PMID- 16551861
OWN - NLM
STAT- MEDLINE
DCOM- 20061127
LR  - 20161124
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 12
IP  - 6
DP  - 2006 Mar 15
TI  - A phase I trial of vaccination of CA9-derived peptides for HLA-A24-positive 
      patients with cytokine-refractory metastatic renal cell carcinoma.
PG  - 1768-75
AB  - PURPOSE: A phase I peptide vaccination trial was done in patients with 
      progressive cytokine-refractory metastatic renal cell carcinoma (RCC) to assess 
      both the toxicity and capability to induce immune responses of three peptides 
      (CA9p219-227, p288-296, and p323-331) derived from CA9, a tumor-associated 
      antigen ubiquitously expressed in RCC. EXPERIMENTAL DESIGN: Twenty-three patients 
      positive for human leukocyte antigen (HLA)-A24 with histologically confirmed RCC 
      were enrolled. Eligibility included progressive disease after standard cytokine 
      therapy with interleukin-2 and/or IFN-alpha. Patients were vaccinated s.c. with 
      the three peptides emulsified in incomplete Freund's adjuvant at 2-week 
      intervals. Pre- and post-vaccination blood samples were obtained for toxicity 
      assessment and immunologic studies. Patients were monitored for clinical 
      responses on a 3-monthly basis. RESULTS: Vaccinations were well tolerated without 
      any major adverse event. Most of the patients developed peptide-specific CTLs 
      and/or immunoglobulin G reactive to the peptides after the 6th or 9th 
      vaccination, followed by a gradual increase in both CTL frequency and levels of 
      peptide-reactive serum IgG. Three patients with multiple lung metastases showed 
      partial responses with disappearance and shrinking of metastatic lesions. 
      Additionally, stable disease for >6 months was observed in six patients (median 
      duration, 12.2 months). Moreover, the median survival time of all patients who 
      were progressive at trial enrollment after failing immunotherapy was 21.0 months 
      (5-35 months). CONCLUSIONS: These results suggest that vaccination of these 
      peptides is safe and recommended for further trials for HLA-A24-positive 
      metastatic RCC patients.
FAU - Uemura, Hirotsugu
AU  - Uemura H
AD  - Department of Urology, Kinki University School of Medicine, Osaka, Japan. 
      huemura@med.kindai.ac.jp
FAU - Fujimoto, Kiyohide
AU  - Fujimoto K
FAU - Tanaka, Motoyoshi
AU  - Tanaka M
FAU - Yoshikawa, Motoyoshi
AU  - Yoshikawa M
FAU - Hirao, Yoshihiko
AU  - Hirao Y
FAU - Uejima, Shigeya
AU  - Uejima S
FAU - Yoshikawa, Kazuhiro
AU  - Yoshikawa K
FAU - Itoh, Kyogo
AU  - Itoh K
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Cytokines)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A24 Antigen)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Vaccines, Subunit)
RN  - EC 4.2.1.1 (CA9 protein, human)
RN  - EC 4.2.1.1 (Carbonic Anhydrase IX)
RN  - EC 4.2.1.1 (Carbonic Anhydrases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antigens, Neoplasm/*immunology
MH  - Cancer Vaccines/adverse effects/immunology/*therapeutic use
MH  - Carbonic Anhydrase IX
MH  - Carbonic Anhydrases/*immunology
MH  - Carcinoma, Renal Cell/*drug therapy/immunology/mortality
MH  - Cytokines/therapeutic use
MH  - Drug Resistance, Neoplasm
MH  - Fatigue/chemically induced
MH  - Female
MH  - Fever/chemically induced
MH  - HLA-A Antigens/*immunology
MH  - HLA-A24 Antigen
MH  - Humans
MH  - Immunity, Cellular/drug effects
MH  - Immunoglobulin G/blood
MH  - Kidney Neoplasms/*drug therapy/immunology/mortality
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Survival Rate
MH  - T-Lymphocytes, Cytotoxic/drug effects/immunology
MH  - Treatment Outcome
MH  - Vaccines, Subunit/adverse effects/immunology/therapeutic use
EDAT- 2006/03/23 09:00
MHDA- 2006/12/09 09:00
CRDT- 2006/03/23 09:00
PHST- 2006/03/23 09:00 [pubmed]
PHST- 2006/12/09 09:00 [medline]
PHST- 2006/03/23 09:00 [entrez]
AID - 12/6/1768 [pii]
AID - 10.1158/1078-0432.CCR-05-2253 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2006 Mar 15;12(6):1768-75. doi: 10.1158/1078-0432.CCR-05-2253.