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 CTP3 7, a synthetic peptide corresponding to the COOH-terminal peptide (CTP ) of beta-human chorionic gonadotropin (beta-hCG) conjugated to diphth eria toroid, 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. i njection of a fixed dose of CTP37 and escalating doses of CRL 1005. Do ses of CRL 1005 adjuvant as high as 75 mg were administered with 1 mg of CTP37 without evidence of significant local or systemic toxicity. I mmunizations resulted in the production of IgG antibody to beta-hCG, C RL 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, h CG, and diphtheria toxoid. Responding PBMCs specifically secreted the T(H)1-associated cytokines IFN-gamma and interleukin (IL)-2 as well as the T(H)2-associated IL-5 and IL-10. Increased expression of IFN gamm a and IL-5 mRNAs by PBMCs 4 h after immunization was also observed. CR L 1005 administered with CTP37 in aqueous solution is well tolerated. The CTP37-CRL 1005 subunit vaccine has the capacity to stimulate poten tially beneficial humoral and cellular immune responses in patients wi th advanced cancer.