reacted with binding epitopes on the idiotypic proteins expressed on the surface of tumor cells derived from each patient; 60, 40, and 40% of, respectively, PA-, BA-, and AS-vaccinated mice developed specific antibodies. No cross-reactivity was detected among the three different CDR3s against tumor cells derived from the other two patients. The outbred mouse strategy confirmed the significant matching potential of three different VH-CDR3 peptides to be efficaciously presented through different MHCs. We conclude that individual VH-CDR3 DNA vaccination can result in a potentially effective specific immune response against non-Hodgkin's B lymphoma cells by a rapid and low-cost therapeutic approach.

Published
2001

47. Strategies to elicit anti-idiotypic immune response in B-lymphoma patients. Peptide and genetic immunization

Author

Rinaldi M, Sa, Ciafrè, Parrella P, Signori E, Mg, Farace, Saglio G, and Vito Michele Fazio

Subjects
Vaccines, Lymphoma, B-Cell, Lymphoma, Genes, Immunoglobulin, Settore BIO/13, B-Cell, Gene Therapy, DNA, Genetic Therapy, Cancer Vaccines, Antibodies, Antibodies, Anti-Idiotypic, Immunotherapy, Antibody Formation, Vaccines, DNA, Immunoglobulin Heavy Chains, Humans, Anti-Idiotypic, Genes, Immunoglobulin
Published
1999

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