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.
OBJECTIVE
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).


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).


CONCLUSIONS
IDM-2101 was well tolerated, and evidence of efficacy was suggested.
Barve
Minal
M
Mary Crowley Cancer Research Centers, Dallas, TX, USA.
Bender
James
J
Senzer
Neil
N
Cunningham
Casey
C
Greco
F Anthony
FA
McCune
David
D
Steis
Ronald
R
Khong
Hung
H
Richards
Donald
D
Stephenson
Joe
J
Ganesa
Prasanthi
P
Nemunaitis
Jackie
J
Ishioka
Glenn
G
Pappen
Beena
B
Nemunaitis
Michael
M
Morse
Michael
M
Mills
Bonnie
B
Maples
Phillip B
PB
Sherman
Jeffrey
J
Nemunaitis
John J
JJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology* / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; C532151:IDM 2101