Effects of a beta-human chorionic gonadotropin subunit immunogen administered in aqueous solution with a novel nonionic block copolymer adjuvant in patients with advanced cancer.
The clinical and immunological effects of a vaccine consisting of CTP37, a synthetic peptide corresponding to the COOH-terminal peptide (CTP) of beta-human chorionic gonadotropin (beta-hCG) conjugated to diphtheria toxoid, combined with CRL 1005, a novel synthetic nonionic block copolymer adjuvant, were examined. Twenty-one patients with metastatic, nontrophoblastic cancers received up to four immunizations by i.m. injection of a fixed dose of CTP37 and escalating doses of CRL 1005. Doses of CRL 1005 adjuvant as high as 75 mg were administered with 1 mg of CTP37 without evidence of significant local or systemic toxicity. Immunizations resulted in the production of IgG antibody to beta-hCG. CRL 1005 doses of 3-25 mg appeared to be optimal for antibody induction. Immunizations also resulted in increases in the cellular response of peripheral blood mononuclear cells (PBMCs) to the unconjugated CTP, hCG, and diphtheria toxoid. Responding PBMCs specifically secreted the TH1-associated cytokines IFN-gamma and interleukin (IL)-2 as well as the TH2-associated IL-5 and IL-10. Increased expression of IFN gamma and IL-5 mRNAs by PBMCs 4 h after immunization was also observed. CRL 1005 administered with CTP37 in aqueous solution is well tolerated. The CTP37-CRL 1005 subunit vaccine has the capacity to stimulate potentially beneficial humoral and cellular immune responses in patients with advanced cancer.
Triozzi
P L
PL
The Ohio State University Comprehensive Cancer Center, 410 West 10th Ave, Columbus, Ohio 43210, USA.
Stevens
V C
VC
Aldrich
W
W
Powell
J
J
Todd
C W
CW
Newman
M J
MJ
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D000328:Adult; D000368:Aged; D000917:Antibody Formation; D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004168:Diphtheria Toxoid / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D010426:Pentosan Sulfuric Polyester / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011108:Polymers; D012996:Solutions; D018417:Th1 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; C113154:CRL 1005; C117350:CTP37 peptide; D006063:Chorionic Gonadotropin; D018997:Chorionic Gonadotropin, beta Subunit, Human; D004168:Diphtheria Toxoid; D007074:Immunoglobulin G; D007376:Interleukin-2; D015848:Interleukin-5; D011108:Polymers; D012996:Solutions; D010426:Pentosan Sulfuric Polyester; D007371:Interferon-gamma