This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Barve, M. Articles by Nemunaitis, J. J. Search for Related Content PubMed PubMed Citation Articles by Barve, M. Articles by Nemunaitis, J. J. Social Bookmarking                            What's this?

Induction of Immune Responses and Clinical Efficacy in a Phase II Trial of IDM-2101, a 10-Epitope Cytotoxic T-Lymphocyte Vaccine, in Metastatic Non–Small-Cell Lung Cancer

Minal Barve, James Bender, Neil Senzer, Casey Cunningham, F. Anthony Greco, David McCune, Ronald Steis, Hung Khong, Donald Richards, Joe Stephenson, Prasanthi Ganesa, Jackie Nemunaitis, Glenn Ishioka, Beena Pappen, Michael Nemunaitis, Michael Morse, Bonnie Mills, Phillip B. Maples, Jeffrey Sherman, John J. Nemunaitis

From the Mary Crowley Cancer Research Centers; Baylor Sammons Cancer Center; Gradalis Inc; and Texas Oncology Physicians Association, Dallas; Tyler Cancer Center, Tyler, TX; IDM Pharma Inc, Irvine; Pharmexa-Epimmune, San Diego, CA; Sarah Cannon Cancer Center, Nashville, TN; Madigan Army Medical Center, Tacoma WA; Atlanta Cancer Care, Roswell, GA; University of South Alabama, Mitchell Cancer Institute, Mobile, AL; Cancer Center of the Carolinas, Greenville, SC; and Duke University Medical Center, Durham, NC

Corresponding author: John J. Nemunaitis, MD, 1700 Pacific Ave, Suite 1100, Dallas, TX 75201; e-mail: jnemunaitis{at}marycrowley.org

Purpose Generation of broad cytotoxic T-lymphocyte responses against multiple epitopes and tumor-associated antigens (TAAs) may provide effective immunotherapy in patients with cancer. We evaluated a single-vial peptide vaccine consisting of nine HLA-A2 supertype-binding epitopes (two native and seven analog epitopes modified for optimal HLA binding or T-cell receptor stimulation) covering five TAAs and the universal helper pan-DR epitope, formulated as a stable emulsion with incomplete Freund's adjuvant (Montanide ISA 51; Seppic SA, Paris, France). The clinical efficacy, safety, and multiepitope immunogenicity of IDM-2101 was evaluated in patients with stage IIIB or IV non–small-cell lung cancer (NSCLC).

Patients and Methods A total of 63 patients were enrolled who were positive for HLA-A2. End points included survival, safety, and immune response. IDM-2101 (previously EP-2101) was administered every 3 weeks for the first 15 weeks, then every 2 months through year 1, then quarterly through year 2, for a total of 13 doses. Epitope-specific cytotoxic and helper T-lymphocyte immunogenic responses were measured by the interferon gamma enzyme-linked immunosorbent spot assay.

Results No significant adverse events were noted. Low-grade erythema and pain at the injection site were the most common adverse effects. One-year survival in the treated patients was 60%, and median survival was 17.3 months. One complete and one partial response were identified. Survival was longer in patients demonstrating an immune response to epitope peptides (P < .001).

Conclusion IDM-2101 was well tolerated, and evidence of efficacy was suggested.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical trial information can be found for the following: NCT00054899 [ClinicalTrials.gov] .

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?