Immune responses detected in urothelial carcinoma patients after vaccination with NY-ESO-1 protein plus BCG and GM-CSF.
Urothelial carcinoma of the bladder is a solid tumor entity for which the immunomodulatory agent Bacillus-Calmette Guerin (BCG) has been shown to have substantial efficacy with approximately 90% cure rates in select patients with superficial disease. Immune-based therapies for patients with more invasive disease do not currently exist. We previously showed that invasive urothelial carcinomas express the NY-ESO-1 tumor antigen. Here we evaluated the safety and immunogenicity of a recombinant NY-ESO-1 protein vaccine, which was administered with granulocyte macrophage colony-stimulating factor and BCG as immunologic adjuvants in a cohort of urothelial carcinoma patients. Sixty-two urothelial carcinoma patients were screened for enrollment onto the vaccine clinical trial and 6 patients met all eligibility criteria to receive vaccination. Patients with localized disease underwent surgical removal of their bladders as treatment for their disease. Tumor tissues were tested for NY-ESO-1 expression and eligible patients, shown to have NY-ESO-1 tumors, were vaccinated in the postoperative setting. Peripheral blood samples were analyzed for vaccine-induced antibody and T-cell responses. The vaccine regimen was well tolerated with only mild injection site reactions. NY-ESO-1-specific antibody responses were induced in 5/6 patients whereas CD8 T-cell responses occurred in 1/6 patients and CD4 T-cell responses were found in 6/6 patients. This study demonstrates safety and feasibility of the NY-ESO-1 recombinant protein in combination with BCG and granulocyte macrophage colony-stimulating factor to induce predominantly antibody and CD4 T-cell responses in urothelial carcinoma patients. Induction of higher frequency of CD8 T-cell responses may be possible in clinical trials implementing NY-ESO-1 vaccination in combination with other immunomodulatory agents.
Sharma
Padmanee
P
Department of Genitourinary Medical Oncology, M. D. Anderson Cancer Center, University of Texas, Houston, TX 77030, USA. Padsharma@mdanderson.org
Bajorin
Dean F
DF
Jungbluth
Achim A
AA
Herr
Harry
H
Old
Lloyd J
LJ
Gnjatic
Sacha
S
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000917:Antibody Formation; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001500:BCG Vaccine / Q000009:adverse effects / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology; D002277:Carcinoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D018604:Epitope Mapping; D000939:Epitopes; D004890:Erythema / Q000209:etiology / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D019459:Urothelium / Q000473:pathology
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D001500:BCG Vaccine; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D000939:Epitopes; D008565:Membrane Proteins; D011994:Recombinant Proteins; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor