Pilot study of a dual gene recombinant avipox vaccine containing both carcinoembryonic antigen (CEA) and B7.1 transgenes in patients with recurrent CEA-expressing adenocarcinomas.
Coordinated presentation of antigen and costimulatory molecules has been shown to result in the induction of an antigen-specific T-cell response rather than the development of anergy. This study evaluated the vaccine ALVAC-CEA B7.1, a canary pox virus that has been engineered to encode the gene for the tumor-associated antigen carcinoembryonic antigen (CEA) and B7.1, a T-cell costimulatory molecule. Patients with CEA-expressing tumors were immunized with 2.5 x 10(7) (n = 3), 1.0 x 10(8) (n = 6), and 4.5 x 10(8) (n = 30) plaque-forming units intradermally every other week for 8 weeks. Patients with stable or responding disease received monthly boost injections. Biopsies of vaccine sites were obtained 48 h after vaccination to evaluate leukocytic infiltration and CEA expression. Induction of CEA-specific T-cell precursors was assessed by an ELISPOT assay looking for the production of IFN-gamma. Therapy was well tolerated, without significant toxicity attributable to vaccine. All patients had evidence of leukocytic infiltration and CEA expression in vaccine biopsy sites. Six patients with elevated serum CEA values at baseline had declines in their levels lasting 4-12 weeks. These patients all had stable disease after four vaccinations. After four vaccinations, patients who were HLA-A-2-positive demonstrated increases in their CEA-specific T-cell precursor frequencies to a CEA-A2-binding peptide from baseline. The number of prior chemotherapy regimens was inversely correlated with the ability to generate a T-cell response. ALVAC-CEA B7.1 is safe in patients with advanced, recurrent adenocarcinomas that express CEA, and it is associated with the induction of a CEA-specific T-cell response.
von Mehren
M
M
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. m_vonmehren@fccc.edu
Arlen
P
P
Tsang
K Y
KY
Rogatko
A
A
Meropol
N
N
Cooper
H S
HS
Davey
M
M
McLaughlin
S
S
Schlom
J
J
Weiner
L M
LM
D000230:Adenocarcinoma / Q000276:immunology / Q000628:therapy*; D000328:Adult; D000368:Aged; D018150:Avipoxvirus / Q000235:genetics*; D018122:B7-1 Antigen / Q000235:genetics* / Q000633:toxicity; D001706:Biopsy; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D010865:Pilot Projects; D012044:Regression Analysis; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000627:therapeutic use* / Q000633:toxicity
D018122:B7-1 Antigen; D002272:Carcinoembryonic Antigen; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; D007371:Interferon-gamma