A recombinant vaccinia virus containing the papilloma E2 protein promotes tumor regression by stimulating macrophage antibody-dependent cytotoxicity

Rosales, Carlos; Valadéz-Graham, Viviana; Rosas, Gerardo Arrellín; Merchant, Hugo; Rosales, Ricardo

doi:10.1007/s002620000125

Cited by 40 publications

(41 citation statements)

References 40 publications

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“…This effect will also contribute to expose other cell antigens and then generate a wider immune response against the tumor cells. 3,4 The overall result of this immune response is the regression of papiloma-induced tumors. In the present work, we found that all MVA E2-treated patients developed an immune response against cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…MVA E2 was shown to stop human tumor growth in mice and also to induce tumor regression in tumor-bearing rabbits. 3,4 More recently, MVA E2 was also shown to induce elimination of pre-cancerous lesions CIN 1 and CIN 2. 5 To further evaluate the therapeutic potential of the MVA E2 recombinant vaccine on high grade (CIN 3 lesions), we undertook this Phase II clinical trial with 54 female patients.…”

Section: Introductionmentioning

confidence: 99%

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Regression of papilloma high-grade lesions (CIN 2 and CIN 3) is stimulated by therapeutic vaccination with MVA E2 recombinant vaccine

et al. 2006

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Human papillomavirus (HPV) is the etiologic agent for cervical cancer. In Mexico, a women dies every 2 h, and since 1990 the statistics have shown that the numbers of deaths are increasing. We conducted a phase II clinical trial to evaluate the potential use of the MVA E2 recombinant vaccinia virus in treating high-grade lesions (CIN 2 and CIN 3) associated with oncogenic papillomavirus. Fifty-four female patients with high degree lesions were treated either with an MVA E2 therapeutic vaccine or with conization. Thirty-four women received the therapeutic vaccine, at a total of 10 7 virus particles per dose injected directly into the uterus once every week over a 6-week period. Twenty control patients were treated with conization. By colposcopy, 19 patients out of 34 showed no lesion, in three patients the lesions were reduced by 85-90%, in eight other lesions had reduced by 60%, and in four more patients, they were reduced by 25%. Histological analysis showed total elimination of high-grade lesions in 20 out of 34 patients after treatment with MVA E2. Eleven patients had a 50% reduction in lesion size. In two other patients, the lesion was reduced to CIN 2 and in one more patient the lesion was reduced to low grade (CIN 1). All patients developed antibodies against the MVA E2 vaccine, and generated a specific cytotoxic response against papilloma-transformed cells. DNA viral load was significantly reduced in MVA E2-treated patients. Conization eliminated the lesions in 80% of the patients, but patients did not develop cytotoxic activity specific against cancer cells and did not eliminate the papillomavirus. In addition, three patients treated with conization had recurrence of lesions 1 year later. These results show that therapeutic vaccination with MVA E2 proved to be very effective in stimulating the immune system against papillomavirus, and in generating regression of high-grade lesion.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Regression of papilloma high-grade lesions (CIN 2 and CIN 3) is stimulated by therapeutic vaccination with MVA E2 recombinant vaccine

et al. 2006

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“…42,44,46,57 -59 In some of those studies, costimulatory molecules or cytokines were used to enhance vaccine effects. 44,45,59,64 These studies have suggested a role for antibodies, 36 -41,43,47,48,51 -53,60,63,64 CTL, 36 -48 and delayed-type hypersensitive T cells, 36,37,46,53 although the role of these factors was not directly demonstrated by in vivo cell depletion or adoptive cell transfer. The mouse models targeting human carcinoembryonic Ag (CEA ) and MUC-1 with VV vaccines, 36,39 -41,43,45 -48,52,63 similar to the human GA733 model used in the present study, include Ags that are expressed by tumors and by normal tissues.…”

Section: Cancer Gene Therapymentioning

confidence: 99%

Inhibition of tumor growth by recombinant vaccinia virus expressing GA733/CO17-1A/EpCAM/KSA/KS1-4 antigen in mice

Žaloudík

Jacob

et al. 2002

Cancer Gene Ther

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The human colorectal carcinoma ( CRC ) -associated GA733 antigen ( Ag ), also named CO17 -1A / EpCAM / KSA / KS1 -4, has been a useful target in passive immunotherapy of CRC patients with monoclonal antibody ( mAb ) and in active immunotherapy with antiidiotypic antibodies or with recombinant protein. These approaches have targeted single epitopes ( monoclonal anti -GA733 antibodies and anti -idiotypic antibodies ) or extracellular domain epitopes ( recombinant protein ), primarily by B cells. To determine whether a reagent that induces immunity to a larger number of both B -and T -cell epitopes might represent a superior vaccine, we analyzed the capacity of full -length GA733 Ag expressing multiple potentially immunogenic epitopes and encoded by recombinant vaccinia virus ( VV GA733 -2 ) to induce humoral, cellular, and / or protective immunity in mice. VV GA733 -2 induced Ag -specific antibodies that reacted predominantly to unknown epitopes on the Ag and lysed Ag -positive CRC targets in conjunction with murine peritoneal macrophages as effector cells. Immunized mice developed Ag -specific, proliferative and delayed -type hypersensitive lymphocytes. VV GA733 -2 inhibited growth of ras -transformed syngeneic tumor cells expressing the human GA733 Ag in mice. These results suggest the potential of VV GA733 -2 as a candidate vaccine for patients with CRC, possibly in combination with recombinant GA733 -2 -expressing adenovirus, which has been shown to induce cytolytic antibodies and T cells as well as tumor protective effects in mice. The combined vaccine approach may be superior to the use of either vaccine alone in patients who are pre -immune to both viruses.

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“…10 Therefore, E2 and E7 provide attractive targets for a therapeutic vaccine with treatment ranging from low-grade diseases, such as CIN, VIN and AIN to malignant carcinoma. 11,12 Vaccine strategies targeting E6 and E7, using peptides, 13 proteins, 14 viral vectors 15 and plasmid DNA, 16,17 have been reported. However, there is only limited information on the CD8 1 T cell response to HPV E2.…”

mentioning

confidence: 99%

“…11,12 Vaccine strategies targeting E6 and E7, using peptides, 13 proteins, 14 viral vectors 15 and plasmid DNA, 16,17 have been reported. However, there is only limited information on the CD8 1 T cell response to HPV E2.…”

mentioning

confidence: 99%

Combined prophylactic and therapeutic cancer vaccine: Enhancing CTL responses to HPV16 E2 using a chimeric VLP in HLA‐A2 mice

Qian

Dong

Pang³

et al. 2006

Intl Journal of Cancer

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We identified the strategies to induce a CTL response to human papillomavirus (HPV) 16 E2 in HLA-A2 transgenic mice (AAD). A chimeric HPV16 virus-like particle (VLP) that includes full length HPV16 E7 and E2 (VLP-E7E2) was generated. The combination of E2 and E7 has the advantage that E2 is expressed in early dysplasia and neoplasia lesions, where E7 is expressed in more advance lesions. Since T cell response to E2 is less defined, we first evaluated the strategies to enhancing CD8 1 T cell responses to HPV E7, using different combinations of immune-modulators with VLP-E7E2. Data showed that the CTL response to E7 could be significantly enhanced by coinjection of GM-CSF and antiCD40 antibodies with chimeric VLP-E7E2 without adjuvant. However, using the same combination, a low level of CD8 1 T cell response to E2 was detected. To enhance the CD81 T cell response to E2, we analyzed T cell epitopes from E2 sequence. A heterogonous prime-boost with chimeric VLP-E7E2 and E2 peptides was performed. The data showed that the priming with chimeric VLP-E7E2, followed by boosting with E2 peptides, gave a better CTL response than 2 immunizations with E2 peptides. The enhanced immunity is due to the increase of CD11c 1 and CD11c 1 CD40 1 double positive dendritic cells in mice that received immune-modulators, GM-CSF and antiCD40. Furthermore, the level of anti-L1 antibodies remains similar in mice immunized with chimeric VLP with/without immune-modulators. Thus, the data suggested that the chimeric VLP-E7E2 has a therapeutic potential for the treatment of HPV-associated CINs and cancer without diminishing VLPs potential as a prophylactic vaccine by inducing anti-L1 antibodies against free virus. ' 2006 Wiley-Liss, Inc.Key words: vaccine; HPV 16; CTL; chimeric VLP; HPV 16 E2; dendritic cells Human papillomavirus infections are associated with a spectrum of epithelial diseases from benign warts to cervical intraepithelial neoplasia (CIN) to invasive carcinoma. Almost all cervical cancers are caused by HPV infection, most often HPV16.1 Therefore, the development of effective HPV vaccines could contribute greatly to the prevention and treatment of cervical neoplasia and other diseases caused by HPV infection. Substantial advances have been made in developing HPV prophylactic vaccines based on L1 virus-like particles that induce neutralizing antibodies to L1. [2][3][4][5] In contrast, therapeutic HPV vaccines have not yet demonstrated high efficacy against cervical cancer or premalignant HPVinduced neoplasia in clinical trials.6 Humoral base vaccine is essential to eradication of HPV infection in uninfected population. However, for the population with HPV exposure, a combined prophylactic/therapeutic vaccine would be an essential development. It could promote mass immunization programs of both preadolescent and older women, many of whom have already been exposed to genital tract HPV infection. A combined vaccine could offer the best combination of immediate impact and long-term effectiveness. It will be particularly useful in dev...

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A recombinant vaccinia virus containing the papilloma E2 protein promotes tumor regression by stimulating macrophage antibody-dependent cytotoxicity

Cited by 40 publications

References 40 publications

Regression of papilloma high-grade lesions (CIN 2 and CIN 3) is stimulated by therapeutic vaccination with MVA E2 recombinant vaccine

Regression of papilloma high-grade lesions (CIN 2 and CIN 3) is stimulated by therapeutic vaccination with MVA E2 recombinant vaccine

Inhibition of tumor growth by recombinant vaccinia virus expressing GA733/CO17-1A/EpCAM/KSA/KS1-4 antigen in mice

Combined prophylactic and therapeutic cancer vaccine: Enhancing CTL responses to HPV16 E2 using a chimeric VLP in HLA‐A2 mice

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