From: "Dr. D. Kossove" <doctordee@telkomsa.net>
To: "sharon anderson"
Subject: Vaccination with Predesignated or Evidence-Based Peptides for Patients with Recurrent Gynecologic Cancers.
Date: Sunday, January 18, 2004 2:46 AM

Vaccination with Predesignated or Evidence-Based Peptides for Patients with Recurrent Gynecologic Cancers.

http://www.immunotherapy-journal.com/pt/re/jimmuno/abstract.00002371-200401000-00006.htm;jsessionid=AJcS7J0Fv8UoMB4ONUSzojv2RCEN9tJI3rnt5v3utYSAcflYhV7G!-59175566

  

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Journal of Immunotherapy: Volume 27(1) January/February 2004 pp 60-72 
Vaccination with Predesignated or Evidence-Based Peptides for Patients with Recurrent Gynecologic Cancers
Tsuda, Naotake MD, PhD*; Mochizuki, Kazuo MD*; Harada, Mamoru MD, PhD; Sukehiro, Aki; Kawano, Koichiro MD, PhD*; Yamada, Akira PhD; Ushijima, Kimio MD, PhD*; Sugiyama, Toru MD, PhD*; Nishida, Takashi MD, PhD*; Yamana, Hideaki MD, PhD; Itoh, Kyogo MD, PhD; Kamura, Toshiharu MD, PhD*

From the Departments of *Obstetrics and Gynecology, Immunology, and Surgery, Kurume University School of Medicine, Kurume, Fukuoka, Japan.

Received January 26, 2003; accepted August 4, 2003.

Reprints: Mamoru Harada, Department of Immunology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan; E-mail: haramamo@med.kurume-u.ac.jp.

Supported in part by Grants-in-Aid from the Ministry of Education, Science, Sports, and Culture of Japan (no. 12213134 to K.I.), and from the Ministry of Health and Welfare of Japan (no. H14-trans-002, 11-16, and H12-cancer-004 to K.I.).

Abstract:
Two different trials of peptide vaccination were conducted for patients with recurrent gynecologic cancers. In the first regimen, four HLA-A24+ patients (two with cervical cancer and two with ovarian cancer) were vaccinated with peptides that were predesignated before vaccination. Three patients exhibited with a grade 1 adverse effect, and no clinical response was observed in any patients. In the second regimen, six HLA-A24+ and four HLA-A2+ patients (five with cervical cancer, one with endometrial cancer, one with uterine sarcoma, and three with ovarian cancer) were vaccinated with peptides (maximum four) to which preexisting cytotoxic T lymphocyte precursors in the periphery were confirmed before vaccination. With this regimen, grade 1 adverse effects were observed in eight patients, a grade 2 adverse effect in one patient, and a grade 3 adverse effect (ie, rectal bleeding) in one patient. However, this regimen was able to enhance peptide-specific cytotoxic T lymphocytes in seven of ten patients, and three of five cervical cancer patients showed objective tumor regression. Analysis of immunoglobulin G -reactive to administered peptides suggested that the induction of peptide-specific immunoglobulin G was correlated with clinical responses. Overall, these results suggest that peptide vaccination of patients showing evidence of preexisting peptide-specific cytotoxic T lymphocyte precursors could be superior to vaccination with predesignated peptides, and that the evidence-based regimen is applicable for clinical trials in treatment of patients with recurrent gynecologic cancers.

Recent advances in molecular biology and tumor immunology have resulted in identification of many tumor antigens and epitopes recognized by tumor-reactive cytotoxic T lymphocytes (CTLs). 1,2 In the field of gynecology, vaccination has been conducted with human papilloma virus (HPV)16 E7-derived peptides for HLA-A2+ patients with cervical cancer, although clinical responses have been unsatisfactory. 3-5 We previously identified a panel of antigenic peptides having the potential to induce peptide-specific and tumor-reactive CTLs in patients with epithelial cancers, 6-16 and several antigens have been shown to be expressed in gynecologic cancers and to have the potential to induce CTLs reactive to gynecologic cancers. 17

In most protocols of peptide-based vaccination, no consideration has been paid to whether or not peptide-specific CTL precursors are preexistent in cancer patients. Since priming of naive CTLs generally takes longer than boosting of primed CTLs, vaccination with peptides after confirmation of preexisting peptide-specific CTL precursors might be therapeutically beneficial because it would promptly induce peptide-specific CTLs. To put this idea into practice, we developed a new culture protocol to screen a panel of antigenic peptides with a limited number of peripheral blood mononuclear cells (PBMCs), 18 and we confirmed that peptide-specific CTL precursors can be detected in most patients with pancreatic or gastric cancer. 19,20 In this study, gynecologic cancer patients were vaccinated with peptides according to two different regimens: vaccination with predesignated peptides or vaccination with peptides to which preexisting CTL precursors in the periphery were confirmed before vaccination. Our results suggest that the latter evidence-based regimen is effective for patients with recurrent gynecologic cancers, especially cervical cancer.

 2004 Lippincott Williams & Wilkins, Inc.

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