Inability to immunize patients with metastatic melanoma using plasmid DNA encoding the gp100 melanoma-melanocyte antigen.
Immunization with plasmid DNA represents a theoretically attractive method for increasing T cell responses against cancer antigens. We administered plasmid DNA encoding the gp100 melanoma-melanocyte differentiation antigen to 22 patients with metastatic melanoma and evaluated immunologic and clinical responses. Patients were randomized to receive plasmid DNA either intradermally (n = 10) or intramuscularly (n = 12). One patient (4.5%) exhibited a partial response of several subcentimeter cutaneous nodules. All other patients had progressive disease. Of 13 patients with cells available before and after immunization, no patient exhibited evidence of the development of anti-gp100 cell responses using in vitro boost assays. The same assays were capable of demonstrating immunologic precursors after immunization with fowl poxvirus encoding gp100 or with gp100 peptides. We were thus unable to demonstrate significant clinical or immunologic responses to plasmid DNA encoding the "self" nonmutated gp100 tumor antigen.
Rosenberg
Steven A
SA
Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1502, USA. sar@nih.gov
Yang
James C
JC
Sherry
Richard M
RM
Hwu
Patrick
P
Topalian
Suzanne L
SL
Schwartzentruber
Douglas J
DJ
Restifo
Nicholas P
NP
Haworth
Leah R
LR
Seipp
Claudia A
CA
Freezer
Linda J
LJ
Morton
Kathleen E
KE
Mavroukakis
Sharon A
SA
White
Donald E
DE
D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D010957:Plasmids / Q000008:administration & dosage; D017211:Treatment Failure; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D058951:gp100 Melanoma Antigen
D019496:Cancer Vaccines; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D019444:Vaccines, DNA; D058951:gp100 Melanoma Antigen