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.

Abstract

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: 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 26 Issue 27 Pg. 4418-25 (Sep 20 2008) ISSN: 1527-7755 [Electronic] United States
• PMID: 18802154 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Cancer Vaccines
• Epitopes, T-Lymphocyte
• IDM 2101

Topics

• Adult
• Aged
• Aged, 80 and over
• Cancer Vaccines (immunology, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (immunology, prevention & control, secondary)
• Epitopes, T-Lymphocyte (immunology)
• Female
• Humans
• Lung Neoplasms (immunology, prevention & control)
• Male
• Middle Aged
• Remission Induction
• T-Lymphocytes, Cytotoxic (immunology)