Enhanced viral and tumor immunity with intranodal injection of canary pox viruses expressing the melanoma antigen, gp100.
BACKGROUND
The route of administration and extent of helper T-cell activation are factors that are likely to be important for the development of effective cancer vaccines. In order to optimize CD8(+) cytotoxic T-lymphocyte (CTL) responses, the immunologic effects of direct lymph node (LN) injections of canary pox virus (ALVAC) vectors (expressing the melanoma antigen, gp100) and immunogenic gp100 peptides, along with concomitant injections of the helper adjuvant, tetanus toxoid, were studied in high-risk HLA-A*0201(+) patients.


METHODS
Forty-two patients were vaccinated using six different protocols. Twenty-three patients were 'primed' with ALVAC(2)-gp100m and 'boosted' with gp100 peptides, either subcutaneously or into an LN. Intranodal (IN) peptides, alone, were administered to six patients. Thirteen patients were given tetanus toxoid initially, and with each gp100 vaccination. Toxicity was recorded and immunologic responses were determined in 35 patients by enzyme-linked immunospot (ELISPOT) and gp100-tetramer binding assays and anti-ALVAC(2) enzyme-linked immunosorbent assays (ELISAs).


RESULTS
All vaccine protocols were tolerated well. Using stringent criteria for immunologic response, 8 of 18 patients responded to the viral vaccines, in striking contrast to peptides only (0 of 6 patients) or with help in trans from tetanus-reactive T-cells (1 of 11 patients). Changes in gp100-reactive CTL frequencies and ALVAC antibodies were greatest when viruses were injected directly into LNs.


CONCLUSIONS
IN injections of ALVAC(2)-gp100m viruses are feasible, safe, and may be a superior method of vaccination in humans. CTL responses to this vaccine were not enhanced by tetanus toxoid.
Spaner
David E
DE
Division of Molecular and Cellular Biology, Research Institute, Sunnybrook and Women's College Health Sciences Center, Toronto, Canada. spanerd@srcl.sunnybrook.utoronto.ca
Astsaturov
Igor
I
Vogel
Thorsten
T
Petrella
Teresa
T
Elias
Ileana
I
Burdett-Radoux
Susan
S
Verma
Shailendra
S
Iscoe
Neill
N
Hamilton
Paul
P
Berinstein
Neil L
NL
D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D028121:Canarypox virus / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005822:Genetic Vectors; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D006801:Humans; D007279:Injections, Subcutaneous; D008207:Lymphatic Metastasis / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000276:immunology*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology*; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D013745:Tetanus Toxoid; D058951:gp100 Melanoma Antigen
D019496:Cancer Vaccines; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D013745:Tetanus Toxoid; D058951:gp100 Melanoma Antigen