Enhanced viral and tumor immunity with intranodal injection of canary pox viruses expressing the melanoma antigen, gp100.

Abstract

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.

• Authors: David E Spaner, Igor Astsaturov, Thorsten Vogel, Teresa Petrella, Ileana Elias, Susan Burdett-Radoux, Shailendra Verma, Neill Iscoe, Paul Hamilton, Neil L Berinstein
• Journal: Cancer (Cancer) Vol. 106 Issue 4 Pg. 890-9 (Feb 15 2006) ISSN: 0008-543X [Print] United States
• PMID: 16404742 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2006 American Cancer Society.

Chemical References

• Cancer Vaccines
• HLA-A Antigens
• HLA-A*02:01 antigen
• HLA-A2 Antigen
• Membrane Glycoproteins
• Neoplasm Proteins
• PMEL protein, human
• Tetanus Toxoid
• gp100 Melanoma Antigen

Topics

• Adult
• Aged
• CD8-Positive T-Lymphocytes (immunology)
• Canarypox virus (genetics, immunology)
• Cancer Vaccines (immunology)
• Enzyme-Linked Immunosorbent Assay
• Female
• Genetic Vectors
• HLA-A Antigens
• HLA-A2 Antigen
• Humans
• Injections, Subcutaneous
• Lymphatic Metastasis (immunology)
• Male
• Melanoma (immunology, therapy)
• Membrane Glycoproteins (immunology)
• Middle Aged
• Neoplasm Proteins (immunology)
• Skin Neoplasms (immunology, therapy)
• Tetanus Toxoid
• gp100 Melanoma Antigen