Immune responses detected in urothelial carcinoma patients after vaccination with NY-ESO-1 protein plus BCG and GM-CSF Journal Article
| Authors: | Sharma, P.; Bajorin, D. F.; Jungbluth, A. A.; Herr, H.; Old, L. J.; Gnjatic, S. |
| Article Title: | Immune responses detected in urothelial carcinoma patients after vaccination with NY-ESO-1 protein plus BCG and GM-CSF |
| Abstract: | 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. |
| Keywords: | survival; clinical trial; peptide; antigens; radical cystectomy; memory; vaccine; expression; ny-eso-1; t-cell responses; bladder-cancer; tumor-infiltrating lymphocytes; t-cells; antibody-responses; superficial; urothelial carcinoma patients |
| Journal Title: | Journal of Immunotherapy |
| Volume: | 31 |
| Issue: | 9 |
| ISSN: | 1524-9557 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2008-11-01 |
| Start Page: | 849 |
| End Page: | 857 |
| Language: | English |
| ACCESSION: | WOS:000260358800007 |
| DOI: | 10.1097/CJI.0b013e3181891574 |
| PROVIDER: | wos |
| PUBMED: | 18833002 |
| Notes: | --- - Article - "Source: Wos" |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work