Dendritic cell-based tumor vaccine for cervical cancer II: results of a clinical pilot study in 15 individual patients

Ferrara, Alfonso Massimiliano; Nonn, Marion; Sehr, Peter; Schreckenberger, Carola; Pawlita, Michael; Dürst, Matthias; Schneider, Achim; Kaufmann, Andreas M.

doi:10.1007/s00432-003-0463-5

Cited by 119 publications

(73 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, these vaccines are easily produced, are chemically stable, and are devoid of oncogenic potential as well as free of bacterial/viral contaminating substances, hereby avoiding the antigenic competition often seen against viral vector-based vaccines expressing tumor-associated antigens or HIV antigens (19, 34 -36) or between simultaneously injected antigens such as is the case with fusion protein or gene products (20 -22). Other approaches at therapeutic vaccination in cancer include administration of antigen-loaded dendritic cells; however, this requires specialized laboratories that prepare autologous dendritic cells for each individual patient (37,38).…”

Section: Discussionmentioning

confidence: 99%

Phase I Immunotherapeutic Trial with Long Peptides Spanning the E6 and E7 Sequences of High-Risk Human Papillomavirus 16 in End-Stage Cervical Cancer Patients Shows Low Toxicity and Robust Immunogenicity

Kenter¹,

Welters

Valentijn

et al. 2008

Clinical Cancer Research

282

204

View full text Add to dashboard Cite

Purpose: To determine the toxicity, safety, and immunogenicity of a human papillomavirus 16 (HPV16) E6 and E7 long peptide vaccine administered to end-stage cervical cancer patients. Experimental Design:Three groups of end-stage cervical cancer patients (in total n = 35) were s.c. vaccinated with HPV16 E6 combined with or separated from HPV16 E7 overlapping long peptides in Montanide ISA-51 adjuvant, four times at 3-week intervals. Group 1 received 300 Ag/ peptide at a single site and group 2 received 100 Ag/peptide of the E6 peptides in one limb and 300 Ag/peptide of the E7 peptides in a second limb. Group 3 received separate injections of E6 and E7 peptides, each at a dose of 50 Ag/peptide. The primary end point was to determine safety and toxicity of the HPV16 long peptides vaccine. In addition, the vaccine-induced T-cell response was assessed by IFNg enzyme-linked immunospot. Results: No toxicity beyond grade 2 was observed during and after four vaccinations. In a few patients, transient flu-like symptoms were observed. Enzyme-linked immunospot analysis of the vaccine-induced immune response revealed that coinjection of the E6 and E7 peptides resulted in a strong and broad T-cell response dominated by immunity against E6. Injection of the E6 and E7 peptides at two different sites increased the E7 response but did not affect the magnitude of the E6-induced immune response. Conclusions: The HPV16 E6 and E7 long peptide-based vaccine is well tolerated and capable of inducing a broad IFNg-associated T-cell response even in end-stage cervical cancer patients.Close to 100% cervical cancers are caused by persistent infection with high-risk human papillomaviruses (HPV; ref. 1). Of the different high-risk HPV types that can cause cervical cancer (2), HPV16 alone is responsible worldwide for more than half of all cases of cervical cancer (1, 2). Genital infection with high-risk HPV is very common and normally cleared within 1 year. However, in a minority (f1%) of the infected individuals, the HPV persists, ultimately resulting in genital neoplastic lesions.Currently, a preventive HPV vaccine is on the market, which effectively prevents this persistent infection and associated disease by the induction of neutralizing antibodies against the envelope proteins of HPV16 and HPV18, the HPV type second on the list of most frequent HPV types associated with cancer. Although these vaccines are very efficient in the prevention of persistent infection by HPV16 and HPV18 (3 -8) and have potential for prevention of cervical intraepithelial neoplasia (9 -11), there is no evidence for efficacy against established .It is generally accepted that virus-infected cells can only be effectively dealt with by cell-mediated adaptive T-cell immunity. Consequently, immunotherapy capable of inducing robust HPV16-specific T-cell immunity is highly desirable for eradication of established HPV16 infection and diseases caused thereby, such as cervical intraepithelial neoplasia, vulvar intraepithelial neoplasia, cervical cancer, other anoge...

show abstract

Section: Discussionmentioning

confidence: 99%

Phase I Immunotherapeutic Trial with Long Peptides Spanning the E6 and E7 Sequences of High-Risk Human Papillomavirus 16 in End-Stage Cervical Cancer Patients Shows Low Toxicity and Robust Immunogenicity

Kenter¹,

Welters

Valentijn

et al. 2008

Clinical Cancer Research

282

204

View full text Add to dashboard Cite

show abstract

“…Dendritic cell-based immunotherapy applied to patients with SCC is quite uncommon in humans; DC vaccination is performed in patients with cervical cancer (including SCC) by targeting papilloma virus oncoprotein E7 as a tumor-specific antigen [7]. There have been no reports of DC-based immunotherapy in dogs.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Dendritic Cell-Mediated Immune Responses among Canine Malignant Cells

Tamura

Arai

Ueno

et al. 2007

The Journal of Veterinary Medical Science

View full text Add to dashboard Cite

ABSTRACT. Dendritic cell (DC) vaccination is one of the most attractive immunotherapies for malignancies in dogs. To examine the differences in DC-mediated immune responses from different types of malignancies in dogs, we vaccinated dogs using autologous DCs pulsed with keyhole limpet hemocyanin (KLH) and cell lysate prepared from squamous cell carcinoma SCC2/88 (SCC-KLH-DC), histiocytic sarcoma CHS-5 (CHS-KLH-DC), or B cell leukemia GL-1 (GL-KLH-DC) in vitro. In vivo inductions of immune responses against these tumor cells were compared by the delayed-type hypersensitivity (DTH) skin test. The DTH response against SCC2/88 cells were observed in dogs vaccinated with autologous SCC-KLH-DC, while the response was undetectable against CHS-5 and GL-1 cells in dogs vaccinated with autologous CHS-KLH-DC and GL-KLH-DC. Skin biopsies taken from DTH challenge sites were then examined for immunohistochemistry, and recruitment of CD8 and CD4 T cells was detected at the site where SCC2/88 cells were inoculated in dogs vaccinated with SCC-KLH-DC. By contrast, neither CD8 nor CD4 T cell infiltration was found at the DTH challenge site in the dogs vaccinated with CHS-KLH-DC or GL-KLH-DC. These findings may reflect that the efficacy of immune induction by DC vaccination varies among tumor types and that immune responses could be inducible in squamous cell carcinoma. Our results encouraged further investigation of therapeutic vaccination for dogs with advanced squamous cell carcinoma in clinical trials. KEY WORDS: canine, delayed-type hypersensitivity, dendritic cell, malignancies, vaccination.J. Vet. Med. Sci. 69(9): 925-930, 2007 Dendritic cells (DCs) are the most potent antigen-presenting cells for initiating cellular immune responses through the activation of naïve T lymphocytes [3,20], making them the most attractive immunoregulatory cells for tumor immunotherapy. Recently, many clinical trials have been conducted on human patients with various types of tumors to evaluate the feasibility of immunization with DC vaccination, in which autologous DCs are loaded with defined tumor antigen such as synthetic peptide [19] and nucleotideencoding tumor antigen [10] or whole antigenic preparations such as tumor cell lysate [1]. These DC vaccinations have been proven to be effective for the induction of antitumor immunities and clinical responses in patients with several types of malignancies such as lymphoma [13,22], renal and prostate carcinoma [5,12], and especially melanoma [4,11]; however, the effectiveness of DC vaccination varies among tumor types. For example, some types of malignancies such as gastrointestinal malignancies, including colorectal, gastric, and hepatocellular carcinoma, are still not sufficient to show anti-tumor therapeutic effect [6,17]; nevertheless, the protocol of DC vaccination, including preparation of DC, loading antigen(s) to DC, and route of DC administration, are not yet well standardized to compare with other trials in different types of tumor.We have previously reported the in vivo induction of i...

show abstract

“…Earlier studies showed that autologous DCs loaded with HPV E7 protein could induce in vitro a speciic T cell responses [123], and T cell proliferative responses in vivo, [124]. Another study found E7-speciic γ-IFN secreting CD8+ T cells in patients treated with autologous DCs pulsed with HPV E7 [125], or with HPV E7 protein and keyhole limpet hemocyanin (KLH) [126].…”

Section: Dendritic Cell-based Vaccinesmentioning

confidence: 99%

Prophylactic and Therapeutic Vaccines against Human Papillomavirus Infections

Rosales¹,

Rosales²

2017

Vaccines

View full text Add to dashboard Cite

Human papillomaviruses (HPVs) are a large family of double-strand DNA viruses comprising more than 180 types. Infection with HPV is associated with benign and malignant proliferation of skin and mucosae. Low-risk HPVs produce warts, whereas high-risk viruses induce tumors. Because there are no anti-viral drugs for HPV infection, there is a lot of interest in vaccines that can prevent the infection and also in vaccines that can be used to treat established infections and HPV-related tumors. Two prophylactic vaccines have been approved for preventing HPV infection. They seem to be efective when very young people are vaccinated. Unfortunately, many older people are still at risk of infection, mainly in countries where vaccination coverage is not eicient and for those people, novel therapeutic vaccines are being developed. This chapter describes the properties of HPV vaccines used today and the current status of several therapeutic vaccines been developed to treat HPV-induced lesions.

show abstract

Dendritic cell-based tumor vaccine for cervical cancer II: results of a clinical pilot study in 15 individual patients

Abstract: Autologous dendritic cells pulsed with HPV E7 protein can induce T cell responses in a portion of late stage cervical cancer patients. Boosting of immune responses by adjuvants and vaccination of tumor HLA-positive patients will be mandatory in future trials.

Cited by 119 publications

References 34 publications

Phase I Immunotherapeutic Trial with Long Peptides Spanning the E6 and E7 Sequences of High-Risk Human Papillomavirus 16 in End-Stage Cervical Cancer Patients Shows Low Toxicity and Robust Immunogenicity

Phase I Immunotherapeutic Trial with Long Peptides Spanning the E6 and E7 Sequences of High-Risk Human Papillomavirus 16 in End-Stage Cervical Cancer Patients Shows Low Toxicity and Robust Immunogenicity

Comparison of Dendritic Cell-Mediated Immune Responses among Canine Malignant Cells

Prophylactic and Therapeutic Vaccines against Human Papillomavirus Infections

Contact Info

Product

Resources

About