PMID- 16365605
OWN - NLM
STAT- MEDLINE
DCOM- 20060201
LR  - 20191109
IS  - 1524-9557 (Print)
IS  - 1524-9557 (Linking)
VI  - 29
IP  - 1
DP  - 2006 Jan-Feb
TI  - Phase 2 study of the g209-2M melanoma peptide vaccine and low-dose interleukin-2 
      in advanced melanoma: Cancer and Leukemia Group B 509901.
PG  - 95-101
AB  - High-dose interleukin-2 (IL-2) is the only approved immunologic therapy for 
      advanced melanoma, but response rates are low and significant toxicities limit 
      treatment to otherwise healthy patients. g209-2M is a nanopeptide engineered to 
      mimic an epitope of the gp100 melanocyte differentiation protein that is 
      recognized in a human leukocyte antigen (HLA)-restricted manner by melanoma 
      tumor-infiltrating lymphocytes in some patients. Previous reports indicated that 
      administration of the g209-2M peptide could induce g209-reactive circulating T 
      cells in patients with melanoma and that the combination of g209-2M and high-dose 
      IL-2 might be a more active treatment than high-dose IL-2 alone. Low-dose IL-2 is 
      not active but has significant biologic effects, and because of a different 
      toxicity profile, it can be offered to most patients. The primary objective of 
      this cooperative group phase 2 study was to determine the activity of the 
      combination of g209-2M and low-dose IL-2 in advanced melanoma. Twenty-six HLA 
      appropriate patients with advanced melanoma received subcutaneous g209-2M peptide 
      once every 3 weeks and subcutaneous IL-2 (5 million IU/m) daily for 5 days during 
      the first and second weeks. Patients were monitored for tumor response, toxicity, 
      and induction of g209-reactive circulating T cells. There were no objective 
      responses. There were no toxic deaths and no grade 4 toxicities. More than half 
      of the patients experienced some grade 2 toxicity and one quarter experienced 
      grade 3 toxicity. There was no convincing evidence by enzyme-linked immunospot or 
      tetramer analysis of induction of g209-reactive circulating T cells. The 
      combination of g209-2M and low-dose IL-2 is safe and tolerable but inactive 
      against advanced melanoma. Absence of evidence of immunization raises concerns 
      for peptide-based immunization strategies with concurrent IL-2.
FAU - Roberts, John D
AU  - Roberts JD
AD  - Virginia Commonwealth University, Richmond, Virgina 23298-0037, USA. 
      john.d.roberts@vcu.edu
FAU - Niedzwiecki, Donna
AU  - Niedzwiecki D
FAU - Carson, William E
AU  - Carson WE
FAU - Chapman, Paul B
AU  - Chapman PB
FAU - Gajewski, Thomas F
AU  - Gajewski TF
FAU - Ernstoff, Marc S
AU  - Ernstoff MS
FAU - Hodi, F Stephen
AU  - Hodi FS
FAU - Shea, Christopher
AU  - Shea C
FAU - Leong, Stanley P
AU  - Leong SP
FAU - Johnson, Jeffrey
AU  - Johnson J
FAU - Zhang, Dongsheng
AU  - Zhang D
FAU - Houghton, Alan
AU  - Houghton A
FAU - Haluska, Frank G
AU  - Haluska FG
CN  - Cancer and Leukemia Group B
LA  - eng
GR  - CA04326/CA/NCI NIH HHS/United States
GR  - CA12449/CA/NCI NIH HHS/United States
GR  - CA31946/CA/NCI NIH HHS/United States
GR  - CA32291/CA/NCI NIH HHS/United States
GR  - CA33601/CA/NCI NIH HHS/United States
GR  - CA41287/CA/NCI NIH HHS/United States
GR  - CA52764/CA/NCI NIH HHS/United States
GR  - CA60138/CA/NCI NIH HHS/United States
GR  - CA77651/CA/NCI NIH HHS/United States
GR  - CA77658/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Cancer Vaccines)
RN  - 0 (Interleukin-2)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (PMEL protein, human)
RN  - 0 (Peptide Fragments)
RN  - 0 (Peptides)
RN  - 0 (g209-2M melanoma peptide)
RN  - 0 (gp100 Melanoma Antigen)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Cancer Vaccines/*administration & dosage
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Interleukin-2/*administration & dosage
MH  - Leukocytes, Mononuclear/drug effects/immunology
MH  - Male
MH  - Melanoma/immunology/*therapy
MH  - Membrane Glycoproteins/immunology/*therapeutic use
MH  - Middle Aged
MH  - Neoplasm Recurrence, Local/therapy
MH  - Peptide Fragments/immunology/*therapeutic use
MH  - Peptides
MH  - Skin Neoplasms/immunology/*therapy
MH  - gp100 Melanoma Antigen
EDAT- 2005/12/21 09:00
MHDA- 2006/02/02 09:00
CRDT- 2005/12/21 09:00
PHST- 2005/12/21 09:00 [pubmed]
PHST- 2006/02/02 09:00 [medline]
PHST- 2005/12/21 09:00 [entrez]
AID - 00002371-200601000-00011 [pii]
AID - 10.1097/01.cji.0000195295.74104.ad [doi]
PST - ppublish
SO  - J Immunother. 2006 Jan-Feb;29(1):95-101. doi: 10.1097/01.cji.0000195295.74104.ad.